Advanced Pharmacotherapy III Exam 3

•You are an ambulatory care pharmacist working in a family medicine clinic. Today you are serving as a drug information resource for five family medicine residents. One of the residents, Dr. Ihartfarmasee comes over to see what you think of his plan before he presents it to his attending physician. •Dr. Ihartfarmasee saw an 8-year-old, female patient (GL) who was accompanied by her brother, sister and her mothers. GL complained of a sore throat and a lot of pain when she swallowed. GL rated her pain as an 8/10. •Dr. Ihartfarmasee had rapid antigen detection tests performed on all family members, GL's and her brother's were the only positive RADTs. •Dr. Ihartfarmasee is planning to prescribe azithromycin x10 days for GL and her brother for treatment and azithromycin x 3 days for GL's sister and mothers for prophylaxis. •What are your thoughts about Dr. Ihartfarmasee's plan? •How would you share your thoughts with him?

1. Pharyngitis, amoxicillin is first line unless allergy, antibiotics for prophylaxis weird 2. Only one person needs ABX

What are the Predisposing Risk Factors for a UTI?

1. Pre-menopausal Women •Sexual intercourse •Diaphragm, esp with spermicide •History of UTI •Genetic component •*Diabetes* 2. Post-menopausal Women •Estrogen deficiency •History of UTI •Urinary catheterization •*Urinary incontinence* •*Function or mental impairment* 3. Men/Women with Structural Abnormalities •Congenital anomalies •Benign prostate hypertrophy

What is the Minor Duke Criteria? Don't need to memorize

1. Predisposition, predisposing heart condition, or IDU 2. Fever, temperature >38°C 3. Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions 4. Immunological phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor 5. Microbiological evidence: positive blood culture but does not meet a major criterion as noted above (excludes single positive cultures for coagulase negative staphylococci and organisms that do not cause endocarditis) or serological evidence of active infection with organism consistent with IE 6. Echocardiographic minor criteria eliminated

What is the treatment for Pyelonephritis?

1. Preferred Ciprofloxacin 500 mg PO BID x 7 days (Can only use if resistance < 10%) Ciprofloxacin 1000 mg ER qday X 7 days (OR Levofloxacin 750 mg PO x 5 days) (Can only use if resistance < 10%) Ceftriaxone 1 gm IV q day OR AG q day (Until C&S back) 2. Alternative Sulfamethoxazole/trimethoprim 160/800 PO BID x 14 days (Definitive tmt only) Beta-lactams 10 - 14 days (Definitive tmt only)

What are the treatments for uncomplicated cystitis?

1. Preferred Nitrofurantoin 100 mg PO BID x 5 days Sulfamethoxazole/trimethoprim 160/800 PO BID x 3 days (Can only use if resistance rates < 20%) Fosfomycin 3 gm PO once 2. Alternative Fluoroquinolones x 3 days (Should be reserved Can only use if resistance < 10%) Beta-lactams x 3 - 7 days (Inferior efficacy and more adverse effects compared to first line)

What are the PCP Treatment Options?

1. Preferred: TMP/SMX 15 - 20 mg/kg/day in 3-4 divided doses (dosed on trimethoprim component) for 21 days If severe PCP (Pa02 < 70 mmHg) , need to add steroid 2. Alternative: Pentamidine IV Primaquine + clindamycin Dapsone + trimethoprim Atovaquone

What is the Rhinosinusitis presentation and pathogens?

1. Presentation •Sinus pressure •Headache •Postnasal drainage •Nasal congestion •Nasal obstruction •Discolored nasal discharge •Sore throat •Fever 2. Pathogens •Viral (most cases) •Bacterial (1-2%) •Streptococcus pneumoniae •Nontypeable Haemophilus influenzae •Moraxella catarrhalis

What are the three kinds of Peritonitis?

1. Primary Spontaneous bacterial peritonitis develops in the peritoneal cavity without bacterial source within the abdomen 2. Secondary Fecal contamination within the abdomen caused by perforation, postoperative peritonitis or trauma 3. Tertiary Infection that persists or recurs at least 48 hours after initial peritonitis treatment Associated with higher morbidity and mortality

What is the Toxo Primary and Secondary PPX?

1. Primary prevention All patients should be tested for toxo IgG soon after HIV diagnosis Start when CD4 count < 100 AND IgG + Preferred: TMP/SMX 1 DS daily Alternatives: TMP/SMX DS TIW or SS daily, dapsone + pyrimethamine + leucovorin, atovaquone +/- pyrimethamine + leucovorin Cannot use dapsone alone or aerosolized pentamidine for toxo ppx 2. Secondary prevention Same as agents toxo treatment Sulfadiazine + pyrimethamine + leucovorin Will need to restart if ever CD4 count < 200 When to stop ppx: Primary ppx: Continue either primary ppx until CD4 count > 200 for 3 months OR CD4 count 100 - 200 and undetectable HIV RNA for 3 - 6 months Secondary ppx: Successfully completed initial therapy AND remain free of signs and symptoms AND CD4 count >200 for >6 months in response to ART

What is the PCP Primary and Secondary PPX?

1. Primary prevention CD4 count < 200 or CD4 % < 14 CD4 count 200 - 250 if cannot start ART + CD4 count monitoring unavailable Preferred: TMP/SMX 1 DS daily or 1 SS daily or 1 DS MWF Alternatives: atovaquone, dapsone, dapsone + pyrimethamine + leucovorin, aerosolized pentamidine 2. Secondary prevention= Same as primary ppx Continue either primary or secondary ppx until CD4 count > 200 for 3 months OR CD4 count 100 - 200 and undetectable HIV RNA for 3 - 6 months

What is the MAC primary and secondary PPX?

1. Primary prevention Start when CD4 < 50 in absence of ART Preferred: Azithromycin or clarithromycin Alternative: Rifabutin Lots of drug interactions 2. Secondary prevention Same as primary ppx Will need to restart if ever CD4 count < 100 When to stop PPX: Primary: Start of effective ART Secondary: Completed at least 12 months of therapy AND CD4 count > 100 for at least 6 months in response to ART AND no signs/symptoms of MAC disease

What are the OI Treatment Principles?

1. Primary prophylaxis (ppx) (does NOT have disease): Prevent infection BEFORE patient has the disease 2. Secondary ppx (has/had the disease) Prevent relapse or re-infection AFTER patient has completed treatment for the disease Also referred to as chronic maintenance Treat OI or HIV first? IRIS = immune reconstitution inflammatory syndrome *Treat OI first* Cryptococcal meningitis and TB CD4 count less than threshold = patient at risk for various OIs Infected/diagnosed with OI? *No- start primary prevention* Yes- Start treatment, once they have Completed treatment course AND improving, start *secondary ppx* If not, re-evaluate

What is the candida PPX?

1. Primary: None 2. Secondary Only recommended when recurrences are frequent or severe Oropharyngeal - itraconazole or posaconazole Esophageal - voriconazole, isavuconazole, echinocandins, amphotericin B When to stop PPX: Secondary ppx only indicated in specific cases Consider stopping when CD4 count > 200 following initiation ART

What are the NNRTIS/Contraindications?

1. Proton Pump Inhibitors (PPIs) with RPV 2. Clopidogrel with ETR 3. Anticonvulsants (phenobarbital/phenytoin/CBZ) with ETR, RPV, DOR 4. Voriconazole with EFV (at std doses) 5. Rifampin/Rifapentine with NVP, ETR, RPV, DOR 6. Bedaquiline with EFV and ETR 7. St Johns Wort with EFV, NVP, ETR, RPV, DOR

What are the main gram negative bacteria?

1. Pseudomonas aeruginosa 2. Acinetobacter baumannii 3. ESBL (Extended spectrum beta-lactamase) producing organisms 4. CRE (Carbapenem resistant Enterobacterales)/KPC (carbapenem resistant K. pneumoniae)

What are the HPV Vaccines?

1. Quad valent - Gardisil 6, 11, 16 and 18 2. 9 valent - Gardisil 9 6, 11, 16 and 18 (same as quad) 31, 33, 45, 52 and 58 (oncogenic HPV)

What are the susceptibility testings?

1. Quantitative Broth dilution -Increasing antibiotic concentration in tubes with known amount of bacteria -Wait 18-24 hours -Determine MIC and MBC 2. Qualitative- does not give you MIC Disc diffusion

*What are the Primary Adverse Effects of INSTIs?*

1. Raltegravir (RAL) Headache, insomnia, CPK elevations, muscle weakness, rash, nausea, diarrhea, depression, weight gain *can be used in infants from birth, available as a chewable tablet* 2. Elvitegravir (EVG) Nausea, diarrhea, headache, depression *take with food* 3. Dolutegravir (DTG) Insomnia, headache, weight gain, hepatotoxicity, depression *high genetic barrier to resistance, BID dosing used when taking concomitant potent UGT1A1/CYP3A inducers or pt has prior INSTI resistance-associated mutations* 4. Bictegravir (BIC) Diarrhea, weight gain, nausea and headache *high genetic barrier to resistance*

What are teh Two regimen classifications for ARV-naive patients?

1. Recommended Initial Regimens for Most People with HIV 2. Recommended Initial Regimens in CertainClinical Situations

What is the Rhinosinusitis Supportive Care?

1. Recommended Symptomatic Treatments •Analgesics •Saline nasal irrigation •Intranasal glucocorticoids (allergic rhinitis) 2. No evidence to support use of: •Intranasal saline spray •Oral decongestants •Intranasal decongestants •Antihistamines •Mucolytics

What are the Recommended and alternative treatment options for Bacterial Vaginosis?

1. Recommended: Metronidazole 500 mg q 12 hr x 7 days Alt: Tinidazole 2 g daily for 2 days 2. Recommended: Metronidazole gel 0.75% One 5 g applicator intravaginally daily for 5 days Alt: Tinidazole 1 g daily for 5 days 3. Recommended: Clindamycin cream 2% One 5 g applicator intravaginally daily for 5 days Alt: Clindamycin 300 mg PO q 12 hr for 7 days Alt: Clindamycin ovules 100 mg intravaginally at bedtime for 3 days

How is Histoplasmosis diagnosed and treated?

1. Risk factors Severe immunosuppression 2. Diagnosis Complement fixation titers Antigen test 3. Treatment Mild/moderate: no tmt OR itraconazole Disseminated or moderate/severe pulm: AmB then itraconazole

What are the Differences between PK Boosters Ritonavir versus Cobicistat?

1. Ritonavir Adverse effects: None DDIs: CYP3A4/2D6 inhibition + CYP 1A2, 2B6 2C8, 2C9, 2C19 and UGT1A1 induction Potential for resistance: Possible emergence of mutations in HIV-1 protease gene Pill burden: Greater; co-formulation with lopinavir (Kaletra®) only 2. Cobicistat (Tybost®) Adverse effects: ↑ Renal considerations (increased SCr/eGFR; not aGFR) DDIs: CYP3A4 inhibition (major) + CYP2D6 inhibition (minor) Potential for resistance: No antiviral activity/reduced risk for resistance Pill burden: Less pill burden (co-formulations Evotaz®, Prezcobix®, Stribild®, Genvoya® and Symtuza®)

•CC: Increased irritability and right ear pain •HPI: a 22-month-old female presents to her primary care provider with a 2-day history of rhinorrhea and a 1 day history of increased irritability, fever (up to 101.5 F per mother), and right ear tugging. Mother denies child has had any vomiting or diarrhea. •PMH: Two episodes of AOM, with last episode 6 months ago •Surgical Hx: none •SH: lives with mother, father. Pt attends daycare 2 days/wk and stays at home with maternal grandfather 3 days/week. •NKA •Home medications: •Vitamin D drops 600 IU/day Up to date with immunizations •Vitals (while crying): temp 100.7 F, HR 140 bpm, RR 35, BP 100/57, ht 31 inches, wt 23.4 lbs •General: fussy, but consolable by Mother, well appearing •HEENT: moist mucous membranes, normal conjunctiva, clear rhinorrhea, moderate bulging and erythema of right tympanic membrane with middle ear effusion •Pulm: normal •CV: normal •Abdominal: normal •GU: normal •Neuro: normal •Extremities: normal •Assessment: 1. What is (are) the most likely bacteria responsible for this patient's infection? 2. Would you classify this patient as severe or non-severe? •Plan: 3. Select an appropriate regimen (drug, dose, duration) for this patient 4. Make sure to include appropriate monitoring parameters

1. Acute Otitis Media 50-60% nontypeable Haemophilus influenzae (NTHi) 15-25% Streptococcus pneumoniae 12-15% Moraxella catarrhalis 2. Non-severe 3. Amoxicillin. The dose is 90 mg/kg/day divided into two doses. MAX: 3g/day x10 days High dose for resistant strep pneumo 4. Relief of symptoms

What are Acute Otitis Media, Rhinosinusitis, Pharyngitis, Bronchitis caused by?

1. Acute Otitis Media oto- "ear" itis-"inflammation" media- "middle" 40-75% viral 2. Rhinosinusitis Inflammation or infection of the mucosa of the nasal passages and at least one of the paranasal sinuses 1-2% bacterial 3. Pharyngitis Inflammation or infection of the oropharynx and/or nasopharynx "sore throat" ~40% viral 4. Bronchitis lower respiratory tract infection involving the large airways (bronchi) > 90% viral 1-10% bacterial

•MA is a 22-year-old gender nonbinary person living in Yakima, WA. They developed a cough 5 days ago. They don't think it's from the smoke because they've never had a cough before during smoky summers in central Washington. They also have some sputum production, mild fever and headache. •COVID-19 Rapid test: Negative •PMH: none •Current medications: testosterone 20mg Q week •What is the most likely diagnosis for MA? •What treatment do you recommend?

1. Acute Viral Bronchitis 2. Symptomatic management 2-3 weeks

What are the other two classifications of bacteria?

1. Anaerobes - Gram negative, i.e B. fragilis - Gram positive, i.e. Peptostreptococci 2. Atypical organisms

How do you interpret the TPP?

1. Anaerobic bottle turns positive first, follow the anaerobic flow chart based on time it turned positive to figure out what bacteria it is <18 hours= Enterobacteriacae >18 hours= Strictly anaerobic gram negative bacilli 2. Aerobic bottle turns positive first follow the gram negative aerobic flow chart based on time it turned positive to figure out what bacteria it is <13 hours= Enterobacteriacae 14-20 hours= Pseudomonas >20 hours= Other GNB

What is the microbiology of osteomyelitis?

1. S. aureus (MSSA/MRSA) Most common cause of acute hematogenous osteo Most common isolate in all bone cultures 2. Other pathogens with high occurrence Coag-neg. staphylococi spp, Streptococcus spp., Gram-neg. bacilli

What are the Empiric Tmt Agents in VAP/HAP?

1. Antipseudomonal β-lactams (PICK 1) Piperacillin/tazobactam Cefepime or ceftazidime Meropenem or imipenem/cilastatin Aztreonam 2. Antipseudomonal agents, non β-lactams (PICK 1) Levofloxacin or ciprofloxacin Amikacin, gentamicin or tobramycin (no monotherapy) Colistin or polymyxin B (no monotherapy) 3. Anti-MRSA (PICK 1) Vancomycin Linezolid

What are the Candida UTIs?

1. Asymptomatic Remove urinary catheters Antifungal tmt NOT recommended unless has risk factors 2. Symptomatic Fluconazole 200 mg (3mg/kg) for 2 weeks Alt: AmB deoxycholate or flucytosine, or AmB bladder irrigations

What is the Summary: Role of Cobicistat/PI Combination Therapies?

1. Atazanavir/Cobicistat (Evotaz®) Indication: Tx-naïve and Tx-experienced (and baseline eGFR > 70mL/min when using TDF) Dosing: One tablet daily (300/150mg) with food *Side Effects: Hyperbilirubinemia, ↑ SCr* Resistance Profile: Moderate-genetic barrier Potential for DDIs: Significant DDIs but fewer than RTV boosted PIs [cobicistat-CYP3A4, 2D6 and P-gp inhibitor] Efficacy: Excellent 2. Darunavir/Cobicistat (Prezcobix®) Indication: Tx-naïve and Tx-experienced (and baseline eGFR > 70mL/min when using TDF) Dosing: One tablet daily (800/150mg) with food Side effects: *Sulfonamide(rash), ↑ SCr* Resistance Profile: High genetic barrier Potential for DDIs: Significant DDIs but fewer than RTV boosted PIs [cobicistat-CYP3A4, 2D6 and P-gp inhibitor] Efficacy: Excellent

What are the CABP Organisms?

1. Bacteria- 15% S. pneumoniae, H. influenzae, Atypicals 2. Viruses- 27% Rhinovirus, Influenza 3. No cause identified- 62%

•CF presents 1 week later to the free urgent care clinic you volunteer at on your weekends and is happy to see you, a knowledgeable, familiar pharmacist. •CF states their previous symptoms have continued and they have also developed postnasal drainage and a sore throat. •What is the most likely diagnosis for CF? •What treatment would you recommend for CF? •What monitoring would you recommend?

1. Bacterial rhinosinusitis- persistent 2. Amoxicillin or Augmentin 3. Resolution of symptoms

What is BacterioSTATIC vs BacteriCIDAL?

1. BacterioSTATIC MBC/MIC > 4 < 3 log reduction in CFU(colony forming units)/mL in 18 - 24 hrs 2. BacterioCIDAL MBC/MIC < 4 >3 log reduction (99.9%) in CFU/mL in 18 - 24 hrs

What is a UTI?

1. Bacteriuria ≠ infection (UTI) 2. (+/-) Bacteriuria + SYMPTOMS = infection (UTI) 3. Bacteriuria WITHOUT symptoms = Asymptomatic bacteriuria (ASB)

What are the Common Resistance Mechanisms Gram +?

1. Beta-lactamases 2. Altered penicillin binding proteins 3. Efflux pumps: Expels drug from the bacteria before it can be effective 4. Alterations of target binding sites: Prevent the antibiotic from binding to its site of action

What is Blastomycosis?

1. Blastomyces dermatitis North America Mississippi, Ohio, St. Lawrence River Valleys and Great Lake regions 2. Clinical manifestations PNA, extra-pulmonary 3. Diagnosis: Visualization with fungal stains/culture 4. Treatment: Mild/moderate: itraconazole Severe: AmB then itraconazole CNS: AmB then voriconazole or fluconazole

What is the empiric therapy for Healthcare Associated intra-abdominal infections?

1. Single agent Imipenem/cilastatin, Doripenem Meropenem, Piperacillin/tazobactam IF < 20% resistance to P. aeruginosa, Acinetobacter, ESBL, other MDR GNRESBL + organismP. aeruginosa > 20% resistance to ceftazidime 2. Combination Cefepime or ceftazidime PLUS Metronidazole IF < 20% resistance to P. aeruginosa, Acinetobacter, ESBL, other MDR GNR 3. Combination Single agent PLUS Aminoglycoside IF ESBL + organismP. aeruginosa > 20% resistance to ceftazidime

What are the Empiric Antibiotics for Intra-abdominal infections?

1. Single agents: Ertapenem Meropenem Piperacillin/tazobactam Cefoxitin Moxifloxacin Tigecycline Imipenem/cilastatin Doripenem 2. Combination therapy (all plus metronidazole) Ceftriaxone Cefotaxime Ceftazidime Cefepime Ciprofloxacin Levofloxacin (Gentamicin/tobramycin) + (metronidazole or clindamycin) +/- ampicillin

What is the Major Duke Criteria? Don't need to memorize

1. Blood culture positive for IE 2. Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus, or microorganisms consistent with IE from persistently positive blood cultures defined as follows: at least 2 positive cultures of blood samples drawn >12 h apart or all 3 or a majority of ≥4 separate cultures of blood 3. Single positive blood culture for Coxiella burnetii or anti-phase 1 IgG antibody titer ≥1:800 4. Evidence of endocardial involvement 5. Echocardiogram positive for IE (TEE recommended for patients with prosthetic valves, rated at least possible IE by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients) defined as follows: oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; abscess; or new partial dehiscence of prosthetic valve or new valvular regurgitation (worsening or changing or pre-existing murmur not sufficient)

What are the important labs for diagnosing meningitis?

1. Blood cultures 2. Lumbar puncture - Gram stain and fluid analysis 3. Rapid diagnostics - Lactate and procalcitonin

How is IE diagnosed?

1. Blood cultures 3 sets of cultures obtained from different sites 1 hour between first and last set (IA) 2. Echocardiography Should be performed expeditiously in patients suspected of having IE (IA) 3. Clinical observation

What are the ARV Therapy-Associated Adverse Events That Can Be Managed with Substitution of Alternative ARV Agent?

1. Bone density effects Change from TDF to TAF or ABC 2. Jaundice and Icterus Change from ATV, ATV/r, ATV/c to DRV/c, DRV/r, INSTI, NNRTI 3. Neuropsychiatric side effects Change from EFV, RPV to DOR, ETR, PI/c, PI/r 4. Renal effects Change from TDF to TAF or ABC

A 67 yo male presents to his primary care physician with a 2 day history of cough, purulent sputum and shortness of breath PMH: CAD, DM, allergies: erythromycin Imaging: CXR small focal consolidation in the left lower lobe Vitals: 122/87, HR 85, RR 25, temp 99.7F What type of PNA does this patient have? Provide support with subjective and objective information Recommend appropriate empiric therapy for this patient What type of PNA does this patient have? Provide support with subjective and objective information Recommend appropriate empiric therapy for this patient

1. CABP Organisms: Strep pneumo, atypicals, h. influenzae 2. Augmentin and Azithromycin

1. Which two co-receptors does HIV utilize for entry? 2. Which co-receptor predominates early in HIV infection? 3. Which ARV is a gp41 inhibitor? 4. What is this ARV also referred to as? 5. Enzyme for HIV RNA to HIV DNA. Which two classes work here? 6. Enzyme into genome 7. Enzyme responsible for budding (class too)

1. CCR5 and CXR4 2. CCR5 is predominates early in infection 3. Fuzeon 4. entry inhibitor 5. Reverse transcriptase Classes: NRTIs NNRTIs 6. Integrase, Integrase inhibitors first-line for treatment 7. Protease Inhibitors

What will a culture result look like?

1. Source: blood -Important to know the source. You will treat it differently depending on the source. Think CSF infection vs urine 2. Final result -Final result means that this is the only organism present. Before it is finalized, it will say preliminary meaning that you'll have to check back for the final report 3. Organism: E. coli in ALL bottles -Organism is E. coli in ALL bottles, this is also important 4. INT = Interpretation S= OK to use I = Maybe R = Don't use . For S: it means that you can most likely use this antibiotic. Of course you'll still need to verify that it gets to the site of intended activity and that they patient doesn't have any contraindications prior to using it. Intermediate means that you might be able to use it depending on the MIC value and if the antibiotic concentrates well there. We usually don't use antibiotics that are intermediate unless we have no other choice. R is resistance. Don't use an antibiotic that is resistant.

What are the main Gram positive bacteria?

1. Staph aureus -MSSA (Methicillin sensitive Staph aureus) -MRSA (Methicillin resistant Staph aureus) 2. Enterococci -VRE (Vancomycin resistant Enterococci) 3. Streptococci

What is the empiric therapy for VAP?

1. Staph aureus activity MRSA Risk: ANY of the following: - Risk for antimicrobial resistance - In unit with > 10 - 20% of S. aureus are MRSA Yes, Vancomycin OR Linezolid No, Other agent w/MSSA activity 2. Antipseudomonal activity If ANY of the following: - Risk for antimicrobial resistance - >10% resistance to selected monotherapy - Structural lung dz Yes, combo therapy 2 antipseudomonal agents: Pick 1 Beta-lactam PLUS Pick 1 Non-Beta-lactam No, Monotherapy with EITHER antipseudomonal Beta-lactam OR Non-beta-lactam (NOT aminoglycoside or polymyxin)

What are the gram positive cocci?

1. Staph- clusters S. aureus S. epidermidis 2. Strep- chains S. pneumoniae S. pyogenes(Group A) S. agalactiae(Group B) Viridans streptococci 3. Enterococci- chains E. faecalisE. faecium

What is the pathophysiology of a UTI?

1. Start as periurethral contamination by a uropathogen residing in the gut 2. Then colonization and migration into bladder/kidney (pyelo) 3. Bacterial virulence mechanisms overcome host defense mechanisms 4. Can also bind a urinary catheter or stone to cause a physical obstruction

What are the Summary: Role of INSTI Combination Therapies?

1. Stribild®/ Genvoya® Dosing: One tablet daily Side Effects: Nausea, headache, insomnia, renal considerations *Genvoya: ↓ renal and bone AEs* Resistance Profile: Low-genetic barrier Potential for DDIs: Significant DDIs [cobicistat-CYP3A4, 2D6 and P-gp inhibitor] 2. Triumeq® Dosing: One tablet daily Side Effects: Headache, nausea, insomnia, (HLA-B*57:01 testing required prior to using abacavir) Resistance Profile: High genetic barrier Potential for DDIs: Few DDIs (dolutegravir primary metabolism is UGT1A1-mediated) 3. Biktarvy® Dosing: One tablet daily Side Effects: Diarrhea, nausea and headache Includes TAF: *↓ renal and bone AEs* Resistance Profile: High genetic barrier Potential for DDIs: Few DDIs (bictegravir primary metabolism is CYP3A and UGT1A1)

What are some non-pharm treatments with IE?

1. Surgery 2. Blood cultures should be repeated every 24 to 48 hours until negative Then not needed unless clinical status worsens Persistently positive blood cultures may indicate Subtherapeutic abx concentrations Inadequate source control 3. Clinical improvement should typically occur within the first week of tmt Resolution of fever, chills, malaise, fatigue and appetite 4. Day 1 of tmt is considered after first negative blood culture

What is the treatment approach for osteomyelitis?

1. Surgery Indicated if patient has not responded to specific antimicrobial treatment Or concomitant joint infection suspected Debridement of tissue Resection Reconstruction 2. Antibiotic treatment Targeted therapy based on Gram-stain and culture

What are the Treatment Options for PJI?

1. Surgical strategies Debridement and retention One or two stage exchange Resection arthroplasty Amputation 2. Antimicrobial therapy Systemic antibiotics Local antimicrobials - Impregnated bone cement

ES, a 24 yo F, presents to her PCP c/o blurry vision and "weird spidery floating thingies" x 2 days PMH: HIV diagnosed 1 yr ago (due to thrush), ART initiated several months ago, hx of poor adherence Medications: Truvada 1 PO daily ( 300 mg TDF/ 200 mg FTC), Reyataz (ATV) 300 mg daily, Norvir (RTV) 100 mg daily, Lipitor 20 mg daily Allergies - sulfa drugs, PCN Labs: CD4 = 46, HIV-1 RNA = 550,000, WBC = 2.3, CMV IgG (+), SCr = 0.4, TC = 124, TG = 377, HDL = 32; all other values WNL. Current Weight = 80kg What is the MOST likely OI that is causing this patient's symptoms? Upon visual inspection, there is a lesion located close to the fovea (<1500 microns) Recommend a treatment plan. Be specific with medication (drug, dose, route, frequency and duration) The patient completed a full course of treatment and is recovering well What additional prophylaxis, if any, does she need based on her CD4 count and for how long?

1. CMV Retinitis -blurry vision and "weird spidery floating thingies" x 2 days CD4=46 2. Intravitreal ganciclovir 2 mg in both eyes and systemic valganciclovir 900 mg PO BID Treat both eyes 3. Neutropenia, thrombocytopenia, anemia Caricnogenic, teratogenic potential, impaired fertility

What are the resistant gram negative bacteria?

1. CRE/KPC- carbapenem-resistant (producing) Enterobacteriaceae/ Klebsiella pneumoniae carbapenemase 2. ESBL producers- Extended spectrum beta lactamases

What are the Infections of the Biliary Tract?

1. Cholecystitis Inflammation of the gallbladder 2. Cholangitis Inflammation of the biliary ductal system Ultrasonography is the first imaging technique Anaerobic antibiotics are not indicated unless biliary-enteric anastamosis is present After cholecystectomy, antimicrobial therapy should be discontinued after 24 hrs unless there is evidence of infection outside of the gallbladder wall

What are some misconceptions around bactericidal vs bacteriostatic?

1. Cidal drugs kill, while static drugs inhibit growth Not true as demonstrated in previous example 2. They are not dynamic processes Yes, they are! Cidal vs static can change based on drug concentrations, MIC and organism tested 3. Refers to the ability of an antibiotic to treat infections of different severity Nope, cidal and static drugs can be used in serious infections Consideration should be given to endocarditis and meningitis

What are the Antimicrobial PD parameters to know?

1. Cmax/MIC(Cmax=10-12xMIC) Concentration dependent Fluoroquinolones Amingoglycosides 2. T>MIC (Cmin>4-5xMIC) Non-concentration dependent Beta-lactams 3. AUC/MIC (AUC:MIC) Total drug exposure Vancomycin

What is Coccidioidomycosis?

1. Coccidioides immitis and C. posadasii San Joaquin Valley Fever 15,000 new infections annually AZ and CA Presents like CAP 2. Diagnosed by serology 3. Treatment: Immunocompetent : no tmt Immunosuppressed, pregnant or severe DOC: fluconazole Alt: itraconazole or AmB

What are the pathogens in bacterial meningitis?

1. Community Acquired Streptococcus pneumoniae: Gram + Diplococci Neisseria meningitidis: Gram - Diplococci Listeria monocytogenes: Gram + rods Haemophilus influenzae: Gram - rods or coccobacilli 2. Healthcare Associated/Ventriculitis Staphylococci:S. aureusCoagulase negative staph Gram negative bacilli - Most common GNB: E coli, Enterobacter, Citrobacter, Serratia, Pseudomonas.

What is the general treatment for each OF THE 3 types of intra-abdominal infections?

1. Community Mild/Moderate Enterics, Strep, Anaerobes Single or Combo (inc FQs), More narrow abx 2. Community Severe Enterics (MDR?), Strep, Anaerobes Single or Combo (inc FQs) w/PsA + anaerobes 3. Healthcare associated Resistant GNR, Anaerobes, Enterococcus?, Candida, MRSA? Single or Combo (NO FQs) w/PsA + anaerobes +/- antiMRSA +/- anti fungal

What are the two types of intra-abdominal infections?

1. Complicated Extends beyond the hollow viscus into the peritoneal space Either abscess formation or peritonitis 2. Uncomplicated Involves intramural inflammation of GI tract Progresses to complicated if not adequately treated They are also *Common* second most common cause of death in the ICU

What are the HPV Treatment options: Provider applied?

1. Cryotherapy (Alt: Podophyllin resin 10 - 25% in compounded tincture of benzoin) 2. Trichloroaceticc acid or bichloroacetic acid 80 - 90% (Alt: Intralesional interferon) 3. Surgical removal (Alt: Photodynamicic therapy) 4. Alt: Topical cidofovir

SF, a 46 yo M, arrives at the ER with altered mental status. It was witnessed that SF had a seizure after babbling incoherently. Five days ago, SF ate a delicious, though somewhat cold, gyro at a Greek food stand. PMH: HIV+ x 5 yrs, HAART x 1 yr with poor adherence, GERD. NKDA Medications: Trizivir 1 BID (300 mg ABC, 150 mg 3TC, 300 mg AZT), Prezista (DRV) 600 mg BID, Norvir (RTV) 100 mg BID, rabeprazole 20 mg QD, fenofibrate 145 mg QD; SH: negative x 3 (no alcohol use, no smoking, and no IVDA) PE: HEENT - oral thrush on lower palate; Skin - small papules on chest, neck, and face all others negative Head CT scan with contrast: ring-enhancing lesions. VS: BP 144/88, Temp 39.2°C, HR 72, RR 20, Wt: 72 kg. Labs: CD4 = 83, HIV-1 RNA = 268,373, WBC = 3.2, toxoplasma IgG (+), SCr = 0.9, all other values WNL Answer the following questions with subjective and objective information from the case. What is the MOST likely OI that is causing this patient's symptoms? Recommend a treatment plan. Be specific with medication (drug, dose, route, frequency and duration) What other agents can you use to minimize the hematological toxicities of pyrimethamine? Can you use folic acid? The patient completed a full course of treatment and is recovering well. What additional prophylaxis, if any, does he need based on his CD4 count and for how long?

1. Cryptococcus, candida, Toxoplasmosis Probably toxo but need a brain biopsy to be sure CD4<100 Would probably just treat and see if they respond, brain biopsy is invasive Can get toxo from Eating raw or undercooked shellfish, cat feces 2. Sulfadiazime + pyrimethamine + lecovorin 3. Hematologic - thrombocytopenia, neutropenia, anemia Monitor for resolution YOU CANNOT USE FOLIC ACID- not trying to inhibit dihydrofolate 4. Sulfadiazime + pyrimethamine + lecovorin until CD4>200 for >6 months along with PCP primary prophylaxis

What are the Rifabutin DDIs?

1. DOR- DOR AUC decreases by 50% Increase DOR to 100 mg twice daily 2. EFV- Ribabutin conc decreases by 38% Rifabutin 450-600 mg/day or Ribatuin 600mg TIW if not used with PI 3. ETR- ETR AUC decreases by 38% Do not administer ETR plus PI/r with Rifabutin Use rifabutin 300 mg/day without PI/r 4. NVP- Rifabutin increases, NVP decreases No dose adjustment- use with caution 5. RPV- increase RPV dose to 50 mg/day 6. ATV, ATV/r, DRV/r, LPV/r, TPV/r, PI/c Rifabutin conc increases drastically Use rifabutin 150 mg once daily or 300 mg TIW 7. BIC- DO NOT COADMINISTER (BIC decreases) 8. DTG- no dose adjustment needed (DTG decreases) 9. EVG/c- DO NOT COADMINISTER (EVG decreases, rifabutin drastically increases) 10. RAL- no dose adjustment needed (RAL AUC increases Cmin decreases)

What is the scoring from the Duke Criteria?

1. Definite Pathological criteria Clinical criteria 2 major, 1 major + 3 minor, or 5 minor 2. Possible 1 major + 1 minor, or 3 minor criteria 3. Rejected Firm alternate diagnosis Resolution of IE with ≤ 4 days of antibiotic therapy No pathological evidence Does not meet above criteria

What are other ABX approved for CABP but not in the ISDA guidelines?

1. Delafloxacin (2017) 2. Omadacycline (2018) 3. Lefamulin (2019) Place in therapy?

What are the Newer Antibiotics Approved Since 2014 Guidelines?

1. Delafloxacin (2017) PROCEED 1 and 2 Phase III vs vancomycin + aztreonam for ABSSSI 2. Omadacycline (2018) OASIS I and II Phase III vs linezolid for ABSSSI

How does Source Control happen?

1. Drain infected foci 2. Control ongoing peritoneal contamination - Diversion/resection 3. Percutaneous drainage of abscess - Preferable to surgical drainage

What is the Resistance in Enterobacterales?

1. ESBL extended spectrum beta lactamases Most commonly K. pneumo and E. coli Enzymes that hydrolyze all PCNs, cephalosporins and aztreonam Types of enzymes *TEM, SHV, CTX-M* 2. CRE/KPC carbapenem resistant entero Most commonly in E. coli, K. pneumo and Enterobacter spp Serine enzymes and metallo-carbapenemases Serine enzymes - Group A (SME, GES, IMI, NMC, *KPC*) and class D Oxa enzymes Most common metallo-carbapenemase - *VIM*

What are some Other Candida Infections?

1. Endopthalmitis Based on susceptibility 4 - 6 weeks of treatment CNS infections AmB + flucytosine with fluconazole step down 2. Vulvovaginal infection No one agent is superior to another 3. Oropharyngeal Mild - clotrimazole troches Moderate/severe - fluconazole 4. Esophageal Systemic therapy is ALWAYS required

Where in the skin do the infections occur?

1. Epidermis/dermis Erysipelas, impetigo, folliculitis, furuncles & carbuncles 2. Hypodermis Cellulitis Necrotizing fasciitis 3. Muscle Myositis

What are the AG dosing strategies?

1. Extended interval (using Hartford Nomogram) Large dose, check random level to adjust interval, most common 2. Traditional dosing - Only if patient doesn't meet requirements for Extended Interval dosing, lower dose used more frequently depending on renal function 3. Synergy dosing -Smallest dosing 1 mg/kg every 8 hours with renal adjustments Covered in Pharmacokinetics-- review

Which antibiotics are associated with C diff?

1. FQs 2. Cephalosporins (Gen 1-3) 3. Clindamycin 4. Any beta lactam/beta-lactamase inhibitor

•LA is a 7 yr old, accompanied by her father who presents to the community pharmacy with complaints of sore throat and fever. LA is fussy and says it feels like her throat is "on fire" when she swallows. Her symptoms began yesterday. •Allergies: amoxicillin (throat swelling, difficulty breathing) •Vitals: Temp 101.9F, Ht 4'1", Wt 24 kg •PE: appears tired, grimacing when swallowing, anterior cervical lymph nodes enlarged and tender, tonsils moist, red, with white exudates Point of Care RADT: Positive •What s/sx point toward GAS pharyngitis rather than viral pharyngitis? •What treatment do you recommend for this patient? (supportive care and infection treatment)

1. Fever, white exudates, swollen, cervical lymph nodes enlarges 2. Ibuprofen, acetaminophen, allergic to amoxicillin: Clindamycin or Azithromycin for 10 days

What are the treatments for herpes?

1. First episode Acyclovir 7 - 10 days Valacyclovir 7 - 10 days Famciclovir 7 - 10 days 2. Recurrent, episodic Acyclovir x 5 days Valacyclovir x 3 - 5 days Famciclovir x 3 - 5 days 3. Recurrent, suppressive Acyclovir daily Valacyclovir daily Famciclovir daily

What are the Cephalosporin generations (1st-5th) (PO vs IV)?

1. First: Good for Gram positive activity Cefazolin, cephalexin, cefadroxil 2. Second: Good for Gram negative activity, less gram positive activity, include Cefamycins (Cefoxitin and cefotetan) which have anaerobic activity Cefuroxime, cefoxitin, cefotetan, cefprozil, cefaclor 3. Third: Increased Gram Negative, still have gram positive activity but not as much Staph activity as 1st/2nd gen Ceftriaxone, cefotaxime, ceftazidime, cefdinir, cefpodoxime, cefixime, ceftizoxime 4. Fourth: Has pseudomonas activity and good gram positive activity Cefepime 5. Fifth: Ceftaroline (Added activity against MRSA) and ceftolozane/tazo (Great gram negative activity) Note: Cefadroxil is an approved first generation cephalosporin, but it is rarely used in the US Cefiderocol does not fall into the generation classification

What is the trend for gay/bisexual men with new HIV diagnoses? Among states in the US?

1. Gay/bisexual men Down 7% *Increasing in pacific islander and native american populations* 2. States in the US Blacks/African Americans in the south have the highest number of HIV infections

What is Antiretroviral Resistance testing?

1. Genotypes (VL>500-1000 copies/mL) Sequences patient's virus by blood sample Mutations reported for patient viral strain as compared to wild type (no mutations) Indication: treatment-naïve patients 2. Phenotypes (VL>500-1000 copies/mL) "Grows" patient's virus in cell culture system and determines resistance/susceptibility to ARVs Do not report mutations (HIV sequence) Reserved for treatment-experienced patients with complex resistance patterns 3. Archive genotypes (VL<20 copies/mL) Next-generation sequencing genotypic resistance test analyzes HIV-1 pro-viral DNA (i.e. detects archived resistance mutations)

A 30 yo male who has sex with men (MSM) presents to his primary care physician with painful urination and purulent urethral discharge He received unprotected oral sex from a new sexual partner 3 weeks ago. He went to a STI clinic and had a positive NAAT for Neisseria gonorrhoeae and received ciprofloxacin 500 mg once without any improvement in symptoms What is the most likely cause of this patient's urethritis? What are this patient's risk factors for STIs? What other additional testing should be done?

1. Gonorrhea, chlamydia, mycoplasma, herpes 2. Unprotected, many partners, MSM 3. Should be tested for chlamydia, HIV, syphilis

What are the gram stains of the anaerobes?

1. Gram Negative Bacteroides spp 2. Gram Positive Peptostreptococcus spp Clostridioides spp.

What bacteria are common in intra-abdominal infections?

1. Gram Negative E. coli K. pneumoniae Proteus spp Enterobacter spp 2. Gram Positive Enterococcus spp Streptococcus spp Staphylococcus spp 3. Anaerobes Bacteroides spp

What are the "Normal" Skin Bacteria?

1. Gram-positive Coagulase-negative staphylococci (CoNS) Micrococci Corynebacterium spp Propionibacterium spp 2. Gram-negative Acinetobacter spp 3. Fungi Malassezia spp Candida spp

What are the Organisms HAP/VAP?

1. HAP Staph aureus (16%) - Approx 2/3 MRSA Enteric Gram negative Rods (GNR) (16%) Non-lactose Fermenting GNR - Pseudomonas aeruginosa (13%) - Acinetobacter baumannii (4%) 3. VAP Staph aureus (20 - 30%) - Approx 1/2 MRSA Enteric Gram negative Rods (GNR) (20-40%) Non-lactose Fermenting GNR - Pseudomonas aeruginosa (10-20%) - Acinetobacter baumannii (5-10%)

*What are the CDC Core Elements?*

1. Hospital leadership commitment 2. Accountability 3. Pharmacy Expertise 4. Action 5. Tracking 6. Reporting 7. Education

How can antimicrobial resistance happen within a person?

1. Human error- pt stopped taking the antibiotic 2. The bacteria is intrinsically resistant to the bacteria and will then multiply causing a bigger problem

What patients will go to the ICU?

1. Hypotension requiring vasopressors OR 2. Respiratory ventilation requiring mechanical ventilator OR 3. Patients with severe PNA + clinical judgement

What is the PID Treatment?

1. IV Cefotetan 2 g q 12 hr PLUS doxycycline 100 mg PO or IV q 12 hr Cefoxitin 2 g q 6 hr PLUS doxycycline 100 mg PO or IV q 12 hr Alt: Amp/sulb 3 g q 6 hr PLUS doxycycline 100 mg PO or IV q 12 hr 2. IM/PO Ceftriaxone 250 IM once PLUS doxycycline 100 mg PO q 12 hr x 14 days+/- metronidazole 500 mg q 12 hr x 14 days Cefoxitin 2 g IM once PLUS probenecid 1 gm once PLUS doxycycline 100 mg q 12 hr x 14 days +/- metronidazole 500 mg q 12 hr x 14 days

What are the Goals of Therapy for osteomyelitis?

1. Identify causative organism and used targeted tmt Eradicate infection I&D, debridement 2. Restore Function Resection or reconstruction Rehabilitation 3. Pain Relief

What are the Types of Hypersensitivity Reactions?

1. IgE Immediate Hives, itching, wheezing, hypotension, anaphylaxis, angioedema 2. IgG or IgM <72 hours but can be up to 15 days Autoimmune hemolytic anemia, thrombocytopenia 3. IgG or IgM 1 - 3 weeks Serum sickness, fever, rash, lymphadenopathy, joint pain 4. Multiple Variable (days to weeks) DRESS, SJS, contact dermatitis

What are the HPV Treatment options: Patient applied?

1. Imiquimod 3.75% or 5% cream 2. Podofilox 0.5% solution or gel 3. Sincerechin 15% ointment

What are some tips on culture interpretation?

1. In general, lower MIC is better But... you need to compare each bug drug combination Want to select antibiotic that is farthest away from its breakpoint 2. Select an antibiotic based on patient specific factors Site of infection (antibiotic penetration) Route of administration Allergies Etc

What are the Consequences of Polypharmacy?

1. Increased Costs 2. Increased Pill Burden 3. Increased Adverse Effects 4. Increased Drug-Drug Interactions (DDIs) All of these factors can affect adherence to ART Potential loss of ART efficacy (virological breakthrough) -Increased non-adherence to ART -Possible reduced available future ART options

What are the treatments for C diff?

1. Initial episode non-severe WBC<15,000 and SCr<1.5 - Vancomycin 125 mg QID for 10 days OR - Fidaxomicin 200 mg BID for 10 days - Use metronidazole 500 mg TID if above not available 2. Initial episode severe WBC>15,000 or SCr>1.5 - Vancomycin 125 mg QID for 10 days OR - Fidaxomicin 200 mg BID for 10 days 3. Initial episode fulminant: hypotension, shock, ileus, megacolon - Vancomycin 500 mg QID PO or NG, if ileus add rectal Vanco administration - AND Metronidazole 500 mg IV Q8Hrs, esp. if ileus present 4. First recurrence - Vancomycin 125 mg QID for 10 days if Metronidazole was used for first episode OR - Use prolonged, pulsed, tapered Vanco if standard treatment for first episode OR - Use Fidaxomicin 200 mg BID for 10 days if vanco for first episode 4. Second recurrence - Vanco tapered and pulsed regimen OR - Vancomycin 125 mg QID for 10 days followed by rifaximin 400 mg TID for 20 days OR -Fidaxomicin 200 mg BID for 10 days OR -Fecal microbiota transplant

What are the four types of antimicrobial resistance?

1. Intrinsic Occurs in the genome through gene mutation 2. Acquired Receipt of new genetic material from another organism 3. Plasmids Large segments of genetic material that can be transferred 4. Chromosomal elements Can transfer independently or mobilized by plasmids

What are the Severity Risk Factors for osteomyelitis?

1. Local Factors Major vessel compromise Extensive Scarring Radiation fibrosis Chronic lymphedema Inflammation of arteries 2. Systemic Factors Renal/ liver failure Alcohol/ tobacco abuse Immune deficiency/ immunosuppression Diabetes mellitus Elderly age Malignancy

What are the Common Resistance Mechanisms Gram -?

1. Loss of porins: Reduces the movement of antibiotic through the cell membrane (can't get into the cell) 2. Mutations in lipopeptide structure: Unable for antibiotic to bind its target 3. Plasmid mediated -Beta-lactamases -Increased efflux: Expels drug from the bacteria before it can be effective -Antibiotic modifying enzymes (AME): Makes the antibiotic incapable to interacting with its target -Target mutations -Ribosomal mutations/modifications: Prevent the antibiotic from binding and inhibiting its protein synthesis -Bypass targets: Use an alternate resistant enzyme to bypass the inhibitory effect of the antibiotics

What are the ADEs/monitoring of macrolides?

1. Lots of DDI with CYP P450 enzymes (least is azithromycin) 2. QTc prolongation (worst is erythromycin) 3. GI upset (worst is erythromycin because it acts as motilin receptor agonist in GI tract, can be used for GI motility)

What are the treatments for Complicated Cystitis?

1. Low Risk of MDR Pathogen (<20%) Ceftriaxone 1 gm daily Levofloxacin 750 mg IV daily Cefepime 1 gm q 12h Pip/tazo 3.375 gm IV q 6h Gentamicin 5 mg/kg daily If PCN allergic: Aztreonam 2 gm IV q 8h 2. High Risk of MDR Pathogen (≥20%) Meropenem 500 mg - 1 gm IV q 8h Ceftolozane/tazo 1.5 gm IV q 8h Ceftazidime/avi 2.5 gm IV q 8h Meropenem/vaborbactam 4 gm IV q 8hr

What imaging is done for IE?

1. Low patient risk/clinical suspicion= TTE (trans-thoracic echocardiogram, outside of body) 2. High patient risk/clinical suspicion/difficult imaging patient= TTE initially followed by TEE (trans-esophageal echocardiogram, requires sedation, inside body into esophagus) ASAP

A 45 year-old F with HIV infection who weighs 80 kg and has a CD4 count of 30 cells/mm3 is admitted to the hospital for fevers, night sweats, malaise, severe abdominal cramping, and diarrhea. She is currently not on treatment for HIV. During the hospital stay, mycobacterial cultures of the blood and of a bone marrow aspirate grow Mycobacterium avium complex Answer the following questions with subjective and objective information from the case. What is the MOST likely OI that is causing this patient's symptoms? Recommend a treatment plan. Be specific with medication (drug, dose, route, frequency and duration) The patient is started on treatment and the team wants to start an HIV regimen. The team decides to start bictegravir/tenofovir/emtricitabine (Biktarvy) What recommendations do you have, considering that this patient needs to be on MAC treatment for a least 1 year? What additional prophylaxis, if any, does this patient need based on the CD4 count and for how long?

1. MAC 2. Azithromycin + Ethambutol + Rifabutin B/c patient not on ART= Orange body fluids GI upset, arrhythmias DDIs 3. CMV and PCP, toxo

What is MIC vs MBC?

1. MIC - minimum inhibitory concentration 1st clear tube- you want a lower MIC The lowest concentration of an antimicrobial agent that results in the inhibition of visible growth of an organism 2. MBC - minimum bactericidal concentration After plated blank tubes, it is the 1st clear plate Minimum concentration that prevents growth on a subculture of inhibited serial broth dilutions

What are the resistance GPC?

1. MRSA 2. VRE (E. faecalis or E. faecium)

What are the resistant Gram positives?

1. MRSA 2. VRE (vancomycin-resistant enterococci) Enterococcus faecalis or E. faecium

What is a High risk for MRSA or Pseudomonas in DFI?

1. MRSA (Empiric anti-MRSA recommended) History of previous MRSA or colonization within the last year Local prevalence of MRSA is high so that there is a reasonable probability of MRSA infection Severity of infection is severe enough that not having empiric activity against MRSA would be detrimental 2. Risk for Pseudomonas? High local prevalence of Pseudomonas infection Warm climate Frequent exposure of the foot to water

What is the IE Definitive therapy for a patient with a Staph aureus infection?

1. MRSA native valve: Vancomycin or Daptomycin 2. MRSA prosthetic valve: Vancomycin + Gentamicin + Rifampin 3. MSSA native valve: Beta-lactam (Nafcillin or oxacillin) OR Cefazolin 4. MSSA prosthetic valve: Naf/oxacillin + Gentamicin + Rifampin

What are the Susceptible GPC?

1. MSSA 2. Streptococcus 3. Enterococcus faecalis

What are the *susceptible* gram positive bacterias?

1. MSSA 2. Streptococcus spp 3. Enterococcus faecalis

What are the IV Antibiotic Regimens for osteomyelitis?

1. MSSA Nafcillin 2 gm IV q4h Oxacillin 2 gm IV q4h Cefazolin 2 gm IV q8h 2. MRSA or Coagulase-negative Staphylococcus spp Vancomycin 15-30 mg/kg IV q8-12h, Trough: 15-20 mcg/mL

What are some common CNS infections?

1. Meningitis - Bacterial- Community, Healthcare associated - Viral 2. Ventriculitis 3. Encephalitis 4. Brain/Epidural Abscess

What is the treatment for Trichomoniasis?

1. Metronidazole or tinidazole 2 g PO X 1 2. Metronidazole 500 mg PO BID x 7 days Alt: If regimen fails, susceptibility testing is recommended

What is the DFI treatment?

1. Mild - MSSA or Streptococci give Cephalexin or Amoxicillin - clavulante - MRSA give Doxycycline or Trimethoprim/sulfa 2. Moderate or Severe - MSSA, Streptococci, Enterobacterales, obligate anaerobes give Ampicllin-sulbactam, Ertapenem or Imipenem/cilastatin - MRSA give Vancomycin - Pseudomonas give Piperacillin/tazobactam

What are the classifications for non-purulent cellulitis?

1. Mild Does not fit moderate or severe Treatment: Oral abx 2. Moderate Systemic s/s of infection Poor adherence Treatment: IV beta lactam 3. Severe Failed I&D + oral abx Systemic infection (fever, > HR, > RR, WBC > 12) Immunocompromised Evidence of deeper infection, bullae, skin sloughing, hypotension, organ dysfunction Treatment: Hospitalized, IV abx

What are the classifications of Purulent Cellulitis?

1. Mild S/Sx: Does not fit moderate or severe Treatment: I&D 2. Moderate Systemic s/s of infection Multiple sites of infection Rapid progressive infection Extremes of age, comorbidities, immunosupression Abscesses in difficult to drain areas Lack of response to I&D alone Treatment: Out patient PO abx targeted towards MRSA 3. Severe Failed I&D + oral abx Systemic infection (fever, > HR, > RR, WBC > 12) Immunocompromised Treatment: Hospitalized, IV abx

What are the treatments for non-purulent cellulitis?

1. Mild- PO Penicillin VK or cephalexin or dicloxacillin or clindamycin 2. Moderate- IV Penicillin or Ceftriaxone or Cefazolin or clindamycin 3. Severe Emergent surgical debridement, rule out necrotizing process Empiric: Vanco plus Piperacillin/tazo

How can you evaluate penicillin allergies?

1. Mild/moderate/intolerance= give a cephalosporin 2. Severe allergy= ask if they tried cephalosporin (yes-recommend, no-alternative) 3. Undocumented= try to get history (if they cant, ask family, if family can't use alternative) 4. Unknown- see undocumented

What are the Severity statuses in DFI?

1. Mild: local infection (no deeper tissues, no systemic signs) Local infection involving only the skin and the subcutaneous tissue (without involvement of deeper tissues and without systemic signs). If erythema, must be >0.5 cm to ≤ 2 cm around the ulcer. 2. Moderate: local infection, deeper tissues (no systemic signs) Local infection with erythema > 2 cm, or involving structures deeper than skin and subcutaneous tissues (eg, abscess, osteomyelitis, septic arthritis, fasciitis),and no systemic signs 3. Severe: local infection, deeper tissues, AND systemic signs and symptoms Local infection with systemic signs of infection ( ≥2 of the following: Temp >38°C or <36°C, HR >90 beats/min, RR>20, WBC >12 000 or <4000 cells/uL)

What are the empiric and definitive treatments for purulent cellulitis?

1. Moderate Empiric: Bactrim or doxycycline Definitive: For MRSA: Bactrim For MSSA: Dicloxacillin or cephalexin 2. Severe Empiric: Vanco or Linezolid or Dapto or Televancin or Ceftaroline Defined: MRSA: Use empiric MSSA: Nafcillin or Cefazolin or Clindamycin

What are the Complications of IE?

1. Mortality 2. Embolization - New embolism risk is highest within the first two weeks of antibiotic therapy - 20 - 50% of cases 3. CHF - Distortion or perforation of valvular leaflets - Rupture of chordae tendineae or papillary muscles - Perforation of cardiac chambers 4. Valvular abscesses and pericarditis 5. Heart blocks/arrhythmias

What is the Resistance in Enterococcus?

1. Most common species E. faecium and E. faecalis 2. Glycopeptides Vancomycin MIC > 32 mcg/mL Changes D-ala to D-lac or D-ser 6 phenotypes (VanA and VanB) Plasmid mediated 3. Ampicillin Due to altered PBP

What are the treatments for Epididymitis?

1. Most likely caused by CT and NG Ceftriaxone 250 mg IM once PLUS doxycycline 100 mg q 12 hr for 10 days 2. Most likely caused by CT, NG and enteric (insertive anal sex) Ceftriaxone 250 mg IM once PLUS levofloxacin 500 mg daily for 10 days 3. Most likely caused by enteric Levofloxacin 500 mg daily for 10 days

22 yo female reports to the ED with vaginal "itchiness". She is sexually active with a new partner ROS: mild superpubic discomfort, urinary frequency, but no fever, pain with urinary or CVA tenderness. Otherwise negative review of systems. Vaginal exam: mild tenderness on vaginal walls, slight erythema, mild, thin, foul smelling discharge Wet mount of vaginal secretions is sent and comes back with motile protozoa What is the most likely diagnosis? Recommend empiric treatment for this patient

1. Motile Protozoa= Trich 2. Metronidazole 2 g PO x 1 dose

Which of the HIV drugs have lots of DDIs?

1. NNRTIs: Doravirine- least Etravirine- most Efavirenz- middle Rilpivirine- least 2. Integrase inhibitors: All are UGT substrates Raltegravir- none Dolutegravir- minimal Bictegravir- most 3. Protease inhibitors: Ritonavir- All of the CYPs and UGT 4. PK inhibitors Cobicistat- some

How to use PRECISION MEDICINE to Guide Choices in Antiretroviral Therapy?

1. NRTI: Abacavir (CPIC level A, PharmGKb level 1A) •HLA-B*5701 testing (hypersensitivity reaction) 2. PI: Atazanavir (CPIC level A, PharmGKb level 1A) •UGT1A1 testing (hyperbilirubinemia) 3. NNRTI: Efavirenz (CPIC level A, PharmGKb level 1B) •CYP2B6 testing (CNS adverse effects) 4. INSTI: Dolutegravir (CPIC level B/C) •UGT1A1 testing (CNS adverse effects) •Role remains to be determined?

What are the Primary Adverse Effects of NNRTIs?

1. Nevirapine (NVP) Rash (including SJS), hepatotoxicity 2. *Efavirenz (EFV)* CNS AEs (vivid dreams, drowsiness, exacerbation of depression), rash, false+ cannabinoid and BDZ tests, and QT prolongation *take on an EMPTY stomach* 3. *Rilpivirine (RPV)* CNS AEs, QT interval prolongation, rash, hepatotoxicity, depression, insomnia *take with food* 4. Etravirine (ETR) Fewer CNS AEs versus efavirenz, rash, nausea *take with food, higher genetic barrier to resistance* 5. *Doravirine (DOR)* Fewer CNS AEs versus efavirenz, nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, and abnormal dreams *higher genetic barrier to resistance, no food restrictions*

What is the Inpatient Empiric Therapy for CAP?

1. Non-severe Beta-lactam + macrolide OR Respiratory FQ 2. Severe Beta-lactam + macrolide OR Beta-lactam + respiratory FQ Macrolide should be azithromycin 500 mg daily or clarithromycin 500 mg twice daily

How is Syphilis diagnosed?

1. Non-treponemal test VDRL - general disease research laboratory RPR - rapid plasma reagin 2. Darkfield examinations Detect from exudate or tissues

What do the CNS Fluid Findings tell you about the type of meningitis? Don't need to memorize, just general idea

1. Normal WBC (cells/mm#) < 5 (<30 in newborns) Differential: Monocytes Protein (mg/dL): < 50 Glucose (mg/dL): 45 - 80 CSF/blood glucose ratio: 50 - 60% 2. Bacterial WBC (cells/mm#) 1000 - 5000 Differential: Neutrophils Protein (mg/dL): Elevated Glucose (mg/dL): Low CSF/blood glucose ratio: Decreased 3. Viral WBC (cells/mm#) 5 - 500 Differential: Lymphocytes Protein (mg/dL): Mild elevation Glucose (mg/dL): Normal CSF/blood glucose ratio: Normal 4. Fungal WBC (cells/mm#) 100 - 400 Differential: Lymphocytes Protein (mg/dL): Elevation Glucose (mg/dL): Low CSF/blood glucose ratio: Decreased

What are the ASP Goals?

1. Optimize clinical outcomes Individualized antimicrobial therapy 2. Minimize unintended consequences Antimicrobial toxicity Selection of pathogenic organisms Emergence of resistant pathogens

What are the Beta-lactams for CABP?

1. Outpatient Amoxicillin 1 g 3 times daily Amoxicillin-clavulanate 500 mg/125 mg three times daily 875 mg/125 mg twice daily 2 g / 125 mg twice daily Cefpodoxime 200 mg twice daily or cefuroxime 500 mg 2 times daily 2. Inpatient Ampicillin/sulbactam 1.5 - 3 gm IV every 6 hrs Cefotaxime 1 - 2 gm IV every 8 hrs Ceftriaxone 1 - 2 gm IV every day Ceftaroline 600 mg IV every 12 hrs Why is a beta-lactam (most often) combined with another agent?

What are the goals of treatment of IE?

1. Overall Goals Eradicate causative organism Reduce associated Morbidity (cardiac and embolic) and Mortality 2. Patient/Treatment Goals Resolution of clinical signs and symptoms Reduce/avoid toxicities and other adverse events Reduce readmission Increase compliance/treatment success

35 yo F presents with c/o cough, fever, HA, and SOB. A HIV test is performed and the results are positive. PMH: HTN. Medications: Yaz, lisinopril-HCTZ 20-25 mg; NKDA. PE: HEENT - thrush on upper and lower palate; Lungs - rales at bases; CXR: bilateral patchy infiltrates, ground glass appearance VS: BP 135/85, Temp 40.5°C, HR 85, RR 25, Wt: 50 kg, pO2 62mmHg Labs: CD4 = 121, HIV-1 RNA = 675,000, WBC = 6.6, AFB (-), SCr = 0.6; all other values within normal limits (WNL) Disposition: patient will be admitted to the ICU Answer the following questions with subjective and objective information from the case. What is the MOST likely OI that is causing this patient's symptoms? Recommend a treatment plan. Be specific with medication (drug, dose, route, frequency and duration) The patient completed a course of treatment and started on ART. What additional prophylaxis, if any, does she need based on her CD4 count and for how long?

1. PCP due to ground glass x-ray Severe due to oxygenation status pO2<70 2. TMP/SMX 250 mg IV Q6 hours x 21 days, change to PO when possible PLUS prednisone Monitor for rash, Fever Leukopenia, thrombocytopenia, Azotemia, Hepatitis, Hyperkalemia 3. Prophylaxis= Secondary prophylaxis Bactrim DS 1 QD until CD4 counts above 200 for 3 months

What is allergy Education?

1. Patient Target high risk groups 2. Provider 3. Prevention of re-labeling Occurs frequently

14 yo female arrived to the ED with her mother complaining of 6 day history of lower abdominal pain associated with dysuria and mild fever PE: tender abdomen in the LRQ with mild guarding and rebound tenderness Social hx: sexually active with her boyfriend and not using any form of contraception Labs: WBC 13.6, CRP 5.4, ESR 47, HCG negative Imaging: abdominal US showed normal appendix and ovaries with small free pelvic fluid. Transvaginal US showed thicken, fluid filled fallopian tubes GYN exam: cervical and uterine motion tenderness and vaginal discharge What is the most likely diagnosis? Recommend empiric treatment for this patient Other issues related to patient age?

1. Pelvic Inflammatory Disease (PID) 2. Ceftriaxone 250 IM once PLUS doxycycline 100 mg PO q 12 hr x 14 days (+/- metronidazole 500 mg q 12 hr x 14 days) 3. Vaccinations? HPV, counsel on safe sexual practices

What is the Resistance in Staphylococcus?

1. Penicillin Inducible beta-lactamase (penicillinase) 2. Methicillin MRSA produces PBP2a, encoded by the mecA gene 3. Lincosamides erm genes 4. Glycopeptides Transfer of vanA cluster from VRE hVISA (heterogenous vancomycin intermediate Staph aureus) and VISA (vancomycin intermediate Staph aureus)

What is the Resistance in S. pneumo?

1. Penicillin resistance Altered PBP (PBP1A, PBP2X, PBP2B) *no benefit from adding beta lactamase inhibitor* Intrinsic or acquire 2. Macrolides and lincosamides erm gene Efflux pump MLSB 3. Fluoroquinolones Inhibition of DNA topoisomerase II and IV Levofloxacin resistance is uncommon (requires a 2-step vs a one step rotation)

What is the IE Definitive Therapy for a patient with an Enterococcus infection?

1. Penicillin susceptible Gentamicin susceptible with a native or a prosthetic valve: 3 options - 1.Ampicillin + gentamicin - 2.Ampicillin + ceftriaxone - 3.Vancomycin + gentamicin 2. Penicillin resistant Aminoglycoside resistant Vancomycin resistant with a native or prosthetic valve: 2 options - 1. Daptomycin - 2. Linezolid

What are the beta lactams?

1. Penicillins - Natural - Anti-staphylococcal - Amino - Combinations 2. Cephalosporins - IV, PO 3. Carbapenems - Combinations -*Imipenem was first but deactivated dehydropeptidase I (DHP-I) in the kidneys brush border, combined with cilastatin so it is not degraded* -Other carbapenems dont have this issue 4. Monobactams

How is the percentage of patients at each stage of the HIV testing and treatment?

1. People living with HIV 2. People living with HIV and know their status 60% 3. People living with HIV and using ART therapy 46% 4. People living with HIV and are virally suppressed 38%

What is the treatment for Pediculosis Pubis?

1. Permethrin 1% cream rinse, apply to affected area, wash off after 10 min Alt: Malathion 05% lotion applied 8 - 12 hr then washed off 2. Pyrethrins with piperonyl butoxide, apply to affected area, wash off after 10 min Alt: Ivermectin 250 mcg/kg PO, repeated in 2 weeks

What is the treatment for Scabies?

1. Permethrin 5% cream 2. Ivermectin 200 mcg/kg PO once, repeat in 2 weeks Alt for both: Lindane 1%, 1 oz location or 30 g creamApply thinly to all areas of the body from the neck down, wash off after 8 hours

What about PI and INSTI MONOTHERAPY?

"Protease inhibitor (PI) monotherapy is inferior to combination antiretroviral therapy (ART).2-6 Integrase strand transfer inhibitor (INSTI) monotherapy has resulted in virologic rebound and INSTI resistance (AI)".

What did sir Alexander Fleming say about antimicrobial resistance?

"The microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out...In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted." ~ Sir Alexander Fleming

What are the Current Strategies for Allergy Delabeling?

*Allergy reconciliation* *Penicillin skin testing* *Education (patient, family, provider)* Graded challenges Review of prior exposure Allergy pathways EMR/order set modification

What are the ADEs/monitoring for metronidazole?

*BBW - carcinogenic in mice and rats therefore should only be used in approved conditions* Disulfiram reaction with alcohol GI effects - N/V/D, metallic taste Peripheral neuropathy Increased INR and prothrombin

What are the ADEs/monitoring for TCNs?

*BBW for tigecycline = increased mortality, should only be used if no alternative (salvage therapy)* - DO NOT use in bacteremia due to large Vd (volume of distribution) which means low serum levels so they should not be used for bacteremia - GI effects: Doxycycline pill esophagitis for PO forms, due to mid-esophageal ulceration because it can cause high acidity or might lodge in esophagus. Take with plenty of water, standing, well before bedtime - severe nausea and vomiting up to 50% for tigecycline - Photosensitivity, especially Doxycycline due to UV-B light - Discoloration of developing teeth (CI in pregnant women and children < 8 years old), deposited in calcifying areas of the bone and will appear yellow or gray PERMANENTLY, you can only cap with porcelain to get rid of it, in children this can cause inhibition of bone growth - Oral forms chelate cations resulting in reduced bioavailability: interactions with foods and antacids Ca, Mg, Fe, Al interfere with absorption of tetracyclines

What are the HACEK Organisms? Don't need to memorize

*Frequently associated w/culture negative IE* because they take a long time to grow *Fastidious Gram - negative bacilli* - Haemophilus spp - Aggregatibacter spp - Cardiobacterium hominis - Eikenella corrodens - Kingella kingae Ceftriaxone is reasonable treatment for HACEK organisms

What are the Goals of Treatment with ARV Therapy?

*Maximally and durably suppress viral load (achieved with adherence to ART)* Reduce HIV-related morbidity and prolong the duration and quality of survival Restore and preserve immunologic function Prevent HIV transmission

What are the risk factors for prosthetic joint infections? (7)

*Obesity* Immunocompromised status Inflammatory arthritis Renal disease Mental health disorders Tobacco use Diabetes

What are the Carbapenem toxicities?

*Seizures* Dori/erta < meropenem < imipenem - Think imipenem and seizures (more likely if dosed in excess of renal function) - GABA normally binds to receptor, channel opens and signal is able to flow - With Imipenem, binds better to GABA-A which closes the channel, renally cleared so this usually only happens with high doses with renal impairment

TAF versus TDF- What's the difference?

*TAF cleaner on kidney and bone* TAF is hydrolyzed within cells by Cathepsin A to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate. P-gp substrate 91% lower plasma TFV levels minimize renal and bone effects while maintaining high potency for suppressing HIV Renal parameters improved in patients who switched to FTC/TAF, with an increase in eGFR and a reduction in proteinuria, *especially in the excretion of b2-microglobulin and retinol-binding protein, which are considered specific markers of proximal tubulopathy.* 15 BMD also improved in patients who switched, and changes were significantly greater in the FTC/TAF group at 96 weeks, with a greater likelihood of improvement in clinical bone density status (osteoporosis, osteopenia, or normal).

What are the AG ADEs/monitoring?

*Toxicity: BBW for nephrotoxicity, ototoxicity and neurotoxicity* Monitoring: 1. Peaks (traditional dosing) for *efficacy* Goal variable, dependent on infection type and MIC 2. Troughs (traditional dosing and synergy dosing) Usually < 1 mcg/mL for *safety, increased troughs increases risk for nephrotoxicity, want this to be low for kidney safety* 3. Random levels (extended interval dosing) Used to determine interval using Hartford Nomogram 4. Renal function

What is the BBW for FQs?

*Toxicity: BBW= tendinitis and tendon rupture, irreversible peripheral neuropathy, and CNS effects* CNS effects include- disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium. Potential risk of coma with hypoglycemia *BBW= Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis, exacerbates symptoms, worst case scenario is not being able to breathe* Fluoroquinolones should not be used in patients at increased risk unless there are no other treatment options available. People at increased risk include those with a history of blockages or aneurysms (abnormal bulges) of the aorta or other blood vessels, high blood pressure, certain genetic disorders that involve blood vessel changes, and the elderly

What are the Integrase Strand Transfer Inhibitors (INSTIs) DDIs?

*Very few DDIs with RALTEGRAVIR and DOLUTEGRAVIR because of minimal CYP450 involvement (i.e. primary metabolism is UGT1A1 glucuronidation)*

What are the Penicillin (PCN) combinations?

- A PCN combined with a beta-lactamase inhibitor - Agents: amoxicillin/clavulanate (PO), ampicillin/sulbactam (IV), piperacillin/tazobactam (IV) - All have anaerobic activity therefore are good for polymicrobial infections that include anaerobes - Piperacillin/tazobactam has activity against Pseudomonas aeruginosa *By adding beta lactamase inhibitor you are only increasing activity for organisms that produce beta lactamase, it doesn't make sense to use a combo for bugs that don't produce beta lactamase* -Example strep pneumo which alters PBPs you wouldn't want to use a PCN combo. Adding like clavulanate just increases GI effects

How would a vancomycin MIC to Staph aureus of 2 mcg/mL impact dosing compared to vancomycin MIC of 1 mcg/mL?

- A higher MIC would mean you would need a greater concentration to be therapeutic - You will have to either increase the dose (can cause toxicity) or increase the interval so the MIC stays above 2 for longer - You can increase time over the MIC with divided dosing as long as you are over the MIC

What are the therapeutic uses for Carbapenems + Combos?

- Agents: imipenem/cilastatin, meropenem, doripenem, ertapenem - Agents combinations:With a beta lactamase inhibitor imipenem/cilastatin/relebactam, meropenem/vaborbactam - All active against anaerobes, Gram negatives, Pseudomonas aeruginosa (*not ertapenem- lacks activity against PEA- Psuedomonas, Enterococci, Acinetobacter*), Acinetobacter (dori - most reliable) > ESBL producing organisms > Polymicrobial infections with aerobes/anaerobes

What are the anti-staph penicillins (PCNs)?

- Agents: nafcillin (IV) and oxacillin (IV) (these 2 are interchangeable) and dicloxacillin (PO) - Drugs of choice for infections caused by MSSA - MSSA = methicillin susceptible Staph aureus - Also have Streptococci activity - Penicillinases started appearing causing Staph resistance. They are beta-lactamases that are able to degrade penicillin, these were produced to overcome that -Methicillin first but not used due to toxicities *You know its MRSA vs MSSA by looking at oxacillin susceptibility (MSSA) vs resistance (MRSA)* MSSA= you can use any beta lactam that has Staph aureus activity

What is the MOA of beta lactams?

- All beta-lactams have essentially the same MOA Bind to penicillin binding proteins (PBPs) ultimately resulting in cell death - The PBPs are proteins which normally play essential roles in a variety of physiologic functions in the bacterial cell, such as maintenance of structural integrity, shape, and cell division - Beta lactams vary in their affinities for the PBPs

What are the ADEs/monitoring for TMP/SMX?

- Dermatologic: Rash, SJS (Steven Johnsons Syndrome) Hematological: bone marrow suppression at higher doses for PCP - Renal impairment- acute interstitial nephritis which can cause acute renal failure, prevents secretion of Cr which elevates SCr without damaging kidneys. Therefore, Increased SCr does not always mean kidney damage - Trimethoprim: Hyperkalemia because structurally similar to triamterene (potassium sparing diuretic) - Trimethoprim: Increased INR with warfarin therapy

What is AG monotherapy used for?

- Monotherapy only for urinary tract infections - Hilf study showed increased mortality in patients with monotherapy for Pseudomonas aeruginosa bacteremia - Newer data suggests that there is no significant difference between functional aminoglycoside therapy (when its in combo but its resistant to the other antibiotic so its basically monotherapy) and inappropriate therapy

What is the ADEs/monitoring for Oxazolidinones?

- Myelosupression -most commonly thrombocytopenia (14 days after started), dosed and time dependent, reversible once DC - Neurotoxicity (with long-term, can resolve but sometimes permanent) - peripheral and optic (loss of color perception or vision, optic resolves more than peripheral) - Weak reversible nonselective MAO inhibitor: DDI with serotonergic agents due to inhibition of monoamine oxidase = potential serotonin syndrome

What are the ADEs/monitoring for FQs?

- PO forms are affected by food and multivalent cations (Mg, Al, Ca) which decreases bioavailability - INR prolongation in warfarin patients - C. difficile infection (CDI) - Lowering of seizure threshold - associated with arthropathiated juvenile animals and juvenile musculoskeletal events in children (reluctance to use in children) Monitoring: 1. Renal function - except for moxifloxacin 2. QTc interval prolongation- more common with moxifloxacin and levofloxacin, cipro the least

What are Additional Pertinent Laboratory Monitoring Parameters?

-CBC with differential, basic chemistry panel, liver panel (AST/ALT/Tbili) at baseline and then every 6 months -Random or fasting lipid profile (triglyceride, cholesterol, LDL, HDL) at baseline and then every 12 months -Random or fasting glucose at baseline and then every 12 months -Urinalysis at baseline and then every 6 months (if using TDF) and every 12 months (if using TAF) -Pregnancy test if clinically indicated (and people of childbearing potential)

What are the Considerations for Evaluating Potential DDIs in Patients Living with HIV?

-Pts who have multiple providers (simplify and Med Rec) -Prescription of new medications and of at least 2 interactive medications -*Co-administration with herbals/OTC medications* -Drug-food and drug-disease interactions -*Switching ART (changing ART classes)* -Discontinuation of ART possessing high interactive potential (i.e. inducers and inhibitors) -Knowledge of DDIs can help identify preventable AEs and curb the use of inappropriate medication use -Avoidance of DDIs + proper management of DDIs can save $$$, optimize + improve overall quality of life for HIV pts

What is the pathophysiology of Acute Otitis Media?

1) Inflammation and swelling occur in the Eustachian tube •Viral upper respiratory infection precedes AOM in 70% of cases 2) Fluid becomes trapped in middle ear 3) Bacteria that colonize the nasopharynx enter the middle ear and are not cleared properly 4) Bacteria proliferate and cause infection Children have more laterally, less sloped nasopharynx

What are the Primary Adverse Effects of PIs?

1. *Atazanavir (ATV)* Hyperbilirubinemia, most CVD friendly PI, nephrolithiasis, renal insufficiency, fat maldistribution, skin rash *taking with food improves absorption* 2. *Darunavir (DRV)* Rash (sulfonamide), hepatotoxicity, N/V, diarrhea *taking with food improves absorption, very high genetic barrier to resistance* 3. Tipranavir (TPV) Rash (sulfonamide), cases of fatal/nonfatal intracranial hemorrhage, hepatotoxicity *high pill burden, increased drug-drug interactions (DDIs), very high genetic barrier to resistance* 4. Lopinavir/ ritonavir (LPV/r) GI intolerance (diarrhea), QT prolongation, fat maldistribution 5. Fosamprenavir (f-APV) Rash (sulfonamide), headache 6. Saquinavir (SQV) GI intolerance, QT prolongation (recommended ECG before initiation) 7. Nelfinavir (NFV) Diarrhea 8. Indinavir (IDV) Hyperbilirubinemia, nephrolithiasis *structural similarity to ATV accounts for similar AEs* 9. *Ritonavir (RTV)* GI intolerance, hypertriglyceridemia, taste perversion, paresthesia *RTV is used as a PK enhancer to ↑ concentrations of co-administered PI, dose related DDIs and AEs*

How is acute and chronic Prostatitis treated?

1. Acute Follow with PO FQ for 2 - 4 weeks Ceftriaxone 1 - 2 gm IV q 24 hr Ciprofloxacin 400 mg IV q 12 hr Levofloxacin 500 mg IV q 24 hr 2. Chronic Ciprofloxacin 500 mg PO BID 4 - 6 wks Levofloxacin 500 mg q day 4 - 6 wks Trimethoprim 100 mg PO BID 4 - 12 wks

What is the clinical presentation of osteomyelitis?

1. Acute Osteo Gradual onset of symptoms Local: dull pain, inflammation, tenderness Systemic: fever, rigors 2. Chronic Osteo Presents with local pain and inflammation Deep ulcers that overlie a bony base that fail to heal after weeks of treatment Diabetes patients

1. has better renal/bone outcomes versus TDF 2. The _____________ test is required before considering abacavir use. Why is this pharmacogenomics test important? 3. Which one of the following NRTIs is associated with more favorable lipid effects? TAF/TDF 4. Which NNRTIs are associated with more prominent CNS adverse effects? ___________ 5. True: False for the following statement: CYP2B6 preemptive genotyping may be useful to determine whether patients are at higher risk for CNS adverse effects when treated with efavirenz. 6. Class adverse effects of NRTIs include _______________________ and hepatic steatosis 7. Class adverse effects of NNRTIs include ___________ and elevated LFTs 8. _________________ is associated with scleral icterus/hyperbilirubinemia. 9. __________ genetic testing may help to predict which patients might be at higher risk for this adverse effect when treated with this antiretroviral. 10. Rash is common adverse effect with darunavir, fosamprenavir and tipranavir due to what chemical moiety___________________ 11. True:False for the following statement: Alopecia has been reported recently among African American females using TAF in a series of case reports 12. The following adverse effect_____________ associated with INSTIs might warrant caution in patients with underlying metabolic syndrome 13. True:False for the following statement: Long-acting dual ART including cabotegravir/rilpivirine is expecting FDA approval soon

1. TAF 2. HLA-B 57:01, Hypersensitivity reactions 3. TDF 4. efavirenz, RILPIVIRINE 5. True 6. Lactic acidosis 7. rash 8. atazanavir 9. UGT1A1 10. sulfonamide 11. True 12. weight gain 13. True

What are the Common Arv regimen Combinations?

1. Treatment-Naïve HIV Patients •2 NRTIs + NNRTI •2 NRTIs + boosted PI •2 NRTIs + INSTI 2. Treatment-Experienced HIV Patients •Many factors need to be evaluated in order to create an active and effective ART regimen •Addressed in future slides and case examples in-class

What are the classifications of ABSSSIs?

1. Uncomplicated Folliculitis Furuncles/Carbuncles Cutaneous Abscess Erysipelas Impetigo Cellulitis 2. Complicated Diabetic Foot Infections Pressure Sores Bite Wounds Burns Cellulitis Necrotizing fasciitis 3. Primary Erysipelas Impetigo Cellulitis Necrotizing fasciitis 4. Secondary Diabetic Foot Infections Pressure Sores Bite Wounds

What are the Typical Pathogens in a UTI?

1. Uncomplicated •Escherichia coli •Proteus mirabilis •Klebsiella pneumoniae •Staphylococcus saprophyticus 2. Complicated •Same as uncomplicated PLUS •Pseudomonas aeruginosa •Acinetobacter baumannii •Staphylococcus spp 3. CA-UTI •Short term - mono microbial •Long term - poly microbial •Same as uncomplicated PLUS •Providencia stuartii •Corynebacterium urealyticum •Morganella morganii

A 27 yo male is admitted to the ICU after a multi-vehicle car accident. He suffered multiple injuries and is now intubated and sedated in the ICU. He is currently requiring vasopressors for blood pressure support. He has no medical history and no known drug allergies. After 72 hrs of intubation, he is suspected to have VAP. The hospital's antibiogram shows the following: What type of PNA does this patient have? Provide support with subjective and objective information What risk factors does this patient have for resistant organisms? How does this impact empiric therapy? Recommend appropriate empiric therapy for this patient What type of PNA does this patient have? Provide support with subjective and objective information What risk factors does this patient have for resistant organisms? How does this impact empiric therapy? Recommend appropriate empiric therapy for this patient

1. VAP 2. Intubated= pseudomonas Empiric: Vanco+ cefepime+ amikacin

28 yo African American female presents to her initial prenatal visit at 16 weeks. Since this is her first visit, she has all of her baseline labs done. No PMH Allergies - penicillin = rash Of note, her VDRL was positive, RPR 1:256 Had a history of a fever erythematosus maculopapular rash on trunk, limbs, palms and soles of feet 15 months ago VDLR positive, RPR 1:256 What is the most likely diagnosis? Recommend empiric therapy for this patient

1. VDRL positive= syphilis, latent > 1 year fever erythematosus maculopapular rash on trunk, limbs, palms and soles of feet 15 months ago 2. Benzathine PCN G 2.4 million units IM q wk x 3 doses Alt: NO ALT BECAUSE SHES PREGNANT, MUST HAVE PCN because doxy is contraindicated in prengnacy Desensitize if necessary T. pallidum is the only drug with no resistance to PCN :)

•CF is a 13-year-old, accompanied by their grandmother to the pharmacy counter. CF has sinus pressure/pain, nasal congestion and headache that started 4 days ago. •PMH: allergic rhinitis •Medications: fluticasone nasal spray 50 mcg, 2 sprays in each nostril Qday •NKA •What is the most likely diagnosis for CF? •What treatment would you recommend for CF?

1. Viral rhinosinusitis 2. Analgesics, saline nasal rinse

What is the Rationale for Switching from 3-drug regimen to 2-drug regimen?

1. Within-class switch: •Better safety profile •Reduced dosing frequency •Decreased drug-drug interactions •Higher genetic barrier to resistance •Lower pill burden •Does not require PK boosting •Cost considerations 2. Between class switch: •Maintain viral suppression if there is no resistance to other components of the regimen *NONE of the two-drug regimens have adequate anti-HBV activity and are not recommended in patients with HBV coinfection*

Case #2: JR is a 28-year old male, newly diagnosed with HIV and presents to the clinic to discuss treatment options for his HIV. Regarding treatment, he prefers once daily dosing if possible since he has a hard time remembering taking any medications twice a day. He has a history of depression for which he takes sertraline 50 mg once daily. He has never missed a dose and is well controlled regarding his depression. Baseline resistance testing shows only K103N mutation and he is HLA-B*5701 positive. JR's most recent HIV viral load is 105,000 copies/mL and CD4 cell count is 500 cells/mm3. All other baseline labs are WNL including recent HBV serology testing noted to be negative. 1) Is JR a candidate for starting ARV therapy based on current treatment guidelines? Why or why not? 2) Are there any adherence barriers that need to be addressed or resolved for JR prior to initiating ARV therapy? 3) If you think this patient should be initiated on antiretroviral therapy, which one of the following regimens would you consider? Select all that apply. A. Triumeq® (abacavir/lamivudine/dolutegravir) 1 tab once daily B. Odefsey® (TAF/emtricitabine/rilpivirine) 1 tab once daily w/ food C. Biktarvy® (TAF/emtricitabine/bictegravir) 1 tab once daily D. SymfiLo® (TDF/lamivudine/efavirenz) 1 tablet QHS on an empty stomach E. Dovato® (lamivudine/dolutegravir) 1 tab once daily

1. Yes because he has HIV regardless of CD4 count/viral load 2. Adherence barriers= once daily dose 3. C. Biktarvy® (TAF/emtricitabine/bictegravir) 1 tab once daily E. Dovato® (lamivudine/dolutegravir) 1 tab once daily No abacavir because HLA-B K103N=CANNOT USE EFAVIRENZ efavirenz, RILPIVIRINE= CNS adverse effects *Rilpivirine cannot use RNA>100,000*

What are the Primary Adverse Effects of NRTIs?

1. Zidovudine (AZT) Fatigue, macrocytic anemia, myopathy, hyperlipidemia 2. Lamivudine (3TC) Well tolerated 3. Emtricitabine (FTC) Well tolerated, nail pigmentation 4. Tenofovir disoproxil fumarate (TDF) *Decrease in BMD, renal insufficiency, GI effects* 5. Tenofovir alafenamide (TAF) *Decrease in BMD (less than TDF),* *renal insufficiency (less than TDF),* *greater effect on lipids vs TDF* 6. Abacavir (ABC) Hypersensitivity reaction (*rule out with HLA-B*57:01 testing*), respiratory symptoms, rash, N/V *Only NRTI that doesn't require dosage adjustment in renal failure* 7. Didanosine (ddI) Pancreatitis, peripheral neuropathy, non-cirrhotic portal HTN 8. Stavudine (d4T) Peripheral neuropathy, pancreatitis, hypertriglyceridemia

What is the Initial Antibiotic Selection for rhinosinusitis?

1. first line preferred- Amoxicillin or Amoxicillin/clavulanate 2. Risk factors for pneumococcal species resistance+ amoxicillin/clavulanate 3. amoxicillin allergy (non-severe)- doxycycline cefixime or cefpodoxime +/- clindamycin 4. amoxicillin allergy (severe) doxycycline Duration of Therapy: 5-7 days

What is the Initial Antibiotic Selection for pharyngitis?

1. first line preferred- Amoxicillin* or penicillin 2. penicillin allergy (non-severe) cephalexin, cefadroxil, cefuroxime 3. penicillin allergy (severe) clindamycin, azithromycin Duration of Therapy: 10 days

What is the empiric therapy for AOM?

1. first line preferred- amoxicillin high dose* 2. received amoxicillin within 30 days amoxicillin/clavulanate high dose* 3. amoxicillin allergy (non-severe) cefdinir, cefuroxime, cefpodoxime, ceftriaxone (IM) 4. amoxicillin allergy (severe) azithromycin, clarithromycin, clindamycin

Approximate total population of people with HIV infection in the US is

1.2 million

How is definitive therapy dosed for healthcare associated ventriculitis and meningitis?

10-20x MIC of organism. Based off of CSF concentrations size, output of drain, size of ventricle Can be put directly into the shunt, could be used for pts who don't respond to systemic therapy *Need to be preservative free because it's going directly into CSF* Penicillins and Cephalosporins cannot be given via this route because associated with significant neurotoxicity like seizures

What is a Vancomycin Taper Example?

125 mg PO QID x 10 - 14 days, then 125 mg PO BID x 7 days, then 125 mg PO daily x 7 days, then 125 mg PO q 2 - 3 days for 2 - 8 weeks No evidence to support a metronidazole taper Allows restoration of GI flora

In-class Case 2: You are asked for treatment duration for non-gonococcal septic arthritis in an adult What is the usual duration of antibiotic therapy? Were you able to find the answer? If so, where, specifically in the Sanford Guide? What is the answer?

14-28 days (2-4 weeks) Page 77

What is the Tuskegee Syphilis Study?

1932 - 1972 Track untreated syphilis in Macon County, AL of 399 poor black sharecroppers Not told they had syphilis Suffered from advanced disease and associated complications

What is the BI/NAP1/027 Strain?

2002-2006 unusually severe and recurrent CDI were noted in Canada Associated with fluoroquinolone and cephalosporin use More virulent than other C. difficile strains Binary toxin producing More severe disease

What age group has the highest number of new infections?

25-34 year olds Male to male sexual contact especially in african americans

What are the Crypto Treatment Options?

3 stages of treatment 1. Induction: 2 weeks Preferred: liposomal amphotericin B + flucytosine for 2 weeks Alternative: amphotericin B deoxycholate + flucytosine, amphotericin B lipid complex + flucytosine, fluconazole + flucytosine 2. Consolidation: 8 weeks Preferred: fluconazole 400 mg IV/PO daily for 8 weeks Alternative: Itraconazole 3. Maintenance: 1 year Preferred: fluconazole 200 mg PO daily for 1 year Alternative: none

What is the trend of HIV deaths globally through time?

38 million people globally with HIV *HIV related deaths have fallen* with increased accessibility to ARVs worldwide Although, expecting an incline in mortality for 2020-2021 due to COVID (funds being reallocated, won't have access to medications, or services)

What are the Voriconazole Dosing Strategies?

6 mg/kg q 12 hr for 2 doses then 4 mg/kg q 12 hr Drug-drug interactions CYP2C19 CYP2C19 polymorphisms impact CL Non-linear kinetics

What is the Duration of Therapy for HAP/VAP?

7 days of therapy based on Rate of clinical improvement Radiological improvement Laboratory parameters Recommended to use PCT (procalcitonin) with clinical criteria rather than clinical criteria alone

Which of the following bacteria are common in community acquired bacterial meningitis? A Streptococcus pneumoniae B Enterobacter C Staphylococcus aureus D Pseudomonas aeruginosa

A Streptococcus pneumoniae

How can antimicrobial resistance happen within an instiution?

A patient is infected with a resistant pathogen and is transferred to the hospital from another facility MDRO= multi-drug resistant organism Bacteria then share or transfer their resistance genes with other bacteria -This can happen between patients for example through the provider's hands- HAND HYGEINE!

What should be done before initiating antiretroviral therapy?

A pregnancy test should be performed for those of childbearing potential prior to the initiation of antiretroviral therapy (AIII). Preliminary data have raised concerns about an increased risk of neural tube defects in infants born to people who were receiving DTG at the time of conception. Before prescribing DTG or another INSTI, please refer to Table 6b for specific recommendations on initiating these drugs as part of initial therapy

Which of the following groups require prophylaxis for IE with dental procedures? SELECT ALL that apply A. 56 yo male with a history of IE 5 years ago B. 90 yo male with a prosthetic valve replacement in the mitral position C. 25 yo male current IVDU D. 45 yo bone marrow transplant patient

A. 56 yo male with a history of IE 5 years ago B. 90 yo male with a prosthetic valve replacement in the mitral position

LM is 50-year old male living with HIV. He is a current IVDU and just moved into town trying to establish care. His current regimen includes Atripla® (efavirenz/tenofovir disoproxil fumarate/emtricitabine) x 6 months (started 3/1/2020). He is not on any other medications and has no other comorbidities. He is HLA-B*5701 positive and all other labs are WNL. However, he never received baseline resistance testing to antiretrovirals prior to starting Atripla. Most recent HIV treatment surrogate laboratory marker trends are depicted in table below: CD4 350 340 320 Viral load 16,000 2,000 6,000 1) Which one of the following statements below might explain LM's current CD4/VL trends while taking Atripla? Select all that apply. A. He shows an incomplete virologic response B. He has a declining overall CD4 cell count C. IVDU might play a role in reducing LM's adherence to Atripla D. If he gets genotypic resistance testing done today, a K103N mutation might be likely E. It is possible that LM may have acquired a resistant HIV viral strain when first infected with HIV (i.e. before starting Atripla)

A. He shows an incomplete virologic response Should have undetectable viral load after 6 months B. He has a declining overall CD4 cell count C. IVDU might play a role in reducing LM's adherence to Atripla D. If he gets genotypic resistance testing done today, a K103N mutation might be likely E. It is possible that LM may have acquired a resistant HIV viral strain when first infected with HIV (i.e. before starting Atripla)

Which of the following is the preferred treatment for uncomplicated cystitis? A. Nitrofurantoin B. Ciprofloxacin C. Amox/clav

A. Nitrofurantoin

Which of the following agents can be used to treat an initial episode of genital HSV? Select all. A: Acyclovir B: Valacyclovir C: Famiclovir

A: Acyclovir B: Valacyclovir C: Famiclovir Don't need to know doses

A patient with uncontrolled diabetes (last A1c 14%) presents to her primary care office with complaints of a "sinus infection". Upon physical examination, the physician sees black mold in her nasal passages. They suspect that this infection is caused by mucormycetes. Which of the following is the most appropriate treatment recommendation for this patient? A: Amphotericin B B: Flucytosine C: Voriconazole D: Micafungin

A: Amphotericin B

A patient (NKA) is admitted to the hospital for a perforated appendix and will have surgery performed immediately. Which of the following would be an appropriate empiric therapy recommendation for this patient? A: Cefoxitin B: Nitrofurantoin C: Nafcillin D: Doxycycline

A: Cefoxitin

Those who are clinically eligible for PrEP include following important characteristics? A: Documented negative HIV test B: No s/sx of acute HIV C: Normal renal function D: Documented HBV infection and vaccination status

A: Documented negative HIV test B: No s/sx of acute HIV C: Normal renal function D: Documented HBV infection and vaccination status

Which of the following 2 drug ART regimens are acceptable for Tx-naive PLWH? A: Dolutegravir + lamivudine B: Dolutegravir + rilpivirine C: Lopinavir/ritonavir D: Zidovudine + stavudine

A: Dolutegravir + lamivudine

New patients with HIV infection who have known K103N mutation should avoid initiating: A: Efavirenz B: Elvitegravir C: Rilpivirine D: Doravirine

A: Efavirenz

Which of the following ARVs are reserved for treatment experienced pts? A: Ertavirine B: Ibalizumab C: Enfuviritide d: Fostemsavir

A: Ertavirine B: Ibalizumab C: Enfuviritide D: Fostemsavir

Which is the MOST common presentation of HSV-2? A: Genital lesions B: Oral-labial lesions C: Diffuse pneumonitis D: Disseminated infection

A: Genital lesions- can cause oral lesion but this is the usual presentation B: Oral-labial lesions- HSV-1 is 90% oral HSV-2 and 10% genital

Which of the following are risk factors for MRSA for patients with a diabetic food infection? (If patients have any of these, make sure to include MRSA empiric activity) A: History of MRSA or colonization within the last year B: Frequent exposure of the foot to water C: Local prevalence of MRSA is high D: Warm climate

A: History of MRSA or colonization within the last year C: Local prevalence of MRSA is high

Which patient group is likely to be asymptomatically colonized with C. diff (up to 50%)? A: Infants and neonates B: Adolescents C: Adults > 65 years old D: Adults < 65 years old

A: Infants and neonates

What is a long-term complication of untreated Chlamydia infection? A: Infertility B: Anemia C: Insomnia D: Dysuria

A: Infertility B: Anemia- maybe if excessive bleeding, but not common or long-term D: Dysuria- presentation, not complication

Which agent is a preferred medication to add on for a MRSA activity in a patient with VAP? A: Linezolid B: Tigecycline C: Daptomycin D: Gentamicin

A: Linezolid Tigecycline- increased mortality Daptomycin also has MRSA activity gets inactivated in pulmonary surfactant

Adverse events of trimethoprim/sulfamethoxazole include the following: (select all that apply) A: Maculopapular rash B: Granulocytopenia C: Increased liver transaminases D: Hyperkalemia

A: Maculopapular rash B: Granulocytopenia C: Increased liver transaminases D: Hyperkalemia

Which of the following are key factors in the development of diabetic foot infections: A: Neuropathy, ischemia and immunological defects B: Neuropathy, poor foot care and perspiration C: Dry/scaly skin, negative probe test and proper fitting shoes D: Pseudomonas aeruginosa, MRSA and Group B Streptococcus

A: Neuropathy, ischemia and immunological defects

Which of the following antibiotics is recommended in a case of uncomplicated pancreatitis? A: None B: Ertapenem C: Cefoxitin D: Ciprofloxacin + metronidazole

A: None Reserved for severe cases... usually not infectious

Which of the following opportunistic infections requires primary prophylaxis? Select all that apply. A: PCP B: Toxoplasmosis C: Cryptococcal meningitis D: MAC

A: PCP B: Toxoplasmosis D: MAC PCP cut-off for primary prophylaxis is <200 CD4 Toxo <100 CD4 with positive IgG MAC <50 Cryptococcal meningitis- COIs= no primary prophylaxis

Which of the following is an appropriate empiric therapy regimen for a patient with healthcare associated intra-abdominal infection? A: Piperacillin/tazobactam B: Cefepime C: Ertapenem D: Cefazolin + metronidazole

A: Piperacillin/tazobactam Cefepime no b/c no anaerobic coverage Ertapenem and Cefazolin+metronidazole don't have pseudomonas coverage

A patient is being hospitalized and treated for cryptococcal meningitis. They have been started on liposomal amphotericin B IV daily and flucytosine QID for induction therapy. Which of the following two electrolytes need to be monitored and aggressively replaced while on treatment? A: Potassium and magnesium B: Calcium and potassium C: Calcium and magnesium D: Sodium and potassium

A: Potassium and magnesium

Which of the following is a Black Box Warning (BBW) associated with Clindamycin? A: Severe antibiotic associated colitis, including C. difficile colitis B: increased risk of serotonin syndrome, especially if combined with additional serotonergic agents C: Increased risk of tendon rupture D: Increased all cause mortality

A: Severe antibiotic associated colitis, including C. difficile colitis

Which of the following organisms is most commonly associated with purulent cellulitis? A: Staphylococcus aureus B: Staphylococcus epidermidis C: Streptococcus agalactiae (group B strep) D: Streptococcus pyogenes (group A strep)

A: Staphylococcus aureus

Which of the following is most commonly implicated in purulent cellulitis? A: Staphylococcus aureus B: Group A Streptococcus C: Pseudomonas aeruginosa D: Bacteroides spp

A: Staphylococcus aureus Same kind of variation for the exam except with gram positive cocci in clusters.

A patient is seen by his PCP for follow-up following I&D of a calf abscess. Upon examination, the wound is still red and oozing, despite adequate I&D. The abscess culture is growing 2+ Staphylococcus aureus (MRSA). Which of the following would be the most appropriate definitive treatment for this patient? The patient has NKA and good renal function. A: Sulfamethoxazole/trimethoprim B: Dicloxacillin C: Cephalexin D: Vancomycin

A: Sulfamethoxazole/trimethoprim Moderate purulent cellulitis Vanco if severe

A 23 year old patient comes to your community pharmacy counter for advice. She states that she has been experiencing pressure behind her cheeks and forehead for 12 days without improvement. She has been unable to blow her nose and states that "everything feels stuck in my head." Two days ago she also developed a sore throat. She is afebrile. Which of the patient's symptoms are associated with increased likelihood for bacterial rhinosinusitis and not a viral infection? Select all that apply A: Symptoms lasting > 10 days B: Afebrile C: Lack of improvement in symptoms D: Sore throat E: Nasal congestion

A: Symptoms lasting > 10 days C: Lack of improvement in symptoms

Which of the following medications can be used for both PCP AND toxoplasmosis primary prophylaxis? A: Trimethoprim/sulfamethoxazole B: Dapsone C: Aerosolized pentamidine D: Fluconazole

A: Trimethoprim/sulfamethoxazole

Which of the following is first line therapy for inital CDI, non-severe? Select all A: Vancomycin PO B: Metronidazole PO C: Vancomycin + metronidazole D: Fidaxomicin PO

A: Vancomycin PO D: Fidaxomicin PO

What are the therapeutic uses for Glyco/lipo?

ABSSTIs (all agents) Vancomycin - drug of choice for MRSA Daptomycin is bound by pulmonary surfactant, making it inactive - DO NOT use to treat PNA (pneumonia)!

What are the ADEs/monitoring for beta lactams?

ADE: All beta-lactams have the following possibilities Hypersensitivity reactions (spectrum) Seizures (variable, usually at high doses and not cleared appropriately like no renal dose adjustments) Monitoring: Renal function (if renally excreted)

What is the ARV POTENCY VERSUS GENETIC BARRIER TO RESISTANCE?

ARVs appearing together in the same ellipse should be considered to have roughly equivalent potencies and genetic barriers to resistance. -Bictegravir is similar to DTG in potency and genetic barrier to resistance

What other groups do we screen and treat? Why?

ASB, renal stone removal, TURP

What are the Effects of RTV Boosted PIs on Other Drugs?

ATV/r, DRV/r, LPV/r, TPV/r all decrease warfarin

What are the Boosted PIs/Contraindications?

ATV/r, DRV/r, LPV/r, TPV/r all with 1. Rifampin/Rifapentine 2. Lovastatin/simvastatin 3. St. John's Wort 4. Clopidogrel

What is the Outpatient Antimicrobial Therapy (OPAT)?

Ability to travel Cognitive ability Insurance coverage IVDU hx Consideration of antibiotic therapy - Stability - Number of doses/day

What are the Required ABSSSIs?

Abscesses Cellulitis Necrotizing fasciitis Diabetic foot infections

What are the General Principles of STI treatment?

Abstain from sex until they and their sex partners are treated Testing for other STIs including HIV should be performed Pregnant women should be screened and treated for STIs during pregnancy

How is Prostatitis classified?

Acute < 3 months of symptoms Chronic > 3 months of symptoms Chronic pelvic pain syndrome Urogenital pain, lower tract symptoms (voiding or storage), psychological issues and sexual dysfunction

What is the treatment for encephalitis?

Acyclovir 10 mg/kg q 8 hour for herpes (HSV) Ideal or adjusted body weight if > 20% IBW - Renally dose adjusted because it can cause crystals in renal tubules which leads to renal damage and failure

What is the empiric viral treatment for meningitis?

Acyclovir 10 mg/kg q 8 hr IBW and renally adjusted for herpes Definitive- based off CSF results

What are the Risk Factors for Acquisition of C diff?

Advanced age: > 65 years old Duration of hospitalization, Increases with length of stay Antimicrobial use Multiple agents Duration of therapy Chemotherapy GI surgery Manipulation of GI tract Acid suppressive therapy

What are the adverse effects of TMP/SMX?

Adverse effects (20 - 85% of patients with HIV) *Rash* Fever Leukopenia Thrombocytopenia Azotemia Hepatitis Hyperkalemia Management of rash Can be treated through with antihistamines If using for ppx, can stop and reintroduce at a lower dose or reduced frequency DO NOT rechallenge patients with Steven Johnson's syndrome (SJS) or toxic epidermal necrolysis (TEN), ever!

What are the Flucytosine ADEs?

Adverse effects: *Concentration-dependent bone marrow suppression (anemia, neutropenia, thrombocytopenia)* Diarrhea, nausea, vomiting Rash Hepatotoxicity

What are the Rifabutin ADEs?

Adverse effects: *Hepatotoxicity* Uveitis (dose dependent) *Red-orange discoloration of body fluids* Rash Arthralgia Neutropenia *GI: Nausea, vomiting, abdominal pain, diarrhea, anorexia*

What are the Amphotericin B ADEs?

Adverse effects: *Nephrotoxicity* *Infusion-related reactions (fever, chills, rigors, back pain, hypotension)* *Hypokalemia and hypomagnesemia* Anemia Thrombophlebitis Nausea, vomiting Liposomal formulations have lower incidence of nephrotoxicity and infusion-related reactions

What are the Bacteria in a brain/epidural Abscess?

Aerobic: Streptococcus spp, Staphylococcus spp, Enterobacterales Anaerobic: Prevotellaspp, Bacteroides spp

What are the Oxazolidinones?

Agents: Linezolid (older, preferred) and tedizolid (newer) MOA: Binds to 50S subunit on the ribosome, prevents stable formation of 70S complex and prevents translation Different than other protein synthesis inhibitors

What are the aminoglycosides (AGs)?

Agents: amikacin, gentamicin, tobramycin and plazomicin MOA: Bind to 30S subunit on the ribosome resulting in misreading of the genetic code and eventual cell death

What are the aminopenicillins?

Agents: amoxicillin (PO), ampicillin (IV *Also PO but bioavailability is poor*) Drug of choice for susceptible Enterococci - Also have Streptococci activity

What are the macrolides?

Agents: azithromycin, erythromycin and clarithromycin MOA: Bind to 50S subunit of the ribosome disrupting normal bacterial protein synthesis

What are the therapeutic uses for monobactams?

Agents: aztreonam Reliable activity against Pseudomonas aeruginosa and other Gram negatives Used for beta-lactam allergic patients

What are the fluoroquinolones and MOA?

Agents: ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin, delafloxacin MOA: Inhibit DNA topoisomerase II (aka DNA gyrase) and IV, blocking DNA replication and resulting in bacterial cell death

What are the Polymixins?

Agents: colistin and polymyxin B MOA: bind to outer membrane, leading to membrane disruption and leaking of cellular contents Therapeutic uses: used in combination for infections caused by *multidrug resistant Gram negative pathogens*

What are the tetracyclines (TCNs)?

Agents: doxycycline, minocycline, tetracycline, omadacycline, eravacycline and tigecycline (a glycylcycline, souped up version of minocycline) MOA: Bind to 30S subunit of the ribosome inhibiting protein synthesis

What are the natural penicillins?

Agents: penicillin G (IV) and penicillin V (oral) 1. Penicillin G Drug of choice for syphilis 2. Penicillin V Susceptible strep infections (ie pharyngitis caused by Group A Strep)

What are the glyco/lipopeptides?

Agents: vancomycin, daptomycin, dalbavancin, oritavancin and telavancin MOA: Vancomycin - bind D-ala-D-ala precursors of peptidoglycan Daptomycin - Binds to bacterial cell membranes and causes cell death via rapid depolarization of the membrane potential Oritavancin/dalbavancin - Both inhibit cell wall synthesis , dalbavancin also causes destabilization of cell membrane - loss of membrane potential Telavancin - inhibits cell wall synthesis

What is a Fecal Microbiota Transplant (FMT)?

Aka fecal transplant Different routes of administration Varying protocols Higher success rate than medications

What is Pediculosis Pubis?

Aka pubic lice, crabs Usually transmitted by sexual contact Signs/symptoms Pruritus Lice or nits on pubic hair

What is viral meningitis?

Also known as aseptic Common causes: enteroviruses, HSV-2, HIV, other viruses Diagnosis: PCR of CSF

What are the AmB Dosing Strategies?

AmB formulations are NOT interchangeable ISMP recommends ordering using brand names Ablecet (AmB Lipid Complex) Amphotec (AmB Cholesteryl Sulfate Complex) Ambisome (AmB Liposome) Fungizone (AmB deoxycholate) TDM is not necessary

What covers MSSA, Streptococcus spp, and Enterococcus faecalis?

Amox/clav Amp/sulb Pip/tazo Imipenem/cila +/- rele Delafloxacin (5) Ervacycline Omadcycline Tigecycline All glyco/lipopeptides (3) Linezolid/Tedizolid 3-Includes: vancomycin, teicoplanin, telavancin, oritavancin, dalbavancin and daptomycin. Daptomycin has activity against MSSA, E. faecalis and most Strept species but is NOT reliable against S. pneumo or VGS 5- Levofloxacin, moxifloxacin and gatifloxacin technically have activity against MSSA and Enterococcus faecalis, however these SHOULD NOT be used to treat infections caused by these bacteria

What are the Oral Beta-lactams for a UTI?

Amox/clav, cefaclor, cefdinir, cefpodoxime and ceftriaxone Alternative therapy due to lower efficacy than FQ or SMX/TMP Common side effects: diarrhea, nausea, vomiting, rash and urticaria

What is Antimicrobial Stewardship?

An ongoing effort by a health care institution to optimize antibiotic use among hospitalized patients in order to improve patient outcomes, ensure cost-effective therapy and reduce adverse sequelae of antibiotic use

Which of the following is an appropriate empiric regimen for a patient with suspected viral meningitis? A: No treatment indicated for viral meningitis B: Acyclovir 10 mg/kg (ideal body weight) IV q 8 hr C: Acyclovir 10 mg/kg (actual body weight) IV q 8 hr D: Acyclovir 10 mg/kg (adjusted body weight) IV q 8 h

Answer: evaluate body weight, can be B, C or D Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.

What are the ADEs/monitoring for Pencillins

Anti-staph: maybe higher acute interstitial nephritis (monitor kidney function) Aminopenicillins: higher incidence of GI upset (ie diarrhea) All others have similar ADE profile as rest of beta-lactams

What is a PCN Allergy?

Antibiotics are frequently reported as allergies 1 - 15% of patients report an PCN allergy True incidence of PCN anaphylaxis is 0.004% - 0.015% Patients with PCN allergies get more Antibiotics (vanco, FQ and clinda) C diff, MRSA and VRE infections Longer length of stay

What is Amputation with PJI?

Antibiotics are indicated for 24 - 48 hours after amputation if all infected tissue is removed If not, needs 4 - 6 weeks for treatment If patient is septic, needs longer treatment

You are the clinical pharmacist that is responsible for the general medical unit. A patient was admitted to the hospital last night with a respiratory tract infection. Demographics: 67 yo male, ht 70 inches, wt 89 kg, NKA. Past medical history: diabetes, hypertension, coronary artery disease Labs/vitals: WBC 17 (bands 9%), scr 1.3, temp 100.5 F, HR 100, BP 110/60, RR 22 Imaging: Right lower lobe infiltrate

Assessment: Staph pneumoniae most common probably CAP Plan: Vanco or ceftriaxone Comes back gram negative rods Now: Cannot do aminoglycoside as functional monotherapy (the other thing doesnt cover the bug) So Cefepime

What is the empiric treatment for PJI?

Avoid administering antimicrobials until cultures have been obtained and a diagnosis established Unless patient critically ill

What are the Macrolides for CABP?

Azithromycin 500 mg on first day, then 250 mg daily (outpatient dosing) 500 mg daily (inpatient dosing) Clarithromycin 500 mg twice daily ER 1000mg daily

Which of the following is a common cause of CABP? A Anaerobic Gram negatives B Atypical bacteria C Aspergillosis fumigatus D Pseudomonas aeruginosa

B Atypical bacteria D is for HAP

Which type of organism stains pink or red on a Gram stain? A Gram positive B Gram negative C Acid fast organisms D Atypical organisms

B Gram negative

What does Streptococcus pneumoniae look like on a Gram stain? A Gram negative bacilli B Gram positive cocci in pairs and chains C Gram positive coccobacilli D Gram positive bacilli

B Gram positive cocci in pairs and chains Causes meningitis

DV is a 48-year old female recently diagnosed with HIV a couple of months ago. She also was recently diagnosed with hyperlipidemia and was prescribed simvastatin. Other PMH includes GERD, depression, hypertension, type-2 diabetes mellitus, and chronic kidney disease. Most recent labs: CD4 660 cells/mm3, HIV viral load 92,500 copies/mL, creatinine clearance 65 mL/min, A1c 7%, HLA-B*5701 testing negative, and baseline genotypic resistance testing shows only K103N mutation. Vitals from today's visit: BP 118/78, RR 12, HR 70 SH: unremarkable Current Medication List: · Metformin 500 mg twice daily · Sertraline 200 mg once daily · Simvastatin 20 mg QHS · Lisinopril 10 mg once daily · Lansoprazole 30 mg once daily every morning · Cholecalciferol 2000 IU/day · Calcium carbonate 1250mg/day Given all the patient information described above, which one of the following antiretroviral regimens would be the MOST appropriate choice for DV? Select all that apply. A. Genvoya® (elvitegravir/cobicistat/TAF/emtricitabine) 1 tablet once daily B. Triumeq® (dolutegravir/abacavir/lamivudine) 1 tablet once daily C. Symfi® (efavirenz/TDF/lamivudine) 1 tablet QHS on an empty stomach D. Symtuza® (darunavir/cobicistat/TAF/emtricitabine) 1 tablet once daily w/ food E. Biktarvy® (bictegravir/TAF/emtricitabine) 1 tablet once daily F. Delstrigo® (doravirine/TDF/lamivudine) 1 tablet once daily G. Odefsey® (rilpivirine/TAF/emtricitabine) 1 tablet once daily H. Descovy® (TAF/emtricitabine) 1 tablet once daily and Evotaz® (atazanavir/cobicistat) 1 tablet once daily

B. Triumeq® (dolutegravir/abacavir/lamivudine) 1 tablet once daily E. Biktarvy® (bictegravir/TAF/emtricitabine) 1 tablet once daily F. Delstrigo® (doravirine/TDF/lamivudine) 1 tablet once daily rilpivirine DDI with lansoprazole TAF over TDF because of CKD cobicistat CI with simvastatin Abacavir okay with HLA-B5701 negative *K103N=CANNOT USE EFAVIRENZ* *RILPIVIRINE>100,000 CANNOT USE IT* *HLAB5701 TESTING POSITIVE=CANNOT USE ABACAVIR*

Which of the following is MOST likely to have their episode of epididymitis cause by ENTERIC pathogens only? A: 65 yo male with BPH and bacteriuria B: 24 yo MSM, insertive partner in anal sex C: 30 yo male with female partners only

B: 24 yo MSM, insertive partner in anal sex

Duration of therapy for intra-abdominal infection depends MAINLY on the following: A: Patient risk factors for infection B: Adequate source control C: Organism isolated D: All of the above

B: Adequate source control

Clostridiodes difficile is __________________(fill in the blank, select all that apply) A: Aerobic B: Anaerobic C: Spore-forming D: Bacilli E: Gram negative F: Cocci G: Gram positive

B: Anaerobic C: Spore-forming D: Bacilli G: Gram positive

Clostridioides difficile is a A: Anaerobic, Gram negative rod B: Anaerobic, Gram positive rod C: Aerobic, Gram negative cocci D: Aerobic, Gram positive cocci

B: Anaerobic, Gram positive rod

A patient is admitted for suspected intra-abdominal infection. An exploratory surgery is performed. The patient received a partial dissection of their small intestine including an anastomosis. Two days after the surgery, the patient developed fever, elevated WBC and increasing abdominal pain. Blood cultures were drawn and the patient was started empirically on imipenem/cilastatin. Two days later, their blood cultures are positive with the following organisms: 1. Bacteroides fragilis 4/4 bottles, both sets positive, susceptible to all antibiotics tested 2. Enterococcus faecalis 4/4 bottles, both sets positive, susceptible to all antibiotics tested Which of the following would be the most appropriate definitive therapy for this patient? A: Add vancomycin to imipenem/cilastatin B: Discontinue imipenem/cilastatin and start ampicillin/sulbactam C: Add gentamicin to imipenem/cilastatin D: No modification to current imipenem/cilastatin therapy needed

B: Discontinue imipenem/cilastatin and start ampicillin/sulbactam Need gram + coverage and anaerobic coverage

Common Gram negative pathogen implicated in community acquired intra-abdominal infection include: A: Enterococcus spp B: E. coli C: Bacillus cereus D: Clostrdioides difficle

B: E. coli

Which of the following is most commonly implicated in non-purulent cellulitis? A: Staphylococcus aureus B: Group A Streptococcus C: Pseudomonas aeruginosa D: Bacteroides spp

B: Group A Streptococcus Variation for exam: Patient case. diagnosed with cellulitis-figure out purulent or non-purulent. Given gram stain of gram + cocci in pairs and chains. Pick organism.

A 65 year old patient with HIV (CD4 count 146 cells/mm3), sulfa allergy = anaphylaxis, presents for a follow-up visit for his HIV management. The physician decides to start PCP prophylaxis with dapsone. Which of the following best describes the rationale for order G6PD testing prior to starting prophylaxis? A: He may have an increased risk of liver toxicity B: He may develop hemolytic anemia with dapsone C: He is more prone to develop a severe rash D: He may have increasingly more CYP450 drug interactions

B: He may develop hemolytic anemia with dapsone

Which of the following is an appropriate counseling point for non-antimicrobial prevention of urinary tract infections? A: Cranberry extract is very effective in treating asymptomatic bacteriuria during pregnancy B: Lactobacillus spp may be beneficial in post-menopausal women to prevent recurrent UTIs C: Oral estrogen use decreases the likelihood of UTIs in post-menopausal women

B: Lactobacillus spp may be beneficial in post-menopausal women to prevent recurrent UTIs

Which is one of the common bacterial pathogens causing acute otitis media? A: Pseudomonas Aeruginosa B: Moraxella catarrhalis C: Mycoplasma pneumoniae D: Staphylococcus aureus

B: Moraxella catarrhalis

A 38 y/o man presents for care with newly diagnosed HIV infection. He currently takes no medications, has no respiratory symptoms and his physical examination is unremarkable. He has a CD4 count of 214 cells/mm3 and is positive for the IgG Toxoplasma antibody. Prophylaxis for which opportunistic infection (OI) is indicated for this patient? Select all that apply. A: Toxoplasmosis B: None indicated C: PCP D: MAC E: Cryptococcus

B: None indicated

Which pneumonia vaccine is recommended in adults who smoke for ages 19 - 64 years old? A: PCV13 B: PPSV23 C: Both PPSV23 and PCV13 D: Neither vaccine

B: PPSV23

What is the definition of hospital acquired pneumonia, HAP? A: Pnuemonia developing any time during hospitalization B: Pneumonia developing > 48 hours after hospital admission, not present on admission C: Pneumonia developing in a nursing home resident D: All fit the definition of HAP

B: Pneumonia developing > 48 hours after hospital admission, not present on admission

Which of the following are MOST commonly associated with bacterial vaginosis? Select all. A: Lactobacilli B: Prevotella C: Gardenella vaginalis D: Group B strep

B: Prevotella C: Gardenella vaginalis D: Group B strep- normal flora but not implicated in BV

Which of the following INSTIs are recommended initially for most people with HIV? A: Elvitegravir B: Raltegravir C: Dolutegravir D: Bictegravir

B: Raltegravir C: Dolutegravir D: Bictegravir

Which of the following is/are true statements? Select all that apply A: Rifabutin 150 mg PO TIW is appropriate with efavirenz use B: Rifabutin 150 mg daily is appropriate with boosted PIs C: Clarithromycin 500 mg PO BID and ethambutol 15 mg/kg/day are considered a preferred treatment regimen for MAC infection D: Treatment of MAC infection is usually 6 months E: Primary prophylaxis for MAC is CD4 < 100

B: Rifabutin 150 mg daily is appropriate with boosted PIs C: Clarithromycin 500 mg PO BID and ethambutol 15 mg/kg/day are considered a preferred treatment regimen for MAC infection

Which organism(s) is/are a common cause of community acquired bacterial meningitis in patients over 50 years old? Select all that apply. A: Streptococcus agalactiae B: Streptococcus pneumoniae C: Haemophilus pneumoniae D: Listeria monocytogenes

B: Streptococcus pneumoniae D: Listeria monocytogenes Think of agalactiae as birth canal

DM is a treatment-naïve 55 YO female with HIV who presents to the clinic for an initial visit. DM has osteopenia and smokes 1 PPD. Most current VL is 120,000 copies/mL and CD4 cell count is 450 cells/mm3. HLA-B*5701 testing positive. Genotypic resistance testing shows no mutations and all other labs WNL. Other current medications DM is taking includes calcium/vitamin D supplementation. What is the MOST appropriate ARV treatment regimen for DM? A: TDF/FTC + dolutegravir B: TAF/FTC + bictegravir C: ABC/3TC + dolutegravir D: TAF/FTC + rilpivirine E: TDF/3TC + doravirine

B: TAF/FTC + bictegravir HLA-B positive= no abacavir Avoid TDF for bone death *Viral load > 100k and PPI so no rilpivirine*

You work at a community pharmacy and have a collaborative practice agreement with a physician which allows you to perform screening for GAS pharyngitis with rapid antigen detection test (RADT). You perform a RADT on a fifteen year old patient with complaints of a very sore throat for 2 days. The GAS RADT comes back positive. What does this mean? A: The patient should be sent to the physician for a GAS culture swab to be performed B: The patient should be prescribed amoxicillin C: The patient should be prescribed cephalexin D: The patient should be prescribed ciprofloxacin E: The patient should be sent to the physician for anti-streptococcal antibody titers

B: The patient should be prescribed amoxicillin

A 50 year old male presents to the ED with fever of unknown origin. PMH includes bioprosthetic valve replacement 2 months ago. A TEE is done and confirms vegetations on his prosthetic valve. Blood cultures are done prior to starting antibiotic therapy. Which of the following is an appropriate empiric therapy regimen to start while awaiting blood culture results? A: Vancomycin and daptomycin B: Vancomycin, gentamicin and rifampin C: Vancomycin and gentamicin D: Vancomycin and ceftriaxone

B: Vancomycin, gentamicin and rifampin

Which of the following are common adverse effects associated with voriconazole therapy? A: Neutropenia and nephrotoxicity B: Visual disturbances and hepatotoxicity C: Infusion-related reactions of fever and rigors D: Hypokalemia and hypomagnesemia

B: Visual disturbances and hepatotoxicity

What is the Definitive Abx Treatment for PJI?

Based on culture results Length based on surgical procedure 1. MSSA/MSSE (Methicillin susceptible Staphylococcus epidermidis) (Naf/oxa or cefazolin) + rif *then FQ* 1 Stage: x 3 mo 2 Stage: x 4-6 wk 2. MRSA/MRSE Vanco + rif *then FQ* 1 Stage: x 3 mo 2 Stage: x 4-6 wk 3. Streptococci Pen G or ceftriaxone x 4 - 6 wk 4. Enterococci Amp or PCN x 4 - 6 wk 5. GNB Erta or ceftriaxone or cefepime x 4 - 6 wk 6. P. aeurginosa (cefepime or meropenem) + tobra x 4 - 6 wk

What is the DFI Treatment Duration?

Based on severity of infection Mild: 1 - 2 weeks Moderate or Severe: 2 - 3 weeks

How can UTIs be prevented?

Behavioral changes are recommended Intercourse counseling: Abstinence or reduction in frequency Avoid spermicides Urinate soon after intercourse Other behaviors: Don't delay urination, drink plenty of fluids, wipe front to back, avoid tight fitting underwear, avoid douching Antibiotic ppx

What are some important counseling points that you can give this patient to reduce her risk of UTIs in the future?

Behavioral changes are recommended Intercourse counseling: Abstinence or reduction in frequency Avoid spermicides Urinate soon after intercourse Other behaviors: Don't delay urination, drink plenty of fluids, wipe front to back, avoid tight fitting underwear, avoid douching Antibiotic ppx

How many blood cultures should you get?

Blood cultures are always ONE set of TWO bottles - one is aerobic and one is anaerobic TWO sets of cultures should always be obtained One set from two different sites Total= 2 cultures, 4 bottles Contamination occurs frequently Patient considerations If contaminating organism present, consider patient conditions and risk factors

On day 1, L.S. has transthoracic echocardiography, which reveals a 0.7-cm vegetation on her tricuspid valve. The hospitalist is also reviewing the culture and susceptibility report and notices that the E. faecium culture report indicates an MIC of ≥ 500 mcg/ mL to gentamicin and ≥ 2000 mcg/mL for streptomycin. Which one of the following is best to recommend for L.S.? A.Continue the antibiotic selected above with no changes B. Add gentamicin to the regimen for synergy C.Add streptomycin to the regimen for synergy D. Discontinue the above regimen and start imipenem/cilastatin

Both of those are high A.Continue the antibiotic selected above with no changes

What is the Community Acquired High Risk treatment for intra-abdominal infections?

Broad spectrum Gram negative activity recommended Do not use FQ unless E. coli susceptibilities > 90% Routine AG use or double Gram negative activity is not recommended unless MDR pathogen likely Empiric activity against Enterococcus may be considered Do not need MRSA or antifungal in the absence of evidence of infection caused by MRSA or yeast High risk or severity, severe physiologic disturbance, advanced age or immunocompromised 1. Single agent Imipenem-cilastatin, meropenem, doripenem and piperacillin/tazobactam 2. Combination Cefepime, ceftazidime, ciprofloxacin or levofloxacin PLUS Metronidazole

What are the therapeutic uses for TCNs?

Broad spectrum: Respiratory tract infections, tick-borne illnesses, ABSSSIs (acute bacterial skin and skin structure infections), STIs, intra-abdominal infections (tigecycline and ervacycline) -Minocycline and doxycycline more clinically used due to lipophilicity compared to tetracycline, so they have increased bioavailability and higher efficacy -Minocycline is used for acne -Doxycycline has gotten more expensive

Which of the following is an anaerobic organism? A Chamydophila pneumoniae B Bacillus cereus C Bacteroides spp D Neisseria gonorrhoeae

C Bacteroides spp A is atypical B is gram positive D is gram neg

Which of the following organisms represents an increased risk in patients with decreased cell mediated immunity, such as the very young and very old? A Neisseria meningitidis B Staphylcoccus aureus C Listeria monocytogenes D Streptococcus pneumoniae

C Listeria monocytogenes

65 yo female presents with nausea, vomiting and abdominal pain PMH: frequent UTIs, DM, CAD Labs: CBC: WBC 10.6 x 10^3 cells/mL, Hbg 11 gm/dL, Hct 34 %, PLT 171 x 10^3 cells/mL Chem 7: Na 141 mEq/L, K 3.9 mEq/mL, Cl 111 mEq/mL, CO2 18, BUN 27 g/dL, Scr 1.1 g/dL, Gluc 212 UA: WBC 5 -10 HPF, RBC 2 -5 HPF Admitted with abdominal pain Started on ciprofloxacin for positive UA Complained of increasing abdominal pain and discomfort, started having loose stools (3 per 8 hour shift) C difficile toxin + in stools Classify this patient's infection Recommend initial treatment for this patient based on her severity of illness What other things to you want to do for this patient?

C diff Stop Cipro Begin Vanco

RT is a 70 yo male who presented to the ED with a 2 day history of increasing shortness of breath PMH: COPD, DM and HTN Pt became very lethargic with increasing shortness of breath, was intubated for airway protection, started on vasopressors for sepsis and admitted to the ICU Imaging revealed a left lung infiltrate and the patient was started on antibiotics for community acquired pneumonia On day 3 of hospital admission, he was noted to spike a fever and have 4 loose bowel movements in the last 12 hours A stool sample was sent and came back positive for toxogenic C diff What additional information would you like to know? Classify this patient's infection Recommend initial treatment for this patient What additional monitoring/follow-up do you recommend for this patient?

C diff- initial, fulminant (septic shock on pressors) Vanco- PO for CDI IV is for Sepsis NO IV VANCO FOR C DIFF Don't DC her Levofloxacin but decrease course of ABX

L.S. is a 68-year-old woman who is receiving hemodialysis for end-stage kidney disease secondary to poorly controlled diabetes Home meds: insulin glargine, insulin aspart, paroxetine, and metoprolol She presents for one of her three weekly dialysis sessions and complains of fever, chills, and loss of appetite over the past 2 days. Examination results are: temperature 39ºC (102.2ºF), respiratory rate 21 breaths/ minute, heart rate 103 beats/minute, and blood pressure 96/52 mm Hg. Upon auscultation, a grade 3/ 6 systolic murmur is detected. L.S. is transferred to the hospital and admitted with suspected sepsis. Therapy is initiated with vancomycin and ceftriaxone. Multiple blood cultures drawn on admission later reveal Enterococcus faecium with an MIC to vancomycin of 32 mcg/mL. Which of the following would best treat L.S. infection after the culture and susceptibility results are known? A. Ceftaroline B. Linezolid C. Daptomycin D. Meropenem

C. Daptomycin Treatment for VRE B and C both have activity for VRE Prolonged treatment may lead to anemia/thrombocytopenia with Linezolid and pt is on hemodialysis

K.P. is a 33-year-old man; he has been a quadriplegic since receiving a gunshot wound at the age of 18. NKDA He reports foul odor from a sacral wound upon dressing changes and overall feeling unwell Vitals on admission included temperature 38.5°C, heart rate 111 beats/minute, blood pressure 95/62 mm Hg; laboratory tests results include WBC 18.1 x 103 cells/mm3 . Physical examination reveals a large foul-smelling sacral decubitus ulcer. Chart review reveals K.P. has a history of ESBL-producing Enterobacter aerogenes and MRSA from the wound Which one of the following combination regimens is best to recommend for K.P.? A. Ceftriaxone and daptomycin B. Piperacillin/tazobactam and vancomycin C. Meropenem and daptomycin D. Ciprofloxacin and minocycline

C. Meropenem and daptomycin

1) Assuming LM's potential adherence barriers (i.e. IVDU) are resolved and F/U resistance testing shows only a K103N mutation, which one of the following ARV regimens might be the MOST appropriate choice for LM? Select all that apply. A. Triumeq® (dolutegravir/abacavir/lamivudine) 1 tablet once daily B. SymfiLo® (efavirenz/tenofovir disoproxil fumarate/lamivudine) 1 tablet QHS on an empty stomach C. Symtuza® (darunavir/cobicistat/tenofovir alafenamide/emtricitabine) 1 tablet once daily w/ food D. Biktarvy® (bictegravir/tenofovir alafenamide/emtricitabine) 1 tablet once daily

C. Symtuza® (darunavir/cobicistat/tenofovir alafenamide/emtricitabine) 1 tablet once daily w/ food D. Biktarvy® (bictegravir/tenofovir alafenamide/emtricitabine) 1 tablet once daily HLA means no abacavir K103N means no efavirenz

In general, when positive, which of the following types cultures is MOST beneficial to tailor antibiotic therapy for ABSSSIs? a. Superficial wound cultures b. Aspirated fluid c. Blood d. CSF

C. blood

What is the CDI: Background?

C. difficile is a Gram-positive, anaerobic, spore-forming bacillus Implicated in 15-25 % of antibiotic associated diarrhea Spread by fecal-oral route

What are Cryptococcosis?

C. neoformans - pigeon guano & rotting trees C. gattii - eucalyptus & coniferous trees Can colonize without disease Pathogenesis dependent on host defense, virulence of strain and inoculum size

What is the minimum interval between two PPSV23 vaccinations? A: 8 weeks B: 1 year C: 5 years D: 10 years

C: 5 years

What is the duration of antibiotic treatment for cellulitis? A: None, no antibiotics are indicated B: 14 days C: 5-7 days based on patient response D: 21 days

C: 5-7 days based on patient response

You work in an outpatient clinic. Dr. Herring, one of the medical residents, asks you for advice on what antibiotic is best for her 3-year old patient. Dr. Herring tells you the patient has had a fever and otalgia for 2 days and has been very irritable. Dr. Herring performed an otoscopic exam and confirmed that the child has acute otitis media (AOM). The child's past medical history is significant for asthma and this is the child's second episode of AOM, with the last being 12 months ago. The child experienced an anaphylactic reaction when treated with amoxicillin for the first AOM episode. What is the most appropriate medication for this child's AOM? A: Augmentin B: Bactrim C: Azithromycin D: Cefdinir

C: Azithromycin

Which of the following STIs is commonly present in a patient with Gonorrhea? (high rate of co-infection of Gonorrhea and this STI) A: HSV B: HPV C: Chlamydia D: Syphilis

C: Chlamydia Have gonorrhea, treat for gonorrhea and chlamydia Have chlamydia, test for gonorrhea

You are a community pharmacist. A 33 year old transgender woman presents to your pharmacy counter. She reports she has been coughing for a week and now she has started to coughing up some 'stuff'. She has also had a mild fever (99.8 F) and she gets headaches after coughing spells. She is not sure whether she should go to urgent care or what they might be able to do for her. What do you recommend to this patient? A: Go to urgent care - they will be able to give you albuterol which will help your breathing B: Go to urgent care- they should prescribe you an antibiotic to get rid of your cough C: Don't go to urgent care, try some ibuprofen or acetaminophen for your headache D: Don't go to urgent care, coughs usually resolve within 10 days, so you should be feeling better soon.

C: Don't go to urgent care, try some ibuprofen or acetaminophen for your headache

An 85 year female is admitted to the hospital with LLQ pain, anorexia, fever and hemtochezia. She has a PMH positive for rheumatoid arthritis for which she takes weekly methotrexate. She is diagnosed with acute diverticulitis. Which of the following is the most appropriate classification of her intra-abdominal infection? A: Healthcare associated B: Mild/moderate community acquired C: High risk/severity community acquired

C: High risk/severity community acquired

A patient is started to imipenem/cilastatin for a healthcare associated intra-abdominal infection. Which of the following would be the most appropriate monitoring parameter for this patient? A: LFTs B: EEG C: Renal function D: CPK

C: Renal function

Which is NOT a component of the CURB-65 score? A: Confusion B: Uremia C: Rhabdomyolysis D: Blood pressure

C: Rhabdomyolysis Won't need to calculate on the exam

Which of the following is a Gram positive pathogen in community acquired intra-abdominal infection? A: E. coli B: Bacteroides spp C: Streptococcus spp D: Staphylococcus aureus

C: Streptococcus spp

What is the purpose of using leucovorin with pyrimethamine for treatment of toxoplasmosis? A: To increase serum potassium levels B: To prevent pyrimethamine associated nausea C: To prevent hematological toxicities associated with pyrimethamine D: To increase CD4 cell counts

C: To prevent hematological toxicities associated with pyrimethamine

A patient is diagnosed with necrotizing fasciitis. Which of the following would be an appropriate empiric therapy recommendation (in addition to immediate surgical intervention)? A: Dicloxacillin B: Sulfamethoxazole/trimethoprim C: Vancomycin + piperacillin/tazobactam D: Penicillin

C: Vancomycin + piperacillin/tazobactam

Select all that apply. Patients with Penicillin allergies are more likely to receive ________than patients without a pencillin allergy: A: Lower healthcare costs B: C. difficile, MRSA and Pseudomonas infections C: broad spectrum antibiotics D: longer length of stay

C: broad spectrum antibiotics D: longer length of stay

Day 1: RR, 64-year-old women who lives in a skilled nursing facility is admitted into the ICU for a hip fracture. RR has history of IV abx exposure two weeks ago from treating her pneumonia. Indwelling urinary catheter in place. Urine cultures are ordered. She is symptomatic. How would you classify this patient's infection? What are the common organisms implicated in this type of infection? Recommend an appropriate empiric therapy for this patient

CA-UTI E coli Proteus mirabilis Kleb Staph saprophyticus PLUS Providencia stuartii Corynebacterium Morganella Empiric: Meropenem 1 gm IV q 8 hours for 7 days with prompt resolution

What is some CABP Background?

CABP + influenza is the 7th leading cause of death in the US ~900,000 episodes of CABP occur in adults ≥ 65 years

What are Resistance Reports?

CDC Threat Report Urgent, serious, concerning White House National Action Plan Joint Commission Stewardship recommendations

How is healthcare associated ventriculitis and meningitis diagnosed?

CSF cultures are the most important test to establish the diagnosis of healthcare associated ventriculitis and meningitis - Shunt, reservoir or drain - Negative culture does not rule out infection

CC: "I have been coughing, with chest pain and trouble breathing for a few days" HPI: a 45 year old male presents to the ED with fever, cough, chest pain that worsens with breathing or coughing, and SOB. Has had for 3 days now. PMH: none Surgical Hx: none FH: father has HTN, mother has diabetes SH: single, no smoking or illicit drugs, drinks occasionally on weekends Allergies: NKA Home medications: None Up to date on vaccines Vitals: temp 101.0 deg F, HR 110, RR 31, BP 125/75, O2 89%, ht 69 in, 75 kg General: moderate distress HEENT: WNL Pulm: diminished breath sounds, crackles bilaterally CV: WNL Abdominal: hyperactive bowel sounds Neuro: AOx4 Extremities: WNL Labs: Abnormal: WBC 18 X 10^3 cells/mL, PCT 0.8 mcg/L All others normal: Scr 0.9 mg/dL, BUN 20 mg/dL CXR: Consolidation, pleural effusions present Cultures: Blood, sputum- pending Assessment: What is this patient's CURB 65 score? What does that mean? How would you classify this patient's infection? What supports that diagnosis What is (are) the most likely bacteria responsible for this patient's infection? Plan: Select an appropriate empiric regimen for this patient Make sure to include appropriate monitoring parameters

CURB-65 score: 2 for uremia (BUN=20) and RR = 31 - consider inpatient CABP

What genetic dose changes need to be made with NNRTIs?

CYP2B6 poor metabolizers (PMs) are at greatest risk for higher dose-adjusted trough concentrations compared with NMs and IMs, and greater overall plasma efavirenz exposure, which puts these patients up to a 4.8-fold increased risk for adverse effects and treatment discontinuation (20-31). For these patients, there is a "moderate" recommendation to consider initiating efavirenz with a decreased dose of either 400 or 200 mg/day.

What characteristics do anaerobic bacteria have?

Can be Gram positive or negative Needs anaerobic environment to survive

What is Appendicitis?

Can be difficult to diagnose: - No clinical findings are unequivocal for diagnosis - Constellation of findings - Abdominal pain - Localized abdominal tenderness - Laboratory evidence of acute inflammation Current guidelines recommend development of local appendicitis pathway Antimicrobial tmt is recommended in all patients with diagnosis of appy

63 yo male admitted 2 weeks ago for partial colectomy He was doing well post-operatively until post-op day 3 he developed fever, increasing WBC and respiratory distress Chest XR showed right lower lobe infiltrate He was transferred to the ICU where he was intubated, a central venous catheter was placed and was started on piperacillin/tazobactam He initially improved but after 4 days his fever returned Daptomycin was added to cover possible catheter infection which has not been changed Repeat chest XR shows improvement, but his urine and blood cultures are growing yeast What are this patient's risk factors for invasive fungal infection? What are the most likely organisms? What empiric treatment do you recommend along with specific monitoring parameters?

Candida Risk factors: Surgery, recent Abx use Echinocandin if not resistant

What is Chlamydia?

Caused by C. trachomatis Frequently reported STI in the US 1.59 million cases in 2016 Serious sequelae PID, ectopic pregnancy and infertility

What is Gonorrhea?

Caused by N. gonorrhoeae 468,514 cases in 2016 Men: symptoms present to prompt treatment, but usually after they have spread the infection further Women: commonly asymptomatic, can lead to PID

What is Scabies?

Caused by Sarcoptes scabiei Pruritus is major symptom Sexually acquired in adults

What is Syphilis?

Caused by Treponema pallidum Primary - Ulcers or chancre at the site of infection Secondary - Skin rash, mucocutaneous lesions and lymphadenopathy Tertiary - Cardiac, gummatous lesions, tabes dorsalis and general paresis 1. Latent Early within the preceding year Late or syphilis of unknown duration 2. Neurosyphilis Early - cranial nerve dysfuntion, meningitis, stroke, AMS Late - tabes doralis and general paresis

What is Trichomoniasis?

Caused by Trichomonas vaginalis Most prevalent, non viral sexually transmitted infection in the US 3.7 million people Signs and symptoms Minimal - no symptoms (70 - 85%) Men - urethritis, epididymitis, prostatitis Women - diffuse, malodorous, yellow-green vaginal discharge

What is Toxoplasmosis (toxo)?

Caused by parasite Toxoplasma gondii Found in raw, undercooked meat and shellfish, and cat feces Primary infection caused by eating tissue cysts or oocytes Disease due to reactivation of latent tissue cysts AIDS defining illness Pregnant women also at risk Rare when CD4 count > 200 Highest incidence when CD4 count < 50 Clinical presentation in HIV patients: Encephalitis most common Fever, headache, confusion, motor weakness and seizures Diagnosis: brain biopsy

What is the Management of the Treatment-Experienced Patient Living with HIV?

Causes of virologic failure can be attributed to patient/adherence related factors, HIV-related factors, and ARV regimen-related factors.

What are the ADEs/monitoring of clindamycin?

Causes severe diarrhea *Toxicity: BBW - CDI (Colitis- C. diff), most likely to cause C. diff* Rash

What are the PO Cephalosporins?

Cefadroxil- Not really used, very similar to Cephalexin so people just use that Cephalexin Cefaclor Cefprozil Cefuroxime-axetil (IV AND PO, different salt formulation) Cefixime Cefpodoxime Cefdinir

What are the IV Cephalosporins?

Cefazolin Cefotetan Cefoxitin Cefuroxime (IV AND PO) Cefotaxime Ceftriaxone Ceftazidime Ceftazidime/avibactam Cefepime Ceftaroline Ceftolozane/tazobactam Cefiderocol

What are some Newer Antibiotics Approved Since 2011 Guidelines?

Ceftolozane/tazobactam (2014) Ceftazidime/avibactam (2015) *Meropenem/vaborbactam (2017)* *Plazomicin (2018)* Imipenem/cilastatin/relebactam (2019) *Cefiderocol (2019)*

Why do neonates get cefotaxime instead of ceftriaxone in their empiric therapy regimen? Hint: Does NOT have to do with spectrum of activity

Ceftriaxone is contraindicated in neonates because it displaces bilirubin from albumin binding sites, resulting in a higher free bilirubin serum concentration with subsequent accumulation of bilirubin in the tissues. It interacts with calcium-containing medications to form crystals that can precipitate in the lungs and kidneys, which has lead to fatalities,

What is the ADE/Monitoring for Cephalosporins?

Cephalosporins with N-methylthiotetrazole side chain (cefotetan and cefpodoxime) can inhibit vitamin K production and cause disulfiram-like reaction All others have similar ADE profile as rest of beta-lactams

What are the atypicals?

Chlamydia trachomatis Chlamydophila pneumoniae Mycoplasma pneumoniae Legionella pneumophila -Stains very poorly with Gram stain due to lipopolysaccharide content (although it is technically a Gram negative). You have to use special staining to see it so I have it reported under atypical

What is the Resistance in Pseudomonas aeruginosa?

Chromosomally mediated - DNA gyrase mutations (FQ) - Aminoglycoside modifying enzymes Decrease in porins Increased efflux pumps ESBLs New Delhi Metallo-beta-lactamases

What is Imipenem/Cilastatin/Relebactam?

Class: Beta-lactam/Beta-lactamase inhibitor combination MOA: imipenem binds to PBPs and relebactam prevents beta-lactamases from hydrolyzing imipenem Spectrum: Imipenem (*ESBL* Enterobacteriaceae, AmpC) Relebactam adds *KPC, CRE* and improved *Pseudomonas* *Doesn't improve activity against Acinetobacter* over imipenem by itself Absorption: IV only, so n/a Distribution: Imipenem - 24.3L, relebactam - 19 L Metabolism: Minimal Excretion: renal Monitoring/Adverse effects Renal function GI ADE Seizure RESTORE IMI I Phase III vs imipenem+colistin for HAP/VAP, cIAI, cUTI

What is Meropenem/Vaborbactam?

Class: Beta-lactam/Beta-lactamase inhibitor combination MOA: meropenem binds to PBPs and vaborbactam prevents beta-lactamases from hydrolyzing meropenem Spectrum: Meropenem *(ESBL Enterobacterales, AmpC)* Vaborbactam adds *KPC and CRE* *Doesn't improve activity against Pseudomonas or Acinetobacter* over meropenem by itself Absorption: IV only Distribution: ~ 20L for both components Metabolism: Meropenem: hydrolysis (minor) Vaborbactam: not metabolized Excretion: renally Monitoring/Adverse effects Renal function GI effects Headache Phlebitis, infusion site reactions Mild lethargy *TANGO 1* Phase III vs pip/tazo for cUTI/AP TANGO II Phase III for CRE

What is clindamycin?

Class: Lincosamide MOA: Bind to 50S subunit of the ribosome disrupting normal bacterial protein synthesis

What is Plazomicin?

Class: aminoglycoside MOA: inhibit bacterial protein synthesis by binding to 30s unit on ribosome Spectrum: Gram negatives: Enterobacterales (*ESBL* producing and CRE), *Pseudomonas aeruginosa* Absorption: IV only Distribution: 18 L Metabolism: not metabolized Excretion: renal Monitoring/Adverse effects Renal function GI ADE Neuromuscular blockade Ototoxicity *EPIC* Phase III vs meropenem for cUTI/AP CARE Pathogen directed trial vs colistin for CRE BSI or HAP/VAP

What is Delafloxacin?

Class: fluoroquinolone Chemically distinct from other FQs MOA: Inhibit DNA gyrase and topoisomerase IV Spectrum: similar to levofloxacin + *MRSA* Absorption: Lower F (59%) than other FQs Distribution: 35 - 48 L Metabolism: glucuronidation (low potential for drug interactions) Excretion: renal (50 -60%), feces unchanged (40 - 50%) Monitoring/Adverse effects - FQ BBW - GI - CNS effects TRIALS: PROCEED 1 and 2 Phase III vs vancomycin + aztreonam for ABSSSI *DEFINE CABP* *Phase III vs moxifloxacin/linezolid for CABP*

What is trimethoprim/sulfamethoxazole (TMP/SMX)?

Class: folate antagonist MOA: Inhibit folate biosynthesis - leading to inhibition of DNA synthesis SMX - competes with PABA, preventing formation of dihydrofolic acid TMP - binds to dihydrofolate reductase preventing the production of tetrahydrofolic acid

What is Fidaxomicin?

Class: macrolide (technically) MOA: inhibits RNA synthesis via binding to RNA polymerase Therapeutic uses: First line for CDI Adverse events/monitoring: GI effects

What is Nitrofurantoin?

Class: nitrofuran MOA: not well described Therapeutic uses: for lower urinary tract infections

What is Metronidazole?

Class: nitroimidazole MOA: Anaerobic bacteria only - interaction with metronidazole generates free radicals which results in inhibition of DNA synthesis and cell death

What is Lefamulin?

Class: pleuromutilin MOA: Lefamulin inhibits bacterial protein synthesis by interfering with the peptidyl transferase of the 50S ribosome Spectrum: Gram positive and atypical organisms associated with CABP (S. pneumo, H. influ, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae) Staph aureus *(+MRSA), VRE* MDR Neisseria gonorrhoeae Absorption: F = 25%, Cmax and AUC reduced with food Distribution: 86L Metabolism: metabolized by CYP450 (3A substrate and inhibitor) Excretion: 80% unchanged in feces, 13% unchanged in feces Monitoring/Adverse effects - Infusion site pain - Some GI effects, but less than compared with comparator LEAP 1 Phase III compared to moxifloxacin +/- linezolid for CABP LEAP 2 Phase III compared to moxifloxacin monotherapy for CABP

What is rifampin?

Class: rifamycin MOA: inhibits bacterial RNA synthesis by binding to RNA polymerase which prevents transcription

What is Cefiderocol?

Class: siderophore cephalosporin MOA: binds extracellular free ferric iron and transported into bacteria via a siderophore iron uptake, then binds to PBP3 Spectrum: Gram negatives: Enterobacterales (*ESBL* producing and CRE), *Pseudomonas aeruginosa, Acinetobacter baumannii* Absorption: IV only Distribution: 18L Metabolism: minimal Excretion: renal Monitoring/Adverse Events Well tolerated like other beta-lactams GI effects Injection site reaction Less CDI than imipenem APEKS-cUTI Phase II trial vs imipenem for cUTI

What are the Quinupristin/Dalfopristin?

Class: streptogramins MOA: Bind to 50S subunit preventing bacterial protein synthesis

What is Eravacycline?

Class: tetracycline MOA: binds to 30s subunit on ribosome, blocking protein synthesis Spectrum: S. aureus (*inc MRSA*), Strep, E. faecalis, E. faecium (*inc VRE*), N.gonorrhea, H.flu, M. catarrhalis, Enterobacteriaceace (*inc ESBL*), *Acinetobacter* and anaerobes Absorption: IV only Distribution: large, like other TCNs Metabolism: CYP 3A4 Excretion: 34% urine, 47% feces unchanged Monitoring/Adverse effects Infusion related reaction GI effects IGNITE 1 Phase III vs ertapenem for cIAI IGNITE 4 Phase III vs meropenem for cIAI

What is Omadacycline?

Class: tetracycline MOA: binds to 30s subunit on ribosome, blocking protein synthesis Spectrum: S.aureus (*MRSA*), S.pneumo (TCN‐resistant), other streptococci, Enterococci (*VRE*), H.flu, M.cat, anaerobes (C.diff), atypicals, E.coli, K.pneumo Absorption: 35% bioavailable (must give fasting) Distribution: large Vd like other TCNs Metabolism: none, P-gp substrate Excretion: 14% urine, 81% feces Monitoring/Adverse effects GI effects - no CDI reported Increased LFTs OASIS I and II Phase III vs linezolid for ABSSSI *OPTIC* *Phase III vs moxifloxacin for CABP*

What are some other ABX?

Clindamycin Rifampin TMP/SMX Nitrofurantoin Fosfomycin Metronidazole Quinupristin/dalfopristin Fidaxomicin Polymyxins

How is Bacterial Vaginosis diagnosed?

Clinical criteria or Gram stain

What is the CABP Hospital Admission scoring?

Clinical judgement PLUS PSI (Pneumonia Severity Index) is preferred over CURB-65 (conditionally) Confusion BUN (Uremia) RR BP The 2019 guidelines recommend PSI is recommended over the CURB-65 (conditionally), which means that you can use the CURB-65 score because it is easier

A patient presents to the hospital for back pain after slipping on ice. They are otherwise healthy, without any acute signs or symptoms of infection. Per standing ED orders, they have blood cultures drawn that are positive with 2/4 bottles (1 bottle in each set) for Coagulase negative Staphylococcus spp. What is the most appropriate assessment and treatment recommendation for this patient? A: This culture likely represents contamination and therefore does not require treatment at this time B: This culture likely represents a true infection and the patient should be started on vancomycin

CoNS= coagulas negative Staph and it grows on the skin, common contaminant A: This culture likely represents contamination and therefore does not require treatment at this time

What are Abscesses?

Collections of pus within the dermis & deeper skin tissues Painful, tender and fluctuant red nodules Often polymicrobial, containing regional skin flora or adjacent mucous membranes Usually S. aureus Treatment - Incision and drainage - Anti MRSA abx - SIRS and immunocompromised patients

What is the CDI Definition?

Combination of clinical and laboratory findings: - Presence of diarrhea - 3 or more unformed stools in 24 hours or less - Positive stool test for toxogenic C. difficile or its toxins - Colonoscopic or histopathologic findings of pseuomembranous colitis Repeat testing in same course is not recommended

What is VAP/HAP?

Common hospital - acquired infections (22%) High all cause mortality 20 - 50% for VAP Prolongs length of stay Prolongs length of mechanical ventilation HAP is associated with serious complications in ~ 50% of patients

What is the Clinical Presentation of PJI?

Communicating sinus tract Presence of purulence with unknown etiology surrounding prosthesis Acute onset of pain and inflammation Chronic pain unresolved by joint replacement

How are intra-abdominal infections classified to guide empiric treatment?

Community acquired - Mild to moderate severity - High risk Health care associated infection

What is a bacterial meningitis infection?

Community or healthcare associated The following discuss COMMUNITY bacterial meningitis Healthcare associated will be discussed with ventriculitis

What is the CABP outpatient empiric therapy algorithim?

Comorbidities? Yes- 1. Combo therapy with Amox/clav OR ceph AND macrolide OR doxy 2. Monotherapy with respiratory FQ No- Risk factors for MRSA OR Pseudomonas? No- Amoxicillin Or Doxycycline Or Macrolide Comorbidities include chronic heart, lung, liver or renal disease, DM, alcoholism, malignancy or asplenia Risk factors include prior respiratory isolation of MRSA or Pseudomonas aeruginosa or recent hospitalization AND receipt of IV antibiotics in the last 90 days if local pneumococcal resistance is < 25%

What is the CURB-65 Score?

Confusion, uremia (BUN > 20gm/dL), respiratory rate (≥30), low blood pressure (< 90 systolic or < 60 diastolic) , age > 65 years 5 possible points 0 - 1 (outpatient) 2 (consider inpatient) 3 or greater (inpatient) 4 -5 (consider ICU) Severe CABP = 1 major OR 3 or more minor criteria

What is the Anti-Enterococcal treatment?

Consider in selected immnosuppressed patients, particularly those with hepatic transplant Recommended if enterococcus is grown from cultures Recommended empirically HCA IAI - Post op infection - Those who have received a ceph or other enterococcus selecting antibiotic - Immunocompromised pts - Valvular heart disease or prosthetic intravascular materials Should empirically be targeted towards E. faecalis Does not need to be targeted against VRE unless high risk for VRE - Liver transplant with infection from hepatobiliary tree - Known colonizer of VRE

CSF cultures come back growing Pseuodomonas aeruginosa with the following susceptibilities Amikacin Intermediate Aztreonam Susceptible Cefepime Susceptible Ceftazidime Susceptible Ciprofloxacin Resistant Gentamicin Resistant Levofloxacin Resistant Meropenem Susceptible Piperacillin/tazo Susceptible Tobramycin Resistant How would you modify this patient's antibiotic therapy (definitive therapy)?

Continue Cefepime DC Vanco

P.D. remains stable postoperatively for 48 hours with no major improvement in symptoms Additional cultures are taken from an external abdominal drain and are pending The most recent intraoperative cultures return with multiple organisms and the following susceptibilities: Susceptible to everything Recommend a definitive therapeutic regimen.

Continue meropenem Add Vanco

What is Allergy Reconciliation?

Cornerstone of allergy delabeling strategy What allergies do you have? What was the reaction? Severity? Treatment? When did the reaction occur? What other similar agents have been tried since?

What are the Non-antimicrobial preventions?

Cranberry - potentially effective in ASB during pregnancy Topical estrogen - post menopausal women Probiotics - Lactobacillus spp in post menopausal women

What is Cross reactivity?

Cross reactivity with other beta-lactams is a clinical concern 1% cross reactivity of PCN to 1st generation cephalosporin with similar R1 side chains Negligible risk of cross reactivity with 2nd - 5th generations Recent, prospective studies suggest cross reactivity < 1% with carbapenems

What is Cryptococcus (Crypto)?

Cryptococcus neoformans - most common Cryptococcus gatti - Australia, PNW Ubiquitous in the environment Soil, pigeon/bird feces, decaying wood AIDS defining illness Highest incidence at CD4 < 100 Clinical presentation: CNS: Headache, lethargy, fever, altered mental status, nuchal rigidity, photophobia Pulmonary and skin: less common Diagnosis: culture, CSF microscopy (India ink stain) or by cryptococcal antigen (CrAg)

What is the definitive therapy for HAP/VAP?

Culture Confirmed MRSA? Yes- Vancomycin OR Linezolid No- Change to narrowest agent OR dc antibiotics if patient condition warrants Culture Confirmed Pseudomonas? Yes HAP-Continue antipseudomonal abx, Monotherapy appropriate (NOT AGs or polymyxins) Yes VAP- Continue antipseudomonal abx, High mortality risk/septic shock? Yes- continue combo No- monotherapy appropraite No HAP/VAP- Change to narrowest agent OR dc antibiotics if patient condition warrants

What is definitive therapy based off of?

Culture results

What is the Flucytosine Dosing Strategies?

Current place in therapy Combination with amB for cryptococcal meningitis 100 - 150 mg/kg/day Dose limiting toxicities and BBW

What disease states are considered UTIs?

Cystitis - lower tract infection of the BLADDER Pyelonephritis - upper tract infection of the KIDNEY Prostatitis - infection of the PROSTATE Asymptomatic bacteriuria (ASB) Catheter associated urinary tract infection (CA-UTI) - indwelling catheter use

What is Fosfomycin for a UTI?

Cystitis ONLY Minimal resistance and collateral damage Great activity against Enterobacterales, including ESBL producing organisms and Enterococcus spp High cost with variable insurance coverage Common side effects: diarrhea, nausea and headache

What are the Signs and Symptoms of a UTI?

Cystitis: dysuria, hematuria, increased frequency and super pubic pain Pyelonephritis: CVA tenderness, fevers, urgency, dysuria, chills, nausea and vomiting Prostatitis CA-UTI

Which of the following is a Gram positive cocci in clusters? A Bacillus cereus B Neisseria gonorrhoeae C Enterococcus facaelis D Staphylococcus aureus

D Staphylococcus aureus

What does an atypical organism look like on a Gram stain? A Blue/purple cocci or bacillus B Pink/red cocci or bacillus C Either blue/purple or pink/red depending on the organism D Translucent

D Translucent

Which of the following regimens would be appropriate for a 40 year old male with community acquired meningitis? A Meropenem and vancomycin B Ceftriaxone, ampicillin and gentamicin C Vancomycin, ceftriaxone and ampicillin D Vancomycin and ceftriaxone

D Vancomycin and ceftriaxone Add amp for >50 years old

R.G.'s WBC and body temperature have been improving. He has been working with physical therapy routinely in preparation for discharge in the next 24 hours. R.G.'s urine culture reveals the following: Which one of the following is best to recommend for R.G.? A. Tigecycline B. Colistin C. Cefepime D. Ciprofloxacin

D. Ciprofloxacin

An 86-year-old woman is admitted from a long-term care facility with a non-healing sacral decubitus ulcer that has not responded to levofloxacin. Which one of the following is mostly likely the cause of this patient's infection? A. Methicillin resistant S. epidermidis B. Vancomycin-resistant S. aureus C. Levofloxacin-resistant S. pneumoniae D. Methicillin-resistant S. aureus

D. Methicillin-resistant S. aureus

Which of the following patients is IE prophylaxis indicated in prior to their dental appointment? A: 18 year old with diabetes type 1 having braces tightened B: 27 year old healthy patient with no significant PMH having a dental cleaning C: 56 year old with hypertension having routine dental radiographs completed D: 86 year old with prosthetic valve in the mitral position having a root canal done

D: 86 year old with prosthetic valve in the mitral position having a root canal done

Which of the following is a recommended empiric treatment regimen for mild-moderate community acquired intra-abdominal infection? A: Meropenem B: Cefepime C: Piperacillin/tazo + gentamicin D: Cefoxitin

D: Cefoxitin For mild/moderate for adequate activity against certain pathogens, enteric gram +/- or anaerobes (second gen ceph) Other answers are for pseudomonas coverage which we don't need for community Cefepime doesn't have anaerobic coverage so it can't be used monotherapy for this

Which of the following bacteria are commonly implicated in catheter associated urinary tract infections (CA-UTI)? A: Staphylococcus aureus B: Pseudomonas aeruginosa C: Acinetobacter baumannii D: Corynebacterium urelyticum

D: Corynebacterium urelyticum

Which is a criteria for double Pseudomonal activity in patients with VAP? A: Oral antibiotic use within 90 days B: 5% resistance to monotherapy C: Diabetes D: Cystic fibrosis

D: Cystic fibrosis

A 37 year old patient with history of IVDU was started on vancomycin and gentamicin for suspected native valve IE. Today, the patient's blood cultures are growing Methicillin susceptible Staphylococcus aureus in all bottles of 2 sets. Which of the following is the most appropriate definitive therapy for this patient A: Add rifampin to current therapy of vancomycin and gentamicin B: Discontinue gentamicin, continue vancomycin C: Discontinue vancomycin and gentamicin. Start daptomycin D: Discontinue vancomycin and gentamicin. Start nafcillin

D: Discontinue vancomycin and gentamicin. Start nafcillin

The toxigenic strain of C. diff (BI/NAP1/027) is most commonly associated with which antibiotic? A: Amox/clav and Amp/sulb B: Clindamcyin C: Vancomycin D: Levofloxacin

D: Levofloxacin Because now it's used for CAP in guidelines

A patient is diagnosed with uncomplicated cystitis. The local urinary antibiogram shows resistance rates to the most common urinary pathogens: ciprofloxacin 30% resistant, sulfamethoxazole/trimethoprim 30% resistant. Which of the following is the most appropriate empiric treatment recommendation for this patient? A: Sulfamethoxazole/trimethoprim B: Ampicillin C: Ciprofloxacin D: Nitrofurantoin

D: Nitrofurantoin

A young woman is seen by her PCP for a gynecological exam. She is sexually active and otherwise healthy. All other physical exam findings were within normal limits. A routine urinalysis was performed and the dipstick came back positive for bacteria. The physician asks for your recommendation. The local urinary antibiogram shows a 10% resistance rate for the most common urinary pathogens to both the fluoroquinolones and sulfamethoxazole/trimethoprim. Which of the following is the most appropriate recommendation for this patient? A: Nitrofurantoin 100 mg PO BID x 5 days B: Sulfamethoxazole/trimethoprim 160/800 PO BID x 3 days C: Ciprofloxacin 250 mg PO BID x 3 days D: No treatment indicated

D: No treatment indicated Asymptomatic

A 25 year old female patient presents to the clinic with dysuria, fever, chills and flank pain. She is diagnosed with a urinary tract infection. Which of the following is the most appropriate classification of her UTI? A: Cystitis B: Asymptomatic bacteriuria C: Catheter associated urinary tract infection D: Pyelonephritis

D: Pyelonephritis

When is it best to start treatment for a new patient infected with HIV? A: CD4<200 B: CD4<350 C: CD4<500 D: Regardless of any CD4 cell count

D: Regardless of any CD4 cell count

A patient is started on ampicillin and gentamicin for native valve Enterococcal IE. Which of the following would be the most relevant monitoring parameter to assess the efficacy of the antibiotic regimen? A: CPK B: Renal function C: Gentamicin trough D: Repeat blood cultures

D: Repeat blood cultures

A 53 year-old male patient who is newly diagnosed with HIV infection presents to the clinic with oropharyngeal candidiasis. His CD4 count is 155 cells/mm3, and his viral load is 120,000 copies/mL. He denies any medication allergies. While awaiting baseline genotypic resistance testing results, which is the most appropriate NEXT step in his management? A: Start voriconazole B: Start isavuconazole C: Start fluconazole, trimethoprim and azithromycin D: Start fluconazole and trimethoprim/sulfa

D: Start fluconazole and trimethoprim/sulfa

Which of the following is a Gram positive bacteria that is likely to be an implicating organism in a community acquired high risk intra-abdominal infection? A: Proteus spp B: Enterobacter spp C: Bacteroides spp D: Streptococcus spp

D: Streptococcus spp

Which of the following is the treatment of choice for necrotizing fasciitis? A: Vancomycin B: Piperacillin/tazobactam C: Local wound care D: Surgical debridement of necrotic tissue

D: Surgical debridement of necrotic tissue

Which is the causative organism in Syphilis infection? A: C. trachomatis B: N. gonorrhea C: T. vaginalis D: T. pallidum

D: T. pallidum A: C. trachomatis- chlamydia B: N. gonorrhea- gonorrhea C: T. vaginalis- trich

Which of the following is an appropriate empiric regimen for a patient with suspected ventriculitis? A: Ampicillin, cefotaxime and gentamicin B: Vancomycin, ceftriaxone and ampicillin C: Vancomycin and ceftriaxone D: Vancomycin and cefepime

D: Vancomycin and cefepime Gram positive: Vancomycin PLUS Gram negative rods for Pseudomonas with good CNS penetration: Cefepime, Ceftazidime, Meropenem

K.K.'s surgery is uneventful and no perforation or peritoneal involvement is observed. Post-operatively, she is noticed to have a new rash appearing on her upper chest. She has been scheduled to receive two more doses of antibiotics What is your recommendation for this patient?

DC Antibiotics, not indicated anymore

What is Necrotizing Fasciitis?

Deep infections of the fascia and/or muscle compartments Can lead to major tissue destruction and even death Usually related to trauma Can often be confused with cellulitis Cellulitis will respond to antimicrobial treatment Necrotizing fasciitis requires surgical intervention Will have systemic toxicity

What is a C diff Recurrence?

Definition: relapse of infection with original strain or re-infection with a new strain 10 -30 % of patients with CDI experience at least 1 additional episode Risk factors for recurrence Age > 65 years Antimicrobials during or after initial treatment Fluoroquinolone use Current, recurrence

1-3, B-D-Glucan antigen + BAL + Aspergillus fumigatus How would you modify current antimicrobial regimen (definitive therapy) ? Make sure to mention monitoring parameters for which ever agent(s) you choose The patient continued to deteriorate despite appropriate therapy and ended up passing away Discuss what are some potential reasons for therapy failure?

Definitive therapy: voriconazole Trough: 1-5.5 mg/L

What are the CMV Treatment Options?

Dependent on location and severity of lesion Preferred, severe (immediate sight-threatening lesions): need intravitreal injections + systemic therapy Intravitral injections: ganciclovir or foscarnet Systemic therapy: valganciclovir Preferred, not immediate sight-threatening (smaller peripheral lesions) Systemic therapy only - valganciclovir Duration of therapy: until CD4 count > 100 for ≥ 3 - 6 months

What is the definitive therapy for a brain/epidural Abscess?

Depends on culture and sensitivity Need to select antibiotic that will treat the infection site Treatment is 4 - 6 weeks (longer without surgery)

What is the Duration of Therapy of an IE treatment?

Depends on valve type AND infecting organism Shorter courses (~2 weeks) can be used in uncomplicated cases with susceptible organisms in native valves Longer courses (≥ 6 weeks) are usually for prosthetic valves and/or more resistant organisms

*What are Facility Specific Treatment Recommendations?*

Development of clinical practice guidelines, algorithms and order sets based on local epidemiology Pros: Standardizes practices based on what is seen locally Antibiotic selection and duration Common infections Community-acquired pneumonia Urinary tract infection Intra-abdominal infection Skin and soft tissue infection Surgical prophylaxis Cons: Most useful if the ASP has a reliable way to identify patients with specific syndromes Regularly need to be evaluated and updated with local resistance data Needs interventions to maintain guideline adherence over time

What are the Adjunctive Treatments for bacterial meningitis?

Dexamethasone 0.15 mg/kg q 6 hours for 2 - 4 days should be given 10 - 20 min prior or with first dose of abx Infants/Children: Reduced hearing impairment in patients with *H. influenzae type B* Adults: Reduces unfavorable outcomes and death in patients with *S. pneumo*

How is Aspergillosis diagnosed?

Diagnosis 1-3 Beta-D-glucan Serum BAL CT scan (usually chest)

How is Mucormycosis (zygomycosis) diagnosed and treated?

Diagnosis: Histopathologic documentation Treatment: AmB Posaconazole Isavuconazole

What are the Clinical Challenges surrounding IE?

Difficult to diagnose Delayed therapy = poorer outcomes Increased mortality and embolic events Optimal antibiotic therapy varies based on patient specific factors

How is PID diagnosed?

Difficult to diagnosis Combination of historical, physical and laboratory findings needed Need low threshold for treatment Presumptive PID in sexually active young women with one or more Cervical motion tenderness Uterine tenderness Adnexal tenderness

What is Kirby Bauer?

Disc diffusion 1. Plated bacteria with different antibiotics at a set concentration 2. Creates zones of inhibition 3. Measure zones of inhibition- the larger the zone, the greater effect the antibiotic had

What are the Itraconazole Dosing Strategies?

Doses vary based on indication Ie Aspergillosis 200 mg TID x 3 days then 200 mg BID Variable absorption with different formulations Bioavailability affected by food and changes in gastric pH Capsules - need stomach acid, therefore no PPIs or H2RA, also need a full meal Solution - needs empty stomach

What ONLY covers MSSA?

Doxycycline Minocycline Tetracycline SMX/TMP

What are the Tetracyclines for CABP?

Doxycycline 100 mg twice daily

What is the Aspergillosis prophylaxis?

During prolonged neutropenia, high risk patients Posaconazole, voriconazole, micafungin

How to decide between different INSTIs for treatment-naïve patients?

EVG- not approved for ART- experienced patients Weight gain for all of them for ART-naive peoples HIV/RNA >500,000 units/mL do not use DTG/3TC HLA-B5701 do not use ABC-containing regimens Avoid NNRTIs and DTG/3TC *CKD and Osteoporosis = Avoid TDF* Psychiatric illnesses= Avoid EFV and RPV regimens High cardiac risk= certain ART regimens are more favorable lipid profiles

What are the classifications of PJI?

Early onset: < 3 months Delayed onset: 3 - 24 months Late onset: >1-2 years

What do the PrEP Trials Demonstrate?

Efficacy in Different Populations

What is Infective Endocarditis (IE)?

Endocarditis described by William Osler in 1885 Infection of the endocardial surface of the heart Most commonly affects the mitral valve, then aortic, tricuspid and pulmonic valves Can also occur within septal defects or on mural endocardium Most commonly caused by bacteria, but can also be caused by fungi or viruses

*What is Prospective Audit and Feedback?*

Engagement of the prescriber after an antibiotic is prescribed Pros: Increased visibility of ASP and builds collegial relationships More clinical data available for recommendations, enhancing uptake by prescribers Greater flexibility in timing of recommendations Provides educational benefit to clinicians Prescriber autonomy maintained Can address de-escalation of antibiotics and duration of therapy Cons: Compliance voluntary Typically labor-intensive Success depends on delivery method of feedback to prescribers Prescribers may be reluctant to change therapy if patient is doing well Identification of interventions may require information technology support and/or purchase of computerized surveillance systems May take longer to achieve reductions in targeted antibiotic use

What is the Community Acquired Mild to Moderate treatment for intra-abdominal infections?

Enteric Gram - negative and facultative bacilli & enteric Gram - positive (Strept) Obligate anaerobic bacilli Ampicillin/sulbactam is not recommended (E. coli) Cefotetan & clindamycin are not recommended (B. fragilis) Aminoglycosides (AG) are not recommended No enterococcal or candida activity needed For mild to moderate severity, perforated or abscessed appendicitis 1. Single agent Cefoxitin, ertapenem, moxifloxacin 2. Combination Cefazolin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin or levofloxacin PLUS Metronidazole

What are some ways of Preventing Spread of Resistance?

Environmental factors Strict hand hygiene Stringent cleaning/disinfecting Antimicrobial stewardship

What are Beta- Lactamases?

Enzymes that can hydrolyze beta-lactams -Vary based on type of enzyme ESBL (*TEM, SHV, CTX-M*) Carbapenemases (*KPC*, IMI, *VIM*, IMP, NDM, OXA) AmpC (AmpC, CMY, FOX, DHA, ACC)

What is the Presentation of IE?

Evaluation should always include valve status and underlying comorbidities 1. Non - specific signs and symptoms Fever, chills, nausea, vomiting, fatigue & malaise 2. Heart murmur Present in 85% of cases, may be hard to detect in ED Right-sided, <50% have murmurs detected on admission 3. Skin manifestations (18 - 50%) Osler's nodules (10 - 23%) Splinter hemorrhages (15%) Petechiae (20 - 40%) Janeway lesions (< 10%)

When to Start Antiretrovirals (ARVs)?

Everyone with HIV to reduce mortality, morbidity, and to prevent transmission of HIV to others Antiretroviral Therapy to Prevent Sexual Transmission of HIV (Tasp): *<200 copies/mL* prevents transmission to others through transmission to partners Undetectable=Untransmittable

What are some Newer Agents Since 2010 Guidelines?

FDA approved for complicated intra-abdominal infections (cIAI) Ceftolozane/tazobactam (2014) Ceftazidime/avibactam (2015) *Eravacycline (Aug 2018)* *Imipenem/cilastatin/relebactam (July 2019)* Place in therapy?

A treatment naive pt with CD4 count 250 and VL 150,000 copies can use TAF/FTC/rilpivirine T/F

False

Ca and Fe containing antiacids can be safely co-administered simultaneously with dolutegravir T/F

False

Ceftriaxone is an oral cephalosporin with activity against many anaerobes. True/False

False

LP is a 25 year old man with meningitis. He was started on vancomycin and ceftriaxone. His culture results come back positive for Streptococcus pneumoniae. Dexamethasone an appropriate adjunct treatment to add at this point? True/False

False

True or false: Urine is sterile

False

True or false. Mild diabetic foot infections tend to be polymicrobial.

False- monomicrobial with strep or staph Severe is polymicrobial usually with staph, strep, anaerobes, pseudomonas

True or false: Trichomoniasis can be effectively treated with metronidazole gel

False: it is used for BV Need more than the topical effect

What is HIV: A Retrovirus?

Family: Retroviridae Pathogenic human retroviruses lenti retroviruses (HIV-1, HIV-2) onc retroviruses (HTLV-I, -II) *HIV-1: most common virus, more virulent* HIV-2: originally restricted to West Africa most commonly related to SIV vs. HIV-1

How does PCP present?

Fever, dyspnea, non or mildly productive cough, chest discomfort Mild - moderate - hypoxia with PaO2 > 70 mmHg Severe - hypoxia with PaO2 < 70 mmHg Diagnosis: bronchoscopy with lavage

How are intra-abdominal infections initially treated?

Fluid resuscitation Requirement of emergent intervention

CC: SOB, fever, chills, rigors, night sweats and stabbing left chest pain EP is a 31 yo male, 75 kg, NKA, ht 70 in, Scr 0.8 Had positive blood cultures, came into hospital TEE: moderate mitral regurgitation with vegetation on the atrium side and vegetations on aortic valve PE: good dentition, no periodontal disease, has not been to the dentist in the last year. No skin manifestations Imaging: CT confirms splenic infarctions DX: Infective Endocarditis, Native Valve What are the most likely organisms causing this patient's infection? Recommend empiric therapy for this patient Be specific with doses and monitoring Recommend a definitive treatment plan Antibiotic Duration of therapy (not an objective per se, but might as well add for completeness sake) Monitoring parameters

Gentamicin with Vancomycin Definitive therapy: Gram + Strep viridians Need synergy because immunocompromised Monitor for troughs

How do we Monitor Antiretroviral Therapy?

Goal of Treatment with ART: undetectable VL (i.e. VL<20 copies/mL) by 24 weeks

What are the therapeutic uses for AGs?

Gram negatives - Used as second agent in combination therapy when multi drug resistance is suspected Gram positive synergy - Enterococci (gentamicin only)

What are two anaerobes?

Gram positive = Peptostreptococci Gram negative = Bacteroidies fragilis

What are the therapeutic uses for Quinupristin/Dalfopristin?

Gram positive organisms such as MRSA or E. faecium if no or limited alternatives

What is the Empiric Treatment for healthcare associated ventriculitis and meningitis?

Gram positive: Vancomycin PLUS Gram negative rods for Pseudomonas with good CNS penetration: Cefepime, Ceftazidime, Meropenem

In-class Case 1: You are on rotation and you have a patient with a UTI started on ceftriaxone empirically. When reviewing the culture data, you see a Gram stain for a Gram negative rod, Aeromonas spp, in the urine that is awaiting final susceptibilities. Since the patient was symptomatic with a UTI, the team wants to treat this bacteria. The patient is in stable condition on the general medical floor. Neither you nor your preceptor have heard of this bacteria before and wonder if ceftriaxone can be used to treat this infection Using your Sanford Guide, please find the susceptibility pattern of this bacteria Were you able to find the answer? If so, where, specifically in the Sanford Guide? What is the answer? Can you use ceftriaxone?

Green + sign so yes! Page 79

What are the Probiotics?

Gut flora restoration is crucial Some evidence in prevention of Antibiotic Associated Diarrhea SHEA-IDSA statement: There are insufficient data at this time to recommend administration of probiotics for primary prevention of CDI outside clinical trials

What are the pros/cons to the different HIV tests?

HIV Tests for Screening and Diagnosis HIV tests are very accurate, but no test can detect the virus immediately after infection. How soon a test can detect infection depends upon different factors, including the type of test being used. There are three types of HIV diagnostic tests: nucleic acid tests (NAT), antigen/antibody tests, and antibody tests. 1. NATs look for the actual virus in the blood. This test is very expensive and is not routinely used for HIV screening unless the person recently had a high-risk exposure or a possible exposure with early symptoms of HIV infection. 2. Antigen/antibody tests look for both HIV antibodies and antigens. Antigens are foreign substances that cause your immune system to activate. If you're infected with HIV, an antigen called p24 is produced even before antibodies develop. Tests that detect both antigen and antibodies are recommended for testing done in labs and are now common in the United States. There is also a rapid antigen/antibody test available. 3. Antibody tests detect the presence of antibodies, proteins that a person's body makes against HIV, not HIV itself. Most rapid tests and home tests are antibody tests. An initial HIV test usually will either be an antigen/antibody test or an antibody test. If the initial HIV test is a rapid test and it is positive, the individual will be sent to a health care provider to get follow-up testing. If the initial HIV test is a laboratory test and it is positive, the laboratory will usually conduct follow-up testing on the same blood sample as the initial test. Although HIV tests are generally very accurate, follow-up testing allows the health care provider to be sure the diagnosis is right. -most updated July 2020

What is Infection Control for C diff infections?

Hand hygiene with SOAP and water: not antimicrobial gels Gown and glove Use bleach solution for cleaning Patient and family education - Wash hands before eating

P.D. is a 44-year-old trauma patient admitted to the SICU after multiple stab wounds. He has been in the ICU for 6 days since his admission and has had two subsequent surgeries for multiple visceral repairs, including lung and peritoneal punctures On hospital day 7, P.D. begins to spike a fever of 39 C with increasing abdominal tenderness and distention Other vital signs and chemistries remain within high-normal ranges P.D. developed a minor diffuse rash postoperatively, possibly caused by pre-operative cefazolin. Exploratory abdominal surgery reveals a small unrepaired leak in the colon and diffuse peritonitis. Intraoperative cultures are obtained and pending. Classify this patient's infection What are the most likely organisms? Recommend an empiric antibiotic regimen for this patient

Healthcare associated intra-abdominal infection Resistant GNR & anaerobes mainly MRSA coverage needed? Maybe VRE? Only if high risk (liver tx with infection or known colonizer) Pip/Tazo or Meropenem

What is the empiric therapy for HAP?

High Mortality Risk OR IV antibiotics in last 90 days? Yes- Combo therapy for Pseudomonas PLUS AntiMRSA agent (3 antibiotics total) 2 antipseudomonal agents: Pick 1 Beta-lactam PLUS Pick 1 Non-Beta-lactam AND AntiMRSA agent No- Monotherapy with antipseudomonal beta-lactam, add antiMRSA agent if MRSA risk

What is the Posaconazole TDM?

Higher concentrations are associated with higher response rates Prophylaxis > 0.7 mg/L (trough) Salvage treatment > 1.25 mg/L (trough) Draw trough at 7 days Indicated in patients lacking response, GI dysfunction, PPI therapy or DDI

What is the IE Definitive Therapy for a patient with a Strept spp (VGS and S. gallolyticus) infection?

Highly PCN susceptible (MIC ≤ 0.12 mcg/mL) Native or prosthetic valve: 3 options 1. Penicillin +/- gentamicin 2. Ceftriaxone +/- gentamicin 3. Vancomycin

What is SMX/TMP for a UTI?

Highly effective Only can use empirically where resistance rates are < 20 % Major side effects: rash, urticaria, nausea/vomiting and hematologic side effects

What is Histoplasmosis?

Histoplasma capsulatum Mid/southeastern US, Central and South America Found in decaying bird (starlings and blackbirds) and bat guano Clinical manifestations: Self limited, acute, influenza-like illness Can progress

How can we use PRECISION MEDICINE to Guide ABACAVIR Therapy?

Hypersensitivity (HSR) affects ~6% of patients and can be life-threatening with repeated dosing At least two of following symptoms: fever, rash, GI symptoms (nausea, vomiting, abdominal pain), fatigue, cough + dyspnea Frequency of the HLA-B*5701 allele African/Asian (2-3%) European (6-7%) Clinical studies (PREDICT-1) FDA recommends screening for all pts prior to use

What is the Prophylaxis for IE?

IE is more likely to occur with ADL rather than a single medical or dental procedure - Teeth brushing and chewing food Benefits do not out weigh costs - Resistance, side effects etc Consistently good oral hygiene is best Only 4 patient groups are considered 1. Patients with prosthetic valves 2. Patients with previous IE 3. CHD 4. Cardiac transplant with cardiac valvuopathy Patients with mitral valve prolapse with or without mitral regurg and patients with bicuspid aortic valves no longer require ppx

What are the Posaconazole Dosing Strategies?

IV - 300 mg q 12 hr x 2 doses then 300 mg daily PO tablet - 300 mg q 12 x 2 doses then 300 mg daily PO suspension - 200 mg TID NOT interchangeable, all orders must specify the dosage form, strength and frequency

For Exam

If given a blood culture, determine whether it is a contaminant or a pathogen Make sure to know empiric therapy for native and prosthetic valve IE based on risk factors Be able to select appropriate definitive therapy based on blood cultures results Recognize which patients require IE ppx

What are the Diagnostic Tests for osteomyelitis?

Imaging: MRI or CT scan Wound culture - Superficial wound or sinus tract sample Blood cultures - More helpful if positive, can reduce the need for bone cultures Bone biopsy and histopathology - Gram stain, culture and sensitivity testing

How common are OIs?

In general, decreased with time Increase with HIV infection time as CD4 count decreases

What is the purpose of clindamycin for necrotizing fasciitis?

In in vitro and animal models, clindamycin decreases toxin production in necrotizing fasciitis caused by invasive group A streptococci. *Shuts down toxin production by inhibiting proteins and shut down the ribosome*

What is Antimicrobial Resistance?

Inactivity of an antibiotic against a microorganism to which it previously had activity Consequence of the use of antimicrobials "Antibiotics are victims of their own success" - anonymous

What is the Epidemiology of IE?

Incidence of 1.5 to 11.6 cases/100, 000 worldwide Most patients have an identifiable predisposing cardiac abnormality or risk factor >50% of cases in US and Europe are in patients > 60 years old

Why is antimicrobial resistance bad?

Increases mortality Increases morbidity Prolongs hospitalization Increased cost Drug, doctor visits and healthcare use Economic costs $20 billion direct $35 billion for loss of productivity

What is the Prevalence of Comorbidities in HIV-infected pts versus HIV un-infected pts?

Increasing Prevalence of Comorbidities Higher in HIV-infected pts versus HIV un-infected pts Increase in NCDs= non-communicable diseases included cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies and start co-medication for these diseases

What is Antifungal Therapy?

Indicated if Candida grown from cultures Fluconazole is recommended for C. albicans If fluconazole resistant, then can use an echinocandin Empiric tmt with echinocandin is recommended in critically ill patients

K.K. is 12-year-old girl being examined in the emergency room for possible appendicitis PMH: no significant medical history NKA Upon examination and radiologic reports, K.K. is diagnosed with appendicitis with a suspicion of perforation and is scheduled for surgical resection. Classify this patient's infection What are the most likely organisms? Recommend an empiric antibiotic regimen for this patient

Infection: Mild/moderate community acquired Bacteria: Strep, anaerobes Empiric: cefoxitin

What are the therapeutic uses of metronidazole?

Infections caused by anaerobic bacteria such as intra-abdominal infections, trichomoniasis and protozoal infections

What are the therapeutic uses of Oxazolidinones?

Infections caused by resistant Gram positive organisms such as MRSA and VRE PNA and ABSSTIs

What is the DFI (Diabetic foot infection) Presentation?

Infections tend to be more extensive than they appear Pain sensations are diminished - May complain of swelling/edema Clinical signs and symptoms may not be present Lesion vary in size and clinical features

What are the therapeutic uses of macrolides?

Infections with atypical organisms such as lower respiratory tract infections like CAP, chlamydia, atypical mycobacterial infections, H. pylori

*Who are the Members of the ASP?*

Infectious Diseases (ID) physician- leader overall outcomes Clinical pharmacist with ID training- co-leader day-to-day, reports, clinical outcomes Hospital epidemiologist- identify MDROs, surveillance, monitor and reports MDROs Infection control/prevention- hand washing Microbiologist- diagnostic stewardship, culture sensitivity reports, develop antibiograms IT specialist

What is the pathogenesis of encephalitis?

Inflammation of brain tissue itself with clinical evidence of neurologic dysfunction Mainly caused by viruses - HSV, west nile virus, enterovirus

What is an antibiogram?

Institution or region SPECIFIC Cannot be applied to other settings or parts for the country Allows for assessment of TRENDS in resistance patterns Used for EMPIRIC antibiotic selection Use culture specific data once available Helps to assess changes of susceptibility over time Numbers are the % susceptible so higher is better

What are the One Pill-Once Daily ART Combinations in US (2020)?

Integrase Strand Transfer Inhibitors (INSTIs) -Stribild® (TDF/emtricitabine/elvitegravir/cobicistat) -Genvoya® (TAF/emtricitabine/elvitegravir/cobicistat) -Triumeq® (abacavir/lamivudine/dolutegravir) -Dovato® (lamivudine/dolutegravir) -Biktarvy® (TAF/emtricitabine/bictegravir)

What are the DFI Treatment: Questions to Consider?

Is there clinical evidence of infection? For infected wounds: Is there a high risk for MRSA? Has patient received antibiotics in the last month? Are there risk factors for Pseudomonas? What is the infection severity status?

What is the Isavuconazole Dosing Strategies?

Isavuconazonium sulfate 186 mg = 100 mg isavuconazole IV and PO available 372 mg isavuconazonium every 8 hours for 6 doses, then 372 mg daily thereafter TDM is not necessary

How would the previous graph look if we extended the infusion time to 4 hours (previously it was over 30 min) and still administer the antibiotic every 6 hours? In what circumstances would this be beneficial clinically? AUC over time

It increases the time over the MIC to increase the infusion time

What is the trend in syphilis in newborns?

It is accelerating

What is the trend in syphilis in men?

It is accelerating, particularly among gay and bisexual men

Day 3: Urine cultures come back with the following sensitivity information Amikacin: R Aztreonam R Cefepime R Ceftazidime/avibactam I Ceftolozane/tazobactam I Ciprofloxacin R Gentamicin R Imipenem/cilastatin S Levofloxacin R Meropenem S Piperacillin/tazobactam I Tobramycin R How would you modify therapy at this point? (Definitive therapy)

Keep Meropenem

CC: Severe headache and subjective fevers HPI: a 52 year old male presents to the ED with worsening headache and neck pain for 1 day duration. Low grade fevers for past 2 days along with 2 episodes of nausea and associated vomiting. PMH: COPD, HTN, hyperlipidemia Surgical Hx: none FH: mother has HTN and DM SH: former tobacco use 30 pack years NKA Home medications: Fluticasone propionate/salmeterol xinafoate 250 mcg/50 mcg, one inh BID Albuterol MDI, one inh q 4 hr PRN SOB Lisinopril 20 mg PO daily Atorvastatin 20 mg PO daily Vitals: temp 102.1 F, HR 77, RR 24, BP 160/80, ht 63 in, wt 56.4 kg General: lethargic, dizzy, moderate distress HEENT: normal, poor dentition Pulm: diminished breath sounds, crackles bilaterally CV: normal Abdominal: normal GU: deferred Neuro: lethargic, oriented to person and place, + Brudzinski's sign, + Kernig's sign Extremities: petechial lesions on lower and upper extremities Labs: abnormal: Scr 1.7 mg/dL, glucose 168 mg/dL All others normal: WBC 8 X 10^3 cells/mm^3 CT Head: diffuse hypodensity, possibly from previous stroke Cultures: Blood, LP/CSF - pending Assessment: What is a likely sign or symptom of bacterial meningitis for this patient? What is (are) the most likely bacteria responsible for this patient's CNS infection? Plan: Select an appropriate empiric regimen for this patient Make sure to include appropriate monitoring parameters

Kernig's sign- inability to bend knee when hips are flexed Brudzinski's sign- Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed Because of age: could be S. pneumoniae, Neisseria meningitidis, Listeria For 50+ Bacteria: Strep pneumoniae, Neisseria meningitidis, L. monocytogenes, aerobic gram - bacilli Vancomycin + Ampicillin + third gen cephalosporin

What are the gram negative bacilli?

Klebsiella spp. Escherichia coli Acinetobacter spp. Pseudomonas aeruginosa Haemophilus influenzae

What are the Mechanisms of Antiretroviral-Associated Drug Interactions?

Knowledge of these interacting potentials will help to predict DDIs with other medications if you know how they are metabolized Most drug-drug interactions are the result of CYP inhibition and induction PIs are OATP inhibitors DTG and BIC are P-gp substrates Bictegravir is a substrate for CYP3A4 and UGT1A1 and similar to DTG also is an inhibitor of renal transporters OCT2 and MATE1 Cobicistat is an inhibitor of CYP3A4 and a weak inhibitor of CYP2D6; in addition, it inhibits ATP-dependent transporters BCRP and P-glycoprotein and the organic anion transporting polypeptides OAT1B1 and OAT1B3. Potential exists for multiple drug interactions. Ritonavir also appears to induce CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6 as well as other enzymes, including glucuronosyl transferase

What characteristics do atypical bacteria have?

Lacks a cell wall Does not Gram stain

What is the Duration of therapy for AOM?

Less than 2 years of age- 10 days Children > 2 years of age- 5 to 7 days Azithromycin (any age)- 5 days Ceftriaxone IM (any age)- 1-3 doses, depending on response

What ONLY covers Streptococcus spp?

Levofloxacin (4) Moxifloxacin (4) Gemifloxacin (4) 4- Levofloxacin, moxifloxacin and gemifloxacin DO NOT have activity against Groups A,B,C,F,or G, or S. anginosus group

What are the gram positive bacilli? (1)

Listeria monocytogenes

What is the Yeast TTP?

Longer than bacteria C. albicans 58.4 ± 18.2 hours C. tropicalis 50.6 ± 13.9 hours C. parapsilosis 71.3 ± 26.9 hours C. glabrata 90.7 ± 36.5 hours

Which of the following displays the highest rate of susceptibility for the bacteria Staphylococcus aureus in the antibiogram: a. clindamycin b. oxacillin c. linezolid d. trimethoprim/sulfamethoxazole

Looking for biggest number/highest percentage c. linezolid

What are the Predictors of Virologic Success with ARV Therapy?

Low baseline HIV viral load High potency Tolerability Convenience Excellent Adherence

What is the synergy used for in IE treatment?

Low dose gentamicin is often used for gram positive synergy in GP IE Usually 1 mg/kg q 8hr (dose adjusted based on renal function) Once daily is supported only in Streptococcal IE (3 mg/kg/day) No longer recommended for NV Staph aureus IE

What is Fosfomycin?

MOA: Prevents production of precursors of peptidoglycan Therapeutic uses: PO for urinary tract infections only Adverse events/monitoring: GI effects

What is Clarithromycin?

MOA: binds to 50s subunit, inhibiting bacterial protein synthesis OI clinical uses: MAC ppx (preferred, monotherapy) MAC treatment (primary, need another agent) *More drug interactions than azithromycin* Adverse effects: Hepatotoxicity Ototoxicity (with high doses or prolonged use) Headache *Nausea, vomiting, abdominal cramps, diarrhea* Rash *QTc prolongation* Dysgeusia

What is Azithromycin?

MOA: binds to 50s subunit, inhibiting bacterial protein synthesis OI clinical uses: MAC ppx (preferred, monotherapy) MAC treatment (primary, need another agent) Adverse effects: *Nausea, vomiting, diarrhea* Hepatotoxicity Ototoxicity (with prolonged use) Rash, urticaria, pruritus Abdominal pain *torsades de pointes (risk is greatest in patients with underlying QTc prolongation)*

What is Amphotericin B?

MOA: binds to sterols in the cell membrane, leading to cell death OI clinical uses: Cryptococcal meningitis tmt (primary induction therapy + flucytosine) Candidiasis tmt (alternate) *BBW:* Amphotericin B should be used primarily for treating patients with life threatening fungal infections, and NOT for noninvasive. Exercise CAUTION to prevent overdosage, which can result in potentially fatal cardiac or cardiopulmonary arrest.

What is Flucytosine?

MOA: converted to 5FU, interferes with nucleic acid and protein synthesis OI clinical uses: Cryptococcal meningitis tmt (primary induction therapy + amphotericin B) Monitor peak levels 2 hours after dose at steady state (therapeutic range 25 - 100 mcg/mL) *BBW:* Use with extreme caution in patients with impaired renal function. Close monitoring of hematologic, renal and hepatic status of all patients is essential.

What is Fluconazole?

MOA: inhibits fungal sterol synthesis OI clinical uses: Oropharyngeal, esophageal candidiasis or vulvo-vaginal (primary) Suppressive therapy for candida infections (if meet criteria) Cryptococcal meningitis (primary consolidation therapy and maintenance therapy) Adverse effects: Hepatotoxicity Rash Nausea, vomiting, diarrhea, abdominal discomfort *Reversible alopecia (with doses ≥400 mg/d for >2 months)* QTc prolongation

What is Dapsone?

MOA: interferes with folate synthesis OI clinical uses: PCP ppx (alternative) PCP treatment (alternative, mild to moderate, given with TMP/SMX) Toxo ppx (alternative, needs to be combined with pyrimethamine/leucovorin) Adverse effects: Hematologic: methemoglobinemia, hemolytic anemia (especially in patients with G6PD deficiency), neutropenia *Patients should be tested for G6PD deficiency before starting therapy* Dermatologic reactions (including rash), sulfone syndrome (fever, exfoliative dermatitis, lymphadenopathy hepatic necrosis, hemolysis) Peripheral neuropathy Hepatotoxicity Drug-induced lupus erythmatosus Nephrotic syndrome Phototoxicity

What is Sulfadiazine?

MOA: interferes with folate synthesis OI clinical uses: Toxo tmt (primary, combined with pyrimethamine) Toxo secondary ppx/chronic maintenance (primary, combined with pyrimethamine) Toxo tmt and secondary ppx (alternative, combined with atovaquone) Adverse effects: *Rash (including SJS,TEN)* *Anemia, neutropenia, thrombocytopenia* Crystalluria, renal insufficiency Nausea, vomiting Drug fever Hepatotoxicity Headache, peripheral neuritis, tinnitus, vertigo, insomnia

48 hours later, he is improving clinically and will be extubated later this morning. A sputum culture obtained 2 days ago is growing the following: Light Growth: Staphylococcus aureus Recommend appropriate definitive therapy for this patient. Oxacillin resistant

MRSA, DC gram - coverage Continue Vanco

Which antibiotics are bacteriostatic- inhibit protein synthesis? (6)

Macrolides Tetracyclines Tigecycline TMP/SMX Clindamycin Linezolid

What are some key points about culture collection?

Make sure to get a good specimen Community acquired - Low utility of cultures in general Healthcare associated infection - Gram stain might help determine presence of yeast Further work-up required for moderate to heavy growth of specific organisms

What are the Risk Factors for IE?

Male (2:1) Prosthetic valves Intracardiac devices Unrepaired cyanotic congenital heart disease History of endocarditis Chronic rheumatic heart disease Age related degenerative valvular lesions Hemodialysis Diabetes HIV IV drug use

What is the duration of therapy based on the organism? Do not need to memorize

May need to be individualized based on pt response 1. Streptococcus pneumoniae: 10-14 days 2. Neisseria meningitidis: 7 days 3. Listeria monocytogenes: >21 days 4. Haemophilus influenzae: 7 days 5. Streptococcus agalactiae: 14-21 days 6. Aerobic gram - bacilli: 21 days - In neonates, >3 weeks or 2 weeks beyond first sterile CSF culture whichever is longer

What is meningitis?

Meninges made up of 3 layers - Dura, arachnoid and pia mater Meningitis - Inflammation of the meninges - Results in morbidity (seizures, etc.) and mortality

What is Cellulitis?

Microbes breach the cutaneous surface Predisposing factors - Fragile skin, Diminished local host defenses - Obesity - Previous cutaneous trauma - Prior episodes of cellulitis - Edema from venous insufficiency - Lymphedema - Most common in the lower legs Cultures of blood, cutaneous aspirates, biopsies or swabs are NOT usually recommended Duration of antimicrobial therapy should be 5 days May be extended if not improved in this time 1. Purulent S. aureus usually Purulent drainage or exudate in absence of a simple, drainable abscess 2. Non-Purulent Usually caused by Streptococci Group A most common, but also B, C, G , F No purulent drainage, exudate or associated abscess

What are some Antimicrobial Restrictions?

Minimize frequency, duration, and number of antimicrobial agents Implement a stewardship program Adherence to infection control policies Reduction of unnecessary antimicrobials Restriction of fluoroquinolone, clindamycin and cephalosporins should be considered

What are the gram negative coccobacilli?

Moraxella catarrhalis

What is an OI?

More frequent or more severe infection in patients with HIV due to HIV mediated immunosuppression May be a newly acquired infection (bacterial respiratory disease) OR reactivation of a latent infection (varicella zoster virus disease) Opportunistic infections are serious and dangerous complications of HIV infection They have decreased significantly, but still occur Patients get OIs in part, because It might be their sentinel event leading to diagnosis They have unsuccessful viral suppression

What is Human Papillomavirus (HPV)?

Most common sexually transmitted infection in the US 40 distinct HPV types Persistent infections with some types of HPV can cause cancer and genital warts HPV 16 and 18 - 66% of cervical cancer - 25% of low grade and 50% of high grade cervical dysplasia HPV 6 and 11 - 90% of genital warts

What is Candidiasis?

Most common species C. albicans - resistance uncommon C. glabrata - fluconazole SDD C. tropicalis C. parapsilosis - enchinocandin resistance C. krusei - fluconazole resistant "Newer"- Candida auris

What are the Bacteria by Infection Type?

Most of these infections are caused by Gram + organisms on the skin 1. Erysipelas= Group A Atreptococci 2. Impetigo= Staphylococcus aureus and Group A Streptococci 3. Cellulitis= Staphylococcus aureus and Group A Streptococci 4. Necrotizing fasciitis Anaerobes, streptococci, Enterobacterales, Group A Streptococci, Clostridium perfringens 5. Diabetic foot infections S. aureus, streptococci, Enterobacterales, Bacteroides spp, Peptpstreptococcus spp and Pseudomonas aeruginosa 6. Pressure sores S. aureus, streptococci, Enterobacterales, Bacteroides spp, Peptpstreptococcus spp and Pseudomonas aeruginosa 7. Animal bites Pasteurella spp, S. aureus, streptococci, Bacteroides spp 8. Human bites Eikenella corrodens, S. aureus, strepococci, Bacteroides spp, Corynebacterium spp, Peptostreptococcus spp

What are the risk factors for HAP and VAP?

Multidrug resistant pathogens: IV antibiotic use in the past 90 days Septic shock at the time of VAP ARDS preceding VAP 5+ hospitalizations before VAP Acute renal replacement therapy prior to VAP

What are the therapeutic uses of rifampin?

Mycobacterial infections - TB and MAC (mycobacteria avium complex) Combination with other agents in infections associated with biofilms (prosthetic materials) - Resistance develops quickly when used as monotherapy

What is MAC?

Mycobacterium avium Complex (MAC) Caused mostly by M. avium (95% of cases) Ubiquitous in the environment Inhalation or ingestion from environment AIDS defining illness Highest incidence in CD4 count < 50 Clinical presentation: Looks like TB: fever, night sweats, wt loss, fatigue etc Diagnosis: Clinical presentation, AFB smear and culture (stool) and blood cultures

What is the Pathogenesis and Treatment Principles of brain/epidural Abscess?

NO GUIDELINES Pathogenesis: Contiguous, hematogenous or direct inoculation Treatment: Combination of antibiotics AND surgery because it can rupture into the ventricles which increases mortality

What are the Syphilis treatments?

NOTE: DESENSITIZE TO PCN WHEN POSSIBLE 1. Primary, secondary, or early latent < 1 year Benzathine PCN G 2.4 million units IM X 1 Alt: Doxycycline 100 mg PO BID OR tetracycline 500 mg PO QID for 14 days 2. Latent > 1 year, latent of unk duration Benzathine PCN G 2.4 million units IM q wk x 3 doses Alt: Doxycycline 100 mg PO BID OR tetracycline 500 mg PO QID for 28 days 3. Pregnancy Pregnant women should be treated with the PCN regimen appropriate for their stage of infection No alternative, need PCN 4. Neurosyphilis Aqueous crystalline PCN G 18 - 24 million units/day (divded every 4 hours or as continuous infeusion for 10 - 14 days Alt: Procaine PCN G 2.4 million units IM daily PLUS probenecid 500 mg QID for 10 - 14 days

What is the treatment for Gonorrhea?

NOTE: Should include treatment for C. trachomatis due to high co-infection rate 1. Adults, adolescents: uncomplicated infection of the cervix, urethra and rectum and pharyngeal Ceftriaxone 250 mg IM once PLUS azithromycin 1 gm ONCE Alt: Cefixime 400 mg PO once PLUS azithromycin 1 gm ONCE 2. If conjunctivitis, Change ceftriaxone to 1 g IM PLUS azithromycin 1 g ONCE Alt: If ceph allergy: Gemifloxacin 320 mg PO once PLUS azithromycin 2 g ONCE OR Gentamicin 240 mg IM once PLUS azithromycin 2 g ONCE

What covers MSSA AND Streptococcus spp?

Nafcillin/oxacillin (6) Dicloxacillin (6) Dori, erta, mero +/- vab Cephalosporins (1) Clindamycin (2) Quino/dalfo 1. Ceftazidime and ceftaz/avi are NOT reliable against MSSA or Viridans group strep (VGS), cefprozil is NOT reliable against VGS, cefixime is NOT reliable against MSSA, ceftolo/tazo has insufficient data to recommend for MSSA, cefiderocol is GRAM NEGATIVE only 2. Clindamycin is NOT reliable against VGS 6. Not reliable against VGS

What is the pathogenesis of meningitis?

Nasopharynx Spread from local infection or bacteremia Penetrating head trauma that introduces bacteria Foreign body

What are the Nuances of Treatment of IE?

Native vs prosthetic Organisms: Inoculum effect Duration Treatment: Drug penetration, Static vs cidal drugs (cidal may be more beneficial to sterilize vegetations with higher densities)

What are the TDM Reminders?

Need to interpret levels with caution What are some potential reasons for unreliable results? Think about and we'll discuss in class

What is the Empiric Therapy for a brain/epidural Abscess?

Needs to have aerobic and anaerobic activity Examples: Penicillin, ampicillin +/- sulbactam, cefuroxime, ceftriaxone, ceftazidime, cefepime, vancomycin, meropenem and metronidazole

What are the gram negative cocci?

Neisseria gonorrhoeae Neisseria meningitidis

What are the ADEs for Polymixins?

Nephrotoxicity- monitor with other renally impairing drugs Neurotoxicity

How does healthcare associated ventriculitis and meningitis present?

New headache, nausea, lethargy, and/or change in mental status Erythema and tenderness over the subcutaneous shunt tubing Fever, peritonitis, pleuritis, bacteremia, in absence of another, clear source

What ONLY covers Enterococcus faecalis?

Nitrofuratonin

What is the Duration of Therapy for CABP?

No less than a total of 5 days Guided by validated measure of clinical stability Resolution of vital signs, ability to eat and normal mentation

What are PPIs and CDI?

No recommendation for PPIs Although there is an epidemiological association between proton pump inhibitors use and CDI, and unnecessary PPIs should always be discontinued, there is insufficient evidence for discontinuation of PPIs as a measure for preventing CDI

What is The NOTA Study?

Non - Operative Treatment for Acute Appendicitis (NOTA) Prospective, observational study Observation instead of surgery Included 159 patients and were followed for 2 years Amoxicillin/clavulante 1 gm PO TID for 5 -7 days was effective in preventing surgery in 88% of patients

70 yo woman presents to the clinic with lower urinary tract complaints (dysuria, increased frequency and superpubic heaviness). She is afraid that she has another UTI, this would make it her 3rd in the last 6 months. She wants to know what she can do to prevent getting more UTIs in the future that does not require her taking an antibiotic. What information would you provide her?

Non-antimicrobial Cranberry? Potentially effective in ASB during pregnancy Topical estrogen? Post menopausal women Probiotics? Lactobacillus spp in post menopausal women

What are the Candidiasis Recommendations?

Non-neutropenic and neutropenic patient DOC: echinocandin Alt: fluconazole (if no azole exposure) or AmB Candidemia recommendations: 14 days after first NEGATIVE blood culture Dilated fundoscopic exam CVC removal on individual basis if source

TF is a 37 yo male (90 kg, 74 in, NKA) who presents to the ED with a 2 day history of redness and swelling of his left lower leg PMH is negative Currently takes no medication. PE: his leg is red, warm to the touch, without any purulence noted. Labs: WBC 16, scr 1, Vitals: temp 100.4, BP 130/75, RR 17 He is admitted for cellulitis What type of infection dose this patient have? (Objective 2) What are the most like organisms causing this patient's infection? (Objective 1) Recommend an appropriate empiric treatment regimen (Objective 3) Two days later, he is afebrile, his WBC have normalized, the redness has much improved What is an appropriate length of therapy for him?

Non-purulent Moderate cellulitis with signs of infection IV with Penicillin and Ceftriaxone GAS 5 days

What is the Empiric Treatment of endocarditis?

Not recommended per current guidelines unless patient condition warrants If warranted, then target most likely organism Per Sanford guide *Native valve: vancomycin plus either ceftriaxone or gentamicin* *Prosthetic valve: vancomycin plus gentamicin plus rifampin*

What are the Recommendations for the ARV Resistance Assays?

Not recommended upon entry into care for HIV If greater than 4 weeks has lapsed since the ARVs were discontinued, resistance testing may still provide useful information to guide therapy, recognizing that previously selected resistance mutations can be missed

Is imaging used for diagnosis for meningitis?

Not routinely recommended - Some patients at increased risk of adverse events from lumbar puncture (LP) therefore should undergo CT prior to LP - CT recommended in: immunocompromised, history of CNS disease, papilledema or selected focal neurological deficit SHOULD NOT delay initiation of antibiotic therapy

What is the ADE/monitoring for Quinupristin/Dalfopristin?

Not used often because of all this stuff: Can cause phlebitis - central line administration increased cost Myalgias and arthralgias DDI with CYP 3A4 Needs to mixed with D5W otherwise it'll crystallize in the IV

What is a "superbug"?

Old bacteria that have mutated and become resistant to some antibiotics

What is the Clinical Trials: Dolutegravir + 2 NRTIs vs. Darunavir/ritonavir + 2 NRTIs?

Once-daily dolutegravir was superior to once-daily darunavir plus ritonavir at 96 wks

What do you notice about the ART regimens?

One INSTI plus 2 NRTIs Biktarvy®: BIC/TAF/FTC Triumeq®: DTG/ABC/3TC if HLA-B 5701 negative Dovato®: STG/3TC INSTI plus one NRTI except when HIV RNA >50,000 copies/mL They are INSTI-based

What is the Anti-MRSA treatment?

Only indicated in patients with healthcare associated infection in specific patients Colonized with MRSA Previously failed treatment Significant abx exposure Vancomycin is the recommended agent

PR is a 78 yo male presents to the ED with fever and chills and a non-healing ulcer on his right foot PMH includes diabetes, COPD, HTN and asthma. 90 kg, NKA ROS: malaise, aches, high-grade fever and generalized weakness. Temp 101. 5, BP 94/69, HR 105, RR 22 Labs: WBC 14, CRP 12.6, Scr 6.6 What additional labs/information would you like? What type of infection dose this patient have? (Objective 2) What are the most like organisms causing this patient's infection? (Objective 1) Recommend an appropriate empiric treatment regimen (Objective 3) Resistant to Clindamycin and Erythromycin Based on the culture results, what modifications, if any would you make to this patient's regimen? (Objective 4) What is the total duration of therapy?

Osteomyelitis Staph Vanco pulse dosing based on renal function

What is osteomyelitis?

Osteomyelitis represents an inflammation of the bone marrow and surrounding bone Hematogenous vs contiguous vs direct inoculation Acute vs chronic Oldest evidence found in a Dimetrodon fossil 250 million years old First description of hematogenous spread 1773 by William Bromfield

What characteristics do gram negative bacteria have?

Outer membrane makes abx penetration difficult Stains pink/red LPS and peptidoglycan

What is Altered PBP?

PBP is important for the production of peptidoglycan Normally B-lactam antibiotics bind to the PBPs disabling their ability to form a functional cell wall Modification prevent this from occurring

What are some of the OIs?

PCP Toxoplasmosis MAC Cryptococcus CMV Candida

RC is a 80 yo male who presents to the ED with right hip redness that has progressed since this morning according to his wife. 63 kg, NKA. PMH: DM, HTN, sacral ulcer, CABG, bilateral shoulder and bilateral hip replacements "many years ago" Vitals: temp 102. 7 F, HR 78, RR 24, BP 123/71 PE: Right hip is red and edematous. Patient is lethargic What type of infection dose this patient have? (Objective 2) What are the most like organisms causing this patient's infection? (Objective 1) Recommend an appropriate empiric treatment regimen (Objective 3) Penicillin R Gentamicin S Levofloxacin R Clindamycin R Tetracycline S Oxacillin R Vancomycin S Tigecycline S Rifampin S Based on the culture results, what modifications, if any would you make to this patient's regimen? (Objective 4) What is the total duration of therapy?

PJI?- risk factors, ESR, CRP, synovial fluid analysis Staph *Need culture result before* we start ABX (definitive therapy only) Unless critically ill (septic shock, pressors)- this patient is not Culture back: Vanco + Rifampin (for biofilm penetration) Tigecycline not used because of BBW, getamicin is not monotherapy, rifampin is not monotherapy

What are the definitions of HAP vs CAP vs VAP?

PNA: Lung infiltrates PLUS clinical evidence of infectious origin 1. From community= CAP 2. Not present at time of admission AND occurs ≥48 hr after admission= HAP 3. Ventilated ≥48 hrs= VAP

A 65 yo male presents to his primary care physician in October for an annual physical evaluation. He has never received a pneumonia vaccination PMH: gout and hyperlipidemia What is your recommendation regarding immunizations for this patient?

PPSV23 today, make decision about PCV13 If they decide to do PCV13, get that one today then PPSV23 one year later

What is PSI?

PSI (Pneumonia Severity Index) Based on a history of diseases that increase risk of death Complicated to use Score >130, high risk inpatient admission

What is the Acute Bacterial Rhinosinusitis Management?

Patient diagnosed with uncomplicated acute bacterial sinusitis. Are severe symptoms present? Yes- urgent referral to treatment No- Can patient reliably return for follow-up in a week? If they can't follow-up- No, provide symptomatic care and initiate antibiotics If they can follow-up- Yes, provide symptomatic care and observe for 7 more days Did patient improve after 7 days? No, start ABX Severe symptoms: high persistent fever >102 F periorbital edema, inflammation, or erythema abnormal extraocular movements vision changes altered mental status

What is Risk of PCV serotypes is dependent on?

Patient underlying medical conditions Persons in nursing homes/LTC facilities Low pediatric PCV13 vaccinations Risk increases with age and persons with one or more of the following Chronic heart, lung, or liver disease, diabetes, or alcoholism, and those who smoke cigarettes or who have more than one chronic medical condition If you are caring for patients with any of the above, consider offering PCV13 if they have not previously received it

Her urine cultures come back growing > 100, 000 CFU/mL Klebsiella pneumoniae Ampicillin Resistant Amp/sulb Susceptibile Cefazolin Susceptible Cefepime Susceptible Ceftazidime Susceptible Ciprofloxacin Resistant Ertapenem Susceptible Gentamicin Susceptible Imipenem Susceptible Levofloxacin Resistant Meropenem Susceptible Nitrofurantoin Susceptible Piperacillin/tazobactam Susceptible Sulfamethoxazole/Trimethoprim Susceptible How would you modify this patient's antibiotics now? (definitive therapy) The patient is feeling better. They are no longer febrile and are ready to be discharged home

Patient wants to go home and ceftriaxone IV... DC ceftriaxone start Sulfamethoxazole/Trimethoprim PO BID for 14 days

What is PCN Skin Testing?

Patients who report a history of penicillin allergy, 80 - 90% have a negative penicillin skin test (PST) PST provides the likelihood of an IgE mediated hypersensitivity (anaphylaxis) reaction to PCN Step 1: Skin prick test - PCN determinant, PCN G, histamine and saline Step 2: if step 1 negative, intradermal testing as above

In-class Case 3: You have a patient that the team wants to start plazomicin for. You are unsure of the PK/PD parameters for this medication. What is the peak concentration and the AUC (0-∞) for a single dose of plazomicin 15 mg/kg? Were you able to find the answer? If so, where, specifically in the Sanford Guide? What is the answer?

Peak plasma concentration: 51-74 mcg/mL AUC: 226-257 mcg·hr/mL pg 98

What covers Streptococcus spp AND Enterococcus faecalis?

Penicillin G (6) Amp (6) Amox (6) 6. Not reliable against VGS

What are the bacteria friends in the colon?

Peptostreptococci Lactobacillus Bacteroides Candida Clostridia Fusobacteria

How is meningitis diagnosed with physical exams?

Physical exam findings: 1. Classic triad - fever, nuchal rigidity, and altered mental status 2. Kernig and Brudzinski signs- poorly sensed and often absent in children 3. Meningococcal specific signs - purpuric and petechial skin lesions (60% of adults and 90% of children have one or both). - Waterhouse-Friderichsen syndrome, the eruption of multiple hemorrhagic lesions associated with shock 4. Pneumococcal findings - Head trauma with or without skull fracture or presence of a chronically draining ear may be associated with pneumococcal infection.

How can PNA be prevented?

Pneumococcal vaccinations against Streptococcus pneumoniae Pneumococcal conjugate vaccine PCV13 or Prevnar13® Pneumococcal polysaccharide vaccine PPSV23 or Pneumovax23®

What is PCP?

Pneumocystis jirovecii pneumonia Previous name: Pneumocystis carinii pneumonia Atypical fungus Most antifungals are not effective because it lacks ergosterol Ubiquitous in environment Infection often occurs in early childhood Most common, life threatening OI Highest incidence when CD4 count < 200 AIDS defining illness Many are not diagnosed with HIV until they present with PCP

What is Bacterial Vaginosis?

Polymicrobial clinical syndrome caused by various anaerobes Presents with malodorous discharge Not sexually transmitted per se Increased risk with multiple sex partners, new sex partner, douching, lack of condom use and lack of vaginal lactobacilli

How can we use PRECISION MEDICINE to Guide ATAZANAVIR Therapy?

Potential UGT1A1 effects on RAL and DTG as alternative choices to ATV UGT1A1 PM= bilirubin-related discontinuation advised

What is the Diagnostic Testing in PJI?

Pre-operative blood tests - ESR, CRP, IL-6 Synovial fluid analysis Histopathological tests

What are the MAC Treatment Options?

Preferred: Need at least 2 anti-mycobacterial antibiotics for at least 1 year Clarithromycin (or azithromycin) + ethambutol Can add rifabutin IF any of the following: CD4 count < 50 High mycobacterial load (>2 log CFU/mL) Not on effective ART Alternatives to rifabutin: Levofloxacin, moxifloxacin, amikacin or streptomycin

What are the Toxo Treatment Options?

Preferred: Sulfadiazine + pyrimethamine + leucovorin for at least 6 weeks Alternatives: clindamycin + pyrimethamine + leucovorin, TMP/SMX, atovaquone + sulfadiazine OR pyrimethamine + leucovorin, or atovaquone monotherapy

What are Prosthetic joint infections?

Prosthetic joints improve quality of life PJI is a serious complication 1-2% risk over life of joint Most common types of PJI Total hip arthroplasties (THA) Total knee arthroplasties (TKA) Carry high economic burden

What are the breakpoints?

Quantitative values (MIC cutoffs) that separate categories of classification Numbers change based on the bug 1. Susceptible <2 mcg/mL 2. Intermediate - low level of resistance 4-8 mcg/mL 3. Resistant - high level of resistance >16 mcg/mL Varies based on organism-drug combination Example vancomycin and Staphylococcus aureus

What are the Characteristics of HIV Virion?

RNA Reverse Transcriptase Protease Integrase Capsid Matrix Lipid membrane gp 120 gp 41

CC: trembling, shakes and fever PHI: 72 yo male, has had a foley placed for 2 years, was doing well, presented today with fever and chills PMH: DM, HTN, hx of pyelo and UTIs, prostatic enlargement causing renal failure, ESBL + E. coli in urine from Nov 2014 ROS: feverish, chills and feeling cold PE: unremarkable WBC 9.6, BUN 44, scr 3.5, PCT 20.86 all others WNL UA: 4+ bacteria, 3471 WBC, neg nitrites Urine and blood cultures done Started on ceftriaxone Preliminary result: blood culture gram - rod and presumptive in all 4 bottles of 2 sets Strep agalactiae (Group B Strep) in all 4 bottles of 2 sets

ROS- fever, chills, bacteria in the urine True infection Probable bacteremia Ceftriaxone good for gram - coverage ESBL though so ceftriaxone might not be enough Could do carbapenem without ceftriaxone could do meropenem

What are the largest gaps in the HIV care continuum?

RSVP= retention in care leads to suppression of viral load and prevention of transmission Potential upcoming gap within the next year= prescribed ART to achieved viral suppression due to COVID and recession Largest Gap: Linkage= Engagement/retention in care • Racial/ethnic minorities • Passive referral to care • Lack of insurance • Stigma, discrimination • Poor access to services • Poverty, homelessness • Mental illness, substance abuse • Poor transitions from correctional facilities to community *Biggest problem is people linked in care to people retained in care*

What is the CCR5 Tropism Test?

Recommended before initiating maraviroc therapy Four different phenotypic recombinant virus assays (RVA) predict co-receptor usage Trofile® (Monogram Biosciences; San Francisco, CA) Results reported as R5+, X4+ or Dual-Mixed (R5+/X4+) Genotypic methods show high specificity (~90%), but modest sensitivity (~50%-70%) for a CXCR4-utilizing virus

Patient is discharged home on treatment for CDI She returns 3 weeks later with fever and diarrhea Classify her infection now and recommend appropriate treatment for her What else would you like to do for this patient?

Recurrent CDI switch van or fdx, depends on what you chose for initial or tapered

What is Genital Herpes Simplex?

Recurrent, painful genital and or/anal lesions Most genital infections are caused by HSV-2 while HSV-1 are orolabial &acquired during childhood

Why is diabetes a risk factor in pre-menopausal women?

Reduced immune function, can't fight infection

What is the ADE/monitoring for nitrofuratonin?

Renal function - CrCl cutoff has changed to < 30 ml/min per Beers criteria but not reflected in package insert Avoid in glucose-6-phosphate dehydrogenase deficiency GI effects- anorexia, N/V Peripheral neuropathy Pulmonary toxicity

What are the ADEs/monitoring for glyco/lipo?

Renal function (all) Vancomycin - TDM, review Clinical PK notes from Spring Daptomycin - CPK levels, rhabdomyolysis, renally dose adjusted based on *IBW crcl* Telavancin - *BBW for nephrotoxicity and increased mortality for HAP and VAP pts and also intra-fetal toxicity* Oritavancin - interferes with anticoagulation specifically warfarin metabolism

*What is Prior Authorization?*

Requires providers to get approval for certain antibiotics before they are prescribed Pros: Reduces initiation of inappropriate antibiotics Optimizes empiric choices Prompts review of clinical data/ prior cultures at the time of initiation of therapy Decreases antibiotic costs Provides mechanism for rapid response to antibiotic shortages Direct control over antibiotic use Cons: Impacts use of restricted agents only Impacts empiric >> definitive tmt Loss of prescriber autonomy May delay therapy Effectiveness depends on skill of approver Real-time resource intensive Potential for manipulation of system May simply shift to other antibiotic agents and select for different antibiotic-resistance patterns

What are the ABX for CABP?

Respiratory FQs Beta-lactams Macrolides Tetracyclines Antipseudomonal beta-lactams AntiMRSA Others not included in the updated guideline

What are the FQs for CABP?

Respiratory fluoroquinolones Levofloxacin 750 mg daily Moxifloxacin 400 mg daily Gemifloxacin 320 mg daily (outpatient only) Why not ciprofloxacin? Hint: It doesn't have to do with lung penetration Ciprofloxacin cannot be considered as a single-fluoroquinolone formulary option because it lacks activity against S pneumoniae

What are the Contraindications with Elvitegravir(EVG)/cobicistat(c):Considerations for Stribild®/Genvoya?

Rifamycins (rifampin, rifabutin and rifapentine) Lovastatin/Simvastatin/Lomitapide St. John's Wort

What is Recurrence?

Risk factors Previous UTI within 6 months Genetic predisposition Antibiotic use for ASB

Case: 49 yo female with uncontrolled diabetes is admitted to the hospital with flank pain, chills and a temperature of 101.4 F. The local antibiogram has a local resistance rate to E. coli of 18% to ciprofloxacin. She has no known drug allergies. What is this patient's risk factors for a urinary tract infection? How would you classify this patient's infection? What is the BEST empiric treatment regimen for this patient? Include dose, route, frequency and duration

Risk factors: Uncontrolled diabetes S/Sx: flank pain, fever, chills Pyelonephritis Empiric: Ceftriaxone 1 gm IV q days OR Aminoglycoside Resistance for FQ is too high (>10%)

HK is a 19 month old female, 10 kg, NKA, who lives at home with her parents and brothers in Tuscumbia AL. Presents with a 2 day history of high fever, lethargy, irritability, poor appetite and vomiting. She was born at 38 weeks gestation PE reveals an ill appearing toddler, temp 102.5 F with a diffuse petechial rash She is sent for an LP and further work-up for meningitis LP is positive for bacteria and 4500 WBC What is/are this patient's risk factors for a CNS infection? Additional questions that you would like to ask? How would you classify this patient's infection? What is the BEST empiric treatment regimen for this patient? What organisms are you concerned for? Include dose, route, frequency and duration Monitoring? What is your recommendation for adjunctive steroids for this patient? The patient is diagnosed with N. meningiditis meningitis The family wants to know if they are at risk for getting this too. What is your recommendation for prophylaxis? Any additional questions?

Risk factors: Young, big family, no vaccines Community acquired Bacterial Vanco+3rd generation cephalosporin like ceftriaxone Prophylaxis: Haemophilus influenzae Rifampin 600 mg PO daily x 4 doses Neisseria meningiditis Ceftriaxone 250 mg IM x 1 Rifampin 600 mg PO BID x 4 doses Cipro - if no resistance, 500 mg PO x 1

52 year old male with relapsed, acute myeloid leukemia (AML) presents with cough and fever 2 months after starting salvage chemotherapy He is not currently taking antibacterial or antifungal prophylaxis Labs: ANC 200 cells/mm3 Scr 0.6, wt 65 kg, ht 70 in, NKA Imaging: small lobe infiltrate on chest X-ray Patient is initiated on broad spectrum antibiotics appropriate for febrile neutropenia. On day 3 of treatment, the patient has persistent fever and rapidly decompensated. The patient had a seizure and was treated with lorazepam and phenytoin. The patient was transferred to the ICU. High resolution CT revealed multiple hypodense lesions in the brain and lung What are this patient's risk factors for invasive fungal infection? What are the most likely organisms? What additional diagnostic labs would you like to get?

Risk factors: immunocompromised due to chemo Organisms: aspergillus or cryptococcosis Diagnostic labs: 1-3 beta-D-glucan tests or galactomann

34 yo pregnant female presents at her OB office for her second trimester OB visit (24 weeks gestation). She is asked to provide a urine sample. A urine dipstick reveals leukocytes and nitrates. Upon further questioning and examination, she reports no systemic signs of infection or urinary symptoms. What is this patient's risk factors for a urinary tract infection? How would you classify this patient's infection?

Risk factors: pregnancy Complicated cystitis

What are the Protease Inhibitors (PIs) CYPs?

Ritonavir Substrate: CYP3A4, CYP2D6 Inhibitor: CYP3A4, CYP2D6 (less) Inducer: CYP1A2, 2B6, 2C8, 2C9, 2C19 and UGT1A1

What is the Flucytosine TDM?

Routine during first week, draw peak at 3 - 5 days Indicated in patients with renal insufficiency and/or poor response Goal: peak 20 - 50 mg/L Efficacy: Peak > 20 mg/L Safety: Peak < 50 mg/L

What is the Itraconazole TDM?

Routine during first week, draw trough at approx 7 days Indicated in patients with GI dysfunction and DDI Prophylaxis > 0.5 mg/L (trough) Treatment > 1-2 mg/L (trough)

39 yo male with a history of congenital urethral stricture presents to the ED with urinary complaints of chills, dysuria, increased urinary frequency and pelvic pain for 2 days. He also notes pain upon defecation. He has an elevated temperature of 102.3 F and WBC of 14. A urine culture is collected and sent for susceptibility testing. On physical exam his prostate is enlarged and tender What is this patient's risk factors for a urinary tract infection? How would you classify this patient's infection? What is the BEST empiric treatment regimen for this patient? Include dose, route, frequency and duration

S/Sx: Chills, dysuria, increased urinary frequency, pelvic pain, fever, elevated WBC, congenital urethral structure Acute prostatitis Empiric: Cefriaxone 1-2 gm IV q 24 hours, follow with PO FQ for 2-4 weeks

CC: "I have to urinate a lot and it hurts when I do" HPI: a 19 year old female presents to the urgent care walk-in clinic with dysuria and polyuria for the last 3 days PMH: seasonal allergies Surgical Hx: none FH: non-contributory SH: Attends college, currently a junior. Smokes tobacco and marijuana on the weekend x 2 years, drinks alcohol socially on the weekends x 1 year, sexually active with boyfriend of 8 months, uses condoms Allergies: sulfa = rash and blisters Home medications: Ethinyl estradiol/etonogestrel vaginal ring - remove every 21 days then repeat 7 days later Cetirizine 10 mg PO daily Phenazopyridine hydrochloride 200 mg PO TID Vitals: Temp 98.4 deg F, HR 62, RR 15 BPM, BP 112/82, 66 in, 52.3kg General: thin, well nourished, NAD, AAO x 3 HEENT: WNL Pulm: WNL CV: WNL Abdominal: WNL GU: normal female genitalia, complaints of dysuria, denies hematuria. No malodorous discharge noted from vagina Neuro: WNL Extremities: Edema in bilateral lower extremities Back: no tenderness to palpation on lower lumbar region Urinalysis, dipstick Macroscopic: yellow, cloudy, large leukocytes, positive nitrites, pH 8 Microscopic: WBC > 100, RBC 0, squamous epithelial cells 0 Cultures: Urine Gram stain: Gram negative rods, identification and susceptibilities pending Assessment: What is a likely sign or symptom of a urinary tract infection for this patient? How would you classify this patient's infection What is (are) the most likely bacteria responsible for this patient's infection? Plan: Select an appropriate empiric regimen for this patient Make sure to include appropriate monitoring parameters

S/Sx: Urinary frequency Uncomplicated cystitis Nitrofurantoin or sulfamethoxazole/trimethoprim

*Why do you think that patients with HIV have higher rates of adverse effects than patients without HIV?*

SMX/TMP causes increased skin sensitivity and patients who are immunocompromised will be at higher risk for skin irritation since their skin wont heal as well T lymphocyte sensitivity with HIV, specifically to trimethoprim. As CD4 counts get lower, they dont have as much hypersensitivity

What treatments are available for necrotizing fasciitis?

SURGICAL EMERGENCY Broad spectrum abx Narrow once susceptibilities known 1. Monomicrobial streptococcal pyogenes Penicillin plus clindamycin 2. Clostridial spp Penicillin plus clindamycin 3. Vibrio vulnificus Doxycycline plus ceftazidime 4. Aeromonas hydrophilis Doxycycline plus ciprofloxacin 5. Polymicrobial Vanco plus piperacillin/tazo

What are the Antipseudomonal Beta-Lactams for CABP?

Same as per HAP/VAP guidelines Piperacillin/tazo 4.5 gm IV q 6 hrs Cefepime 2 gm IV q 8 hrs Ceftazidime 2 gm IV q 8 hrs Imipenem/cilastatin 500 mg IV q 6 hrs Meropenem 1 gm IV q 8 hrs Aztreonam 2 gm IV q 8 hrs

What is ASB?

Screening and antibiotics indicated in: Pregnant women Urological intervention TURP Renal stone intervention Who should NOT be screened or treated for ASB: Older persons in LTCF Functionally or cognitively impaired (delirium) Diabetic Transplant patients Neutropenic patients Spinal cord injuries Urethral catheters or urological devices

See Venn Diagrams

See Venn Diagrams

What is the The Multi-state Fungal Meningitis Outbreak?

Sept 2012, Tennessee Department of Health New England Compounding Center (NECC) in Framingham, MA Preservative free methylpredisolone acetate Initial infections: Aspergillus fumigatus Subsequent infections: Exserohilumrostratum

What additional testing should be done with CABP?

Severe CABP Blood cultures Sputum culture Urinary antigen for Legionella and Streptococcus pneumoniae

What is a Healthcare Associated Intra-abdominal infection?

Should be driven by local susceptibilities Will probably need more broad antibiotics 1. Community onset - Presence of invasive device - Hx of MRSA infection or colonization - Hx of surgery, hospitalization, dialysis or long term care facility (12 mo) 2. Hospital onset - 48 hr after admission

What are the Fluoroquinolones for UTIs?

Should be reserved for pyelonephritis and complicated UTIs FDA BBW High probability for collateral damage Only can use empirically where resistance rates are < 10% CANNOT use moxifloxacin Common side effects: nausea/vomiting, diarrhea, headache, drowsiness, insomnia

What are the therapeutic uses of FQs?

Should not be used in certain conditions (acute sinusitis, acute bronchitis, and uncomplicated urinary tract infection) unless there are no alternatives Common disease states: CAP, UTI - All have activity for Enterobacterales - Ciprofloxacin, levofloxacin, delafloxacin all have activity against Pseudomonas aeruginosa - Ciprofloxacin lacks S. pneumoniae activity (no CAP) *NOT A RESPIRATORY FQ DUE TO THIS*

What are Recurrent Abscesses?

Should prompt search for local causes - Pilonidal cyst - Hidradenitis suppurativa - Foreign material Drained and cultured early 5 - 10 day course of targeted antibiotics 5 day decolonized regimen twice daily intra-nasal mupirocin, daily chlorhexidine washes, daily decontamination of personal items

What are the Consequences of Antibiotic Use?

Side effects from antibiotics Allergic reactions Heart rhythm disturbances (FQ) Bone marrow suppression (SMX/TMP) Peripheral neuropathy (nitrofurantoin) Antibiotic associated diarrhea Clostridioides difficile infection (CDI)

What is the ADE/monitoring for Monobactams?

Similar to other beta-lactams Low incidence of hypersensitivity

What is the Pathophysiology of ABSSSIs?

Skin/subcutaneous tissues are usually resistant to infection A healthy skin microbiome protects itself by not allowing the colonization of more pathogenic strains Certain conditions can predispose to ABSSSIs High bacterial concentrations Excessive moisture Inadequate blood supply Availability of bacterial nutrients Corneal layer skin damage

What is Pelvic Inflammatory Disease (PID)?

Spectrum of inflammatory disorders of the upper female genital tract Endometritis, salpingitis, tub-ovarian abscess and pelvic peritonitis Organisms NG and CT Vaginal flora Others

What is the ADE/monitoring of rifampin?

Stains contacts and body fluids orange Major CYP inducer - Need to monitor for DDI (3A4, 2C19, 2D6) - Metabolizes some drugs to subtherapeutic levels like oral contraceptives, cyclosporine, warfarin, phenytoin, theophylline, digoxin, azole antifungals - Sometimes increasing dose isn't sufficient to overcome the CYP induction - Need to adjust doses back down when they go off rifampin

What are the Common Bacteria in PJIs?

Staph aureus and Coag-neg staph ~ 50 - 60% of all PJI 50/50 each Strep and enterococci ~10% of all PJI Aerobic Gram negative bacilli <10% of cases Culture negative ~15 % Polymicrobial ~15%

What bacteria are common in IE? (3)

Staphylococcus aureus (~26%) Streptococcus spp Enterococcus spp

What are the principals of C diff treatment?

Stop antimicrobials Start treatment for CDI Place patient on contact precautions Supportive care

In-class Case 4: A patient presents with acute mastoiditis, their first episode What are the most likely bacteria causing this infection? What is the recommended empiric treatment? Were you able to find the answer? If so, where, specifically in the Sanford Guide? What is the answer?

Streptococcus pneumoniae and non-typable Haemophilus influenzae, Moraxella catarrhalis Treatment: ceftriaxone or levo are recommended pg 13

How does the HIV testing care and continuum differ between the US and Africa?

Strikingly similarities between Africa and America given the bulk of global population living with HIV (2/3rds ) are in Africa

Why is dori-penem not commonly used?

Study vs Imipenem for VAP, increased risk of death with doripenem so study stopped Doripenem now has warning for VAP

What is Mucormycosis (zygomycosis)?

Subphylum Mucoromycotina Rhizopus spp (47%) Mucor spp (18%) Subcutaneous infections localized to sinuses, head, trunk or arms from minor trauma Risk factors Immunocompromised DM with high blood sugars Immunocompetent following trauma

What are the Two-Drug ART Strategies?

Successful regimens for persons with SUPPRESSED HIV switching from three-to-two drug regimens 1. DTG and RPV (reasonable when NRTIs are not desirable) 2. DTG and 3TC 3. PI/r and 3TC 4. Boosted DRV and DTG (only if there are no other treatment options)

What are the risk factors for Candidiasis?

Surgery TPN Fungal colonization Renal replacement therapy Infection Mechanical ventilation Diabetes APACHE II or III score

What should be considered with Hospitalization and IE?

Suspicion for IE requires hospitalization Consider IE in patients with unexplained fever and known risk factors Febrile IVDU should be evaluated for bacteremia and IE Patients with prosthetic valve and fever New murmur or change in murmur with evidence of vasculitis or embolization

What are the Clinical Manifestations of C diff?

Symptomless carriage Mild to moderate diarrhea Fulminant, sometimes fatal pseuomembranous colitis Extraintestinal-rare

*What are the Notable DDIs with NRTIs?*

Tenofovir Alafenamide (TAF) and CYP3A4/P-gp Inducers -AUC of TAF is DECREASED in the presence of the following CYP3A4/P-gp inducers: -Anticonvulsants (oxcarbazepine, carbamazepine, phenobarbital, phenytoin) -Rifamcyins (rifabutin, rifampin, rifapentine) -St John's Wort -Tipranavir/ritonavir -*Co-administration of these therapeutic agents with TAF is NOT recommended* -*However, TDF can be safely co-administered with these agents* *Rilpirivine and Doravirine have less side DDI compared to the rest of the NNRTIs à less adverse reactions expected*

What is Diverticulitis?

The presence of the infection and inflammation of a diverticulum - Develops in 10 - 25 % of people with diverticulosis Usually present with anorexia, left lower quadrant pain and fever Few data exist supporting antimicrobials in uncomplicated diverticulitis Complicated diverticulitis should be treated like secondary peritonitis

What is the bacterial meningitis Prophylaxis?

These are spread by respiratory droplets, not aerosol. Requires close contact to spread, often used as post-exposure prophylaxis for healthcare or roommates Can't give rifampin to pregnant women 1. Haemophilus influenzae Rifampin 600 mg PO daily x 4 doses 2. Neisseria meningitidis Ceftriaxone 250 mg IM x 1 Rifampin 600 mg PO BID x 4 doses Cipro - if no resistance, 500 mg PO x 1

What characteristics do gram positive bacteria have?

Thicker wall of peptidoglycan Stains blue/purple

What is the Time to Positivity (TTP)?

Time to positivity is the time it takes for the blood cultures to become positive Affected by amount of bacteria present in blood and type of bacteria (more bacteria= quicker time to positive) False positives are more likely if growth occurs after 72 hours - Few true blood stream infections are detected after 48 hours- takes about 24 hours max *Different bacteria take different amounts of time*

The patient's culture comes back with fluoroquinolone resistant N. gonorrhoeae. It was sensitive to ceftriaxone and cefixime What treatment do you recommend for this patient? (definitive therapy) What additional recommendations do you have for this patient?

Treat the partner AND the patient Ceftriaxone 250 mg IM once PLUS azithromycin 1 gm ONCE Or Cefixime 400 mg PO once PLUS azithromycin 1 gm ONCE The FQ not recommended- inappropriate ABX therapy Someone who is treated can still have a positive NAAT weeks later If someone received Ceftriaxone 1 gm IV, what would you say? It's fine, not recommended but they are done with treatment

What is a CA-UTI?

Treat with same antibiotics as complicated cystitis 7 days in patients with prompt resolution of symptoms 10 - 14 days in patient with delayed treatment response 5 days of levofloxacin in non-severely ill 3 days may be considered for patients ≤ 65 without upper tract symptoms after catheter has been removed

What is the Aspergillosis Treatment?

Treatment Preferred Voriconazole Alternative AmB (ok if voriconazole is unavailable) Isavuconazole Echinocandins (for salvage therapy, not as monotherapy for primary treatment) Duration 6 - 12 weeks

What is Antibiotic Therapy based off for osteomyelitis?

Treatment based on identification of pathogen from: Previous pathogen based on medical history Contiguous mechanism may be polymicrobial Gram-neg. & anaerobic bacteria common in diabetic foot infections Cultures/bone biopsy Empiric therapy - Can consider waiting if osteo is more chronic in nature - May not be able to isolate organisms from infection

What helps to Determine Appropriate Treatment Choices?

Treatment of HIV is INDIVIDUALIZED; Identification of Adherence Barriers helps to Determine Appropriate Treatment Choices

*What is the mechanism of TMP/SMX induced hyperkalemia?*

Trimethoprim decreases potassium excretion through competitive inhibition of epithelial sodium channels in the kidney (similar to the action of amiloride), and may cause hyperkalemia in certain susceptible patients

What is TMP/SMX?

Trimethoprim/Sulfamethoxazole OI clinical uses: PCP treatment (primary) PCP ppx (preferred) Toxo treatment (alternative) Toxo ppx (preferred)

What is the Voriconazole TDM?

Troughs only Correlate with efficacy and toxicity Trough range: 1 - 5.5 mg/L < 1 mg/L associated with clinical failure in Aspergillus infx > 4 mg/L associated with toxicity (hepatotoxicity and encephalopathy)

Cobicistat-boosted PIs are associated with fewer DDIs than ritonavir boosted PIs? T/F

True

Cross reactivity of penicillin to first generation cephalosporins is very low (~1%) and decreases as the generation increases. T/F

True

Lovastatin and simvastatin should not be used with all PIs and cobicistat-boosted INSTIs T/F

True

Raltegravir and dolutegravir are associated with less DDIs than cobicistat- boosted INSTI EVG T/F

True

Those who receive PrEP should have follow-up HIV testing q 3 months + Bacterial STI testing q 3-6 months T/F

True

True or false: Congenital syphilis has increased in the United States over the last few years.

True

True or False: Primary prophylaxis is defined as preventing infection by starting drug prophylaxis before the patient has the disease

True Secondary- has/had disease, prevent recurrence after patient has completed treatment for disease

True or False: It is important to add adjunctive corticosteroids within 72 hours of starting treatment for severe cases of PCP, since this has shown to improve survival and decrease the risk of respiratory failure.

True FIO2 cut off is 70 mmHg

What is the Pathophysiology of IE?

Turbulent flow states cause damage to vascular endothelium This causes formation of sterile vegetations Vegetations become infected due transient bacteremia Some organisms can directly invade endocardium causing formation of an infectious vegetation Especially with cocaine use

What are the therapeutic uses for TMP/SMX?

UTI (resistance rates at institution determine if this is first line or not) PCP (Pneumocystis pneumonia) ABSSSI- esp MRSA Listeria meningitis Toxoplasmosis

What is Aspergillosis?

Ubiquitous in the environment Common species: A. fumigatus, A. flavus, A. terreus and A. niger Risk factors Profound, prolonged neutropenia Transplant patients Advanced AIDS Other severely immunocompromised conditions

What is Cystitis or Pyelo?

Uncomplicated vs complicated Complicated increases infection severity and risk of failure Diabetes, pregnancy, late diagnosis, structural abnormality, renal obstructions and immunosuppression

What is the duration of therapy for osteomyelitis treatment?

Up to 6 weeks of antimicrobial therapy May switch from IV to PO with high bioavailability Chronic Osteo or no surgical intervention Consider additional 1-3 months of oral combination therapy Rifampin + susceptible oral antibiotic MRSA - Minimal duration of 8 weeks is recommended Amputation - 2-5 days antimicrobial therapy post-amputation

*What are the lines on the log concentration graph?* Assessment question

Up to down: 1. Control (golden line) 2. Bacteriostatic (blue dashed line) 3. Bacteriostatic (purple) 4. Bactericidal (green) >3 log reduction from the control

How is a UTI diagnosed?

Urinalysis Clean catch Pyuria is nonspecific and does not always include clinical UTI Bacteriuria ≠ infection Nitrates Certain spp reduce nitrate to nitrite in the urine

Is urine sterile?

Urine microbiome studies have proven that urine is not sterile Some data suggests bacteriuria is protective Host response to bacteria varies Culture only if there is high suspicion for UTI

What are the therapeutic uses of clindamycin?

Usually alternative in infections caused by Gram positive organisms - ABSSSI - Intra-abdominal infections (anaerobes) Oral infections Malaria (combination) Bacterial vaginosis

What is the PK/PD Data with HAP/VAP?

Usually higher doses than manufacturer Antibiotic blood concentrations Extended and continuous infusions Weight based dosing

What is Pancreatitis?

Usually not an infectious process and does not require antimicrobials Other causes of pancreatitis: alcohol, medication, hyperlipidemia, autoimmune, idiopathic Antimicrobials should be reserved for severe, secondary cases infections and peritonitis Non-necrotic and necrotic without infection do not need antibiotics Necrotic with infection - need 4 - 7 days of tmt

CC: Headache, fever and chills HPI: a 67 year old woman with pertinent PMH of RA on infliximab and prosthetic aortic valve who was brought to the ED with lethargy and confusion. She has been complaining of fever, chills and headaches for the past 2 days. PMH: CAD, depression, DM type 2, HTN, fibromyalgia, aortic stenosis with valve replacement Surgical Hx: bioprosthetic aortic valve replacement 10 months ago, tubal ligation and cholecystectomy (both > 15 years ago) FH: Father passed away from HF, mother has DM type 2, HTN and stroke, sister has DM type 2 SH: widowed, lives alone, never used alcohol former smoker (>15 years ago) Allergies: hydrocodone/APAP = n/v Home medications: Aspirin 81 mg PO daily Atorvastatin 20 mg PO daily Fluoxetine 40 mg PO daily Glimepiride 4 mg PO daily Infliximab 3 mg/kg IV every 2 months Lisinopril 10 mg PO daily Pregabalin 75 mg PO BID Vitals: temp 102.1 deg F, HR 112, RR 19, BP 91/52, ht 165 cm, wt 91 kg General: lethargic, acutely ill appearing, appears stated age HEENT: faint conjunctival hemorrhage, poor dentition Pulm: clear CV: RRR, faint systolic murmur over the right base Abdominal: tenderness in the epigastric region to palpation GU: deferred Neuro: AO x 1, no focal deficits, strength and sensation full and symmetric Extremities: intact distal pulses, no LE edema Labs: Na 124 mmol/L, K 3.4 mmol/L, BUN 28 mg/dL, Scr 1.4 mg/dL. Cl 88 mmol/L, CO2 19 mmol/L, Glucose 286 mg/dL WBC 21.3 K/microL, Segs 72%, bands 22% CT Head: unremarkable, no evidence of infarct or hemorrhagic stroke *Transthoracic echocardiogram (TTE):* LVEF 73%, normal RV systolic function, AV appears to be well seated with normal functioning and trace regurgitation, no pulmonary hypertension or pericardial effusion seen, Cultures: Blood, LP/CSF - pending ED course: has LP done that reveals meningitis is less likely. Blood cultures become positive with GPC in clusters - awaiting identification and susceptibility Assessment: What is a likely sign or symptom of IE for this patient? Is there another test/imaging modality that you would recommend to make the diagnosis clearer? What is (are) the most likely bacteria responsible for this patient's infection? Plan: Select an appropriate empiric regimen for this patient Make sure to include appropriate monitoring parameters

VALVE REPLACEMENT and Immunosuppression Do a TEE Gram positive Most likely organism: Staph aureus or epidermidis Treatment: vanco + rif+genta Green tube= no growth Red tube= growth *Need one bottle in each set to be positive to be a true infection* *Contamination= depends on organism, time to growth* Letter A: 1/4 bottles positive Letter B: 2/4 bottles positive/Both bottles of 1 set positive or 1 set positive (one aerobic+ anaerobic) Letter C: 2/4 bottles positive/one bottle in each set/aerobic bottle in each set is positive Letter D: 3/4 bottles positive (both anaerobic+one aerobic) Letter E: 4/4 bottles positive

What is Val/Ganciclovir?

Valganciclovir (PO) is the prodrug of ganciclovir (IV) MOA: inhibit DNA synthesis OI clinical uses: CMV retinitis tmt (primary) Intravitreal injection (w/PO) PO (+/- intravitreal injection) CMV retinitis chronic maintenance therapy (primary) *BBW* potential teratogen and carcinogen Adverse effects: *Neutropenia, thrombocytopenia, anemia* Injection-site-associated thrombophlebitis Increased serum creatinine *Carcinogenic and teratogenic potential, impaired fertility* Neuropathy

The following culture results come back: CSF Culture, Streptococcus pneumoniae Vancomycin 0.5 Sensitive Levofloxacin 4 Intermediate Penicillin 2 Resistant Ceftriaxone 1 Intermediate Clindamycin 0.5 Intermediate

Vanco is good for strep Resistant to ampicillin Keep Ceftriaxone because vanco not supposed to be monotherapy

Why is vancomycin combined with a 3rd generation cephalosporin for empiric treatment for most age groups? Hint: Staph aureus is NOT the answer

Vanco: Strep pneumoniae, 3rd gen cephalosporin for gram - coverage Vancomycin doesn't cover N. meningitidis but a third gen cephalosporin would (because it is gram - and vanco doesn't have gram - activity)

What are the AntiMRSA ABX?

Vancomycin 15 mg/kg q 12 hrs - Adjust based on levels Linezolid 600 mg q 12 hrs

What is VISA?

Vancomycin-Intermediate Staph. aureus Extremely rare Occurs with selection pressure Cell wall changes cause trapping of vancomycin Susceptibility returns after medication is discontinued 90% of VISA are still susceptible to minocycline, tigecycline, telavancin and linezolid

What Monitoring/Safety needs to be considered?

Vancomycin: AUC (2015 IE guidelines rec troughs) Gentamicin: troughs Daptomycin: CPK B-lactams: delayed hypersenstivities, drug fever (usually 7 - 10 days), Cdiff Nafcillin/oxacillin: acute interstitial nephritis Linezolid: serotonin syndrome, myleosupression, thrombocytopenia especially after 2 weeks

What are the therapeutic uses of Cephalosporins?

Variable based on agent - Cefazolin/cephalexin have reliable activity against MSSA (alternatively anti-staph PCN is good) - Cefoxitin/cefotetan (the Cephamycins) have reliable activity against many anaerobes (like intra-abdominal inf. or dental) - Ceftazidime (+/- avibactam), cefepime, ceftolozane-tazo and cefiderocol have reliable activity against Pseudomonas aeruginosa - Ceftaroline has reliable activity against MRSA, use in *polymicrobial infections* with MRSA and Gram negatives

How common are UTIs?

Very common Especially in young, sexually active women Women > men

What is the recommendation of prophylaxis for IE?

Weak recommendation for dental procedures involving manipulation or perforation of oral mucosa Does not include: - Routine anesthetic injections through non-infected tissues - Dental radiographs - Placement or adjustment of orthodontic devices - Trauma to teeth or lips Most likely pathogens are VGS and ppx should be targeted towards this prior to procedure 1. Amoxicillin PO 2. IV/IM ampicillin, cefazolin, ceftriaxone

What is the RESISTANCE TO NNRTIS?

With K103N mutation, can still use active ARVs rilpivirine, etravirine or doravirine

What is the duration of therapy for intra-abdominal infections?

With adequate source control - 4-7 days of tmt - Longer durations have not been associated with improved outcomes Bowel injuries from penetrating, blunt or iatrogenic trauma, repaired within 12 hours - Should be treated for ≤ 24 hours Acute appendicitis without evidence of perforation, abscess or local peritonitis - Requires only ppx - All abx should be dc'd within 24 hours

What is the syphilis Jarisch - Herxheimer reaction?

Within 24 hours after antibiotic treatment of the spirochetal infections syphilis, Lyme disease, leptospirosis, and relapsing fever (RF), patients experience shaking chills, a rise in temperature, and intensification of skin rashes

How is Chlamydia diagnosed?

Women - First catch urine or endocervical or vaginal swabs Men - first catch urine or urethral swab Anatomical site exposure testing

Why does urinary incontinence or functional/mental impairment increase risk for UTI in post menopausal women?

Worse hygiene, diapers, lack of tone in urinary incontinence so bacteria can easily enter

What are the DFI Bacteria?

Wounds tend to be colonized 1. Mild cases Monomicrobial with Staph spp and Strept 2. Severe cases Polymicrobial with anaerobes, Pseudomonas aeruginosa and MRSA

Prior Respiratory Isolation of MRSA or Pseudomonas (PsA)?

Yes Non-severe/Severe MRSA: add MRSA antibiotic PsA: add antipseudomonal beta-lactam No- No, No additional abx needed Recent Hospitalization AND IV antibiotics AND Locally Validated Risk Factors for MRSA and/or PsA Yes- Non-severe Only start abx if cultures + for MRSA and/or PsA Severe MRSA: +MRSA antibiotic PsA: + antipseudomonal beta-lactam

Which of the following require treatment for asymptomatic bacteriuria? Select all. a. 67 yo male undergoing a TURP procedure b. 24 yo female sexually active female c. 36 yo pregnant woman d. 65 yo post-menopausal woman

a. 67 yo male undergoing a TURP procedure c. 36 yo pregnant woman

Which of the following pairs represent a drug interaction that requires a dose adjustment of RIFABUTIN to 150 mg daily or 300 mg TIW? a. ATV (atazanavir):Rifabutin b. ETR (etravirine):Rifabutin c. DOR (doravirine):Rifabutin d. EVG (elvitegravir):Rifabutin

a. ATV (atazanavir):Rifabutin

This measures the integrated concentration over time of total drug exposure. a. AUC/MIC b. T>MIC c. Cmax/MIC

a. AUC/MIC

Mary is a 35 years old female who is currently being treated for encephalitis. She is 60 in and weighs 43 kg. Her doctor is figuring out the dose of acyclovir to give her. He should use her: a. Actual Body Weight b. Body Surface Area c. Ideal Body Weight d. Adjusted Body Weight

a. Actual Body Weight

a. Ibalizumab-uiyk (Trogarzo®, IBA) ________ b. Fostemsavir (Rokubia®, FTR) ________ c. Tenofovir disoproxil fumarate (Viread®, TDF) ________ d. Abacavir (Ziagen®, ABC) ________ e. Darunavir (Prezista®, DRV) ________ f. Doravirine (Pifeltro®, DOR) ________ g. Rilpivirine (Edurant®, RPV) ________ h. Raltegravir (Isentress®, RAL) ________ i. Dolutegravir (Tivicay®, DTG) ________ Bictegravir (BIC, Co-formulated in Biktarvy®) ________

a. CD4-directed post-attachment inhibitor b. GP120-directed attachment inhibitor c. NRTI d. NRTI e. PI f. NNRTI g. NNRTI h. INSTI i. INSTI j. INSTI

Which of the following are the stages of treatment for cryptococcal meningitis? a. Induction, consolidation and maintenance b. Induction, treatment and prophylaxis c. Treatment, prevention and avoidance d. Consolidation, maintenance and prophylaxis

a. Induction, consolidation and maintenance

Which of the following micro-organisms are commonly implicated in community acquired bacterial pneumonia? Select ALL that apply. a. Influenza b. Streptococcus pneumoniae c. Staphylococcus aureus d. Acinetobacter baumannii

a. Influenza b. Streptococcus pneumoniae

Which of the following laboratory parameters should be monitored for a patient receiving amphotericin B to assess for amphotericin B related side effects? a. Magnesium b. Potassium c. Serum creatinine d. LFTs (liver function tests)

a. Magnesium b. Potassium c. Serum creatinine

Which species of bacteria has the highest number of isolates reported in the antibiogram? a. Staphylococcus aureus b. Pseudomonas aeruginosa c. Escherichia coli d. Enterococcus faecium

a. Staphylococcus aureus

Which of the following prophylaxis regimens have activity against BOTH toxoplasmosis and PCP? a. TMP/SMX b. Atovaquone c. Dapsone d. Aerosolized pentamidine

a. TMP/SMX b. Atovaquone

Patient follow up. The physician wants to start therapy for TR. He is located in an unit of the hospital where the MRSA rate is 30% among all Staph aureus isolates. Which of the following is the MOST appropriate recommendation? a. Vancomycin + piperacillin/tazobactam b. Linezolid + amikacin c. Piperacillin/tazobactam d. Cefepime + tobramycin

a. Vancomycin + piperacillin/tazobactam

MF has an infection caused by MSSA (methicillin susceptible Staph aureus). Which of the following would be the most appropriate choice? a. dicloxacillin b. moxifloxacin c. ampicillin d. methicillin

a. dicloxacillin

This drug has a warning associated with an increased risk of death in ventilator associated pneumonia and low clinical cure rates vs comparator. a. doripenem b. Ertapenem c. imipenem d. relebactam

a. doripenem

Which of the following is the more common type of vancomycin intermediate Staphylococcus aureus seen clinically? a. hVISA (heterogeneous vancomycin intermediate Staph aureus) b. VISA (vancomycin intermediate Staph aureus)

a. hVISA (heterogeneous vancomycin intermediate Staph aureus)

TB was recently diagnosed with a urinary tract infection. He is in the emergency room and doesn't feel right. His doctor noticed he has prolonged QT intervals. The medication most likely to cause this is: a. levofloxacin b. nitrofurantoin c. clindamycin d. meropenem

a. levofloxacin

Which of the following agents has activity against many Gram negative anaerobes such as Bacteroides fragilis? a. metronidazole b. clindamycin c. nitrofurantoin d. quinupristin/dalfopristin

a. metronidazole

This CDC Core Element involves overseeing the influence of interventions, antibiotic prescribing and outcomes like C. difficile infections. a. tracking b. accountability c. education d. action

a. tracking

Which of the following is the preferred treatment for pyelonephritis? a. SMX/TMP b. Ciprofloxacin c. Moxifloxacin

b. Ciprofloxacin Moxifloxacin is not excreted into the urine, no urinary penetration. Not a good FQ for UTI

Which of the following is a risk factor for primary toxoplasmosis infection? a. Unprotected sexual intercourse b. Eating undercooked meat c. Exposure to an indoor cat d. Gardening

b. Eating undercooked meat

TR is a 65 year old male admitted to the hospital 3 days ago for a femur fracture following a motor vehicle accident. Today he is noted to have a fever (101.5 F), cough, and infiltrate on chest x-ray. He is diagnosed with PNA Which of the following is the MOST appropriate classification for his PNA? a. Community acquired bacterial pneumonia b. Hospital acquired pneumonia c. Ventilator associated pneumonia

b. Hospital acquired pneumonia

Which of the following may be adequately treated with I&D (incision and drainage) alone? a. Impetigo b. Mild, purulent cellulitis c. Erysipelas d. Moderate, non-purulent cellulitis

b. Mild, purulent cellulitis

Which of the following is a common bacteria in complicated UTIs? a. Bacillus cereus b. Pseudomonas aeruginosa c. Providencia stuartii d. Candida albicans

b. Pseudomonas aeruginosa

Which of the following antibiotic classes used in CABP has activity against atypical pathogens? Select all that apply. a. Beta-lactams b. Respiratory fluoroquinolones c. Tetracyclines d. Macrolides

b. Respiratory fluoroquinolones c. Tetracyclines d. Macrolides

Which of the following is a pre-disposing risk factor for UTIs in pre-menopausal women? a. Urinary catheterization b. Sexual intercourse c. Estrogen deficiency d. History of UTI

b. Sexual intercourse a. Urinary catheterization - post menopausal c. Estrogen deficiency - post menopausal

Which of the following have been shown to prevent recurrent UTIs in post-menopausal women? Select all. a. Cranberry b. Topical estrogen c. Lactobacillus

b. Topical estrogen c. Lactobacillus Cranberry is for pregnancy

A common resistance mechanism for Gram positive bacteria like Streptococcus pneumoniae is: a. mutations in lipopeptide structure b. altered PBPs c. aminoglycoside modifying enzymes (AME) d. loss of porins

b. altered PBPs

JM is an 18 day old child who is suspected to have bacterial meningitis. What empiric antimicrobial therapy would be most appropriate? a. vancomycin, ampicillin and ceftriaxone b. ampicillin, tobramycin and cefotaxime c. vancomycin and ceftriaxone d. vancomycin and cefazolin

b. ampicillin, tobramycin and cefotaxime

Which antibiotic would be a good option to treat a skin and soft tissue infection caused by MRSA and VRE? a. delafloxacin b. oritavancin c. ceftaroline d. nitrofurantoin

b. oritavancin

The bacterial species Mycoplasma will stain _________ using a Gram stain: a. purple b. translucent c. pink

b. translucent

A 20 yo female has a positive urine culture with E. coli. How would you classify her infection? a. Uncomplicated cystitis b. Complicated cystitis c. Asymptomatic bacteriuria d. CA-UTI

c. Asymptomatic bacteriuria Need s/s for UTI

The above Gram negative coffee bean shaped diplococci are: a. Listeria monocytogenes b. Streptococcus pneumoniae c. Neisseria meningitidis d. Haemophilus influenzae

c. Neisseria meningitidis

Increasing clarity of Antibacterial stewardship programs and developing relationships with colleagues is a positive effect of which ASP intervention: a. Prior Authorization b. Pharmacy Accountability Plan c. Prospective Audit and Feedback d. Facility Specific Treatment Recommendations

c. Prospective Audit and Feedback

Which of the following is the MOST frequently described adverse effect to TMP/SMX in patients with HIV? a. Thrombocytopenia b. Hyperkalemia c. Rash d. Hepatitis

c. Rash

In patients with HIV, PCP usually presents in this organ system: a. CNS b. GI/GU c. Respiratory d. Cardiac

c. Respiratory

If you decided, Dr. P, MD and Dr. M, R.Ph were going to be the leader and co-leader of an Antibiotic Stewardship Program. Which CORE Element would you be representing? a. tracking b. action c. accountability d. reporting

c. accountability

LC has a Streptococcus pneumoniae ear infection. Which of the following would be the most appropriate antibiotic to treat his infection? a. nitrofurantoin b. metronidazole c. amoxicillin d. doxycycline

c. amoxicillin

This member of the ASP is responsible for identifying the multi-drug resistant organisms (MDROs) within the population, conducting surveillance and monitoring/report MDRO trends over time a. Infectious disease physician b. IT specialist c. hospital epidemiologist d. microbiologist

c. hospital epidemiologist

Which of the following terms is used as a category when reporting susceptibility breakpoints? a. minimum b. symptomatic c. intermediate d. inhibited

c. intermediate

Which of the following antibiotics has activity against Pseudomonas aeruginosa? a. penicillin b. linezolid c. levofloxacin d. metronidazole

c. levofloxacin

This antibiotic inhibits folate synthesis which inhibits DNA synthesis. a. ceftriaxone b. imipenem/cilastatin c. trimethoprim/sulfamethoxazole d. ampicillin/sulbactam

c. trimethoprim/sulfamethoxazole

Which of the above shows the best activity against this organism? Kirby Bauer zones of inhibition a. No zone b. Little zone c. Medium zone d. Big zone

d. Big zone Biggest zone= most activity

Nitrofurantoin would most likely be used to treat an infection caused by: a. Acinetobacter baumannii b. Streptococcus spp c. MSSA (methicillin susceptible Staph aureus) d. Escherichia coli

d. Escherichia coli

Prescribers may feel a loss of independence under this Antibacterial stewardship program intervention. a. Facility Specific Treatment Recommendations b. Prospective Audit and Feedback c. Pharmacy Accountability Plan d. Prior Authorization

d. Prior Authorization

A broth dilution is defined as: a. a qualitative susceptibility test that gives a MIC b. a qualitative susceptibility test that gives a MBC c. a quantitative susceptibility test that gives a MBC d. a quantitative susceptibility test that gives a MIC

d. a quantitative susceptibility test that gives a MIC Kirby Bauer does not give MIC

If you interviewing a patient who reports that they were hospitalized and intubated due to a penicillin allergy, which strategy for allergy delabeling would you be using? a. graded challenges b. penicillin skin testing c. education d. allergy reconciliation

d. allergy reconciliation

The microbiologist as a member of the ASP is responsible for: a. co-leader assisting with day to day activities and reporting outcomes b. compliance with hand hygiene c. integrating interventions into the EMR d. developing antibiograms and diagnostic stewardship

d. developing antibiograms and diagnostic stewardship

Disadvantages of being labeled with a penicillin allergy include: a. decreased use of vancomycin, FQ and clindamycin b. shorter length of stay c. increased incidence of intubation d. increased number of VRE colonization and infections

d. increased number of VRE colonization and infections

If a patient had community acquired pneumonia (CAP), which of the following would be a good empiric agent for inpatient, non-severe CAP: a. cephalexin b. cefazolin c. cilastatin d. levofloxacin

d. levofloxacin

TS is a 68 year old female who presents to the pharmacy to get a "pneumonia shot". She thinks that she may have gotten it before but her PCP told her she needs another one. You look in your pharmacy record and see that she received PPSV23 6 years ago only. PMH: diabetes Which of the following is the MOST appropriate recommendation regarding pneumonia vaccination for this patient? a. Give PPSV23 today and PCV13 in 1 year b. Give PCV13 today and PPSV23 in 1 year c. Only PPSV23 is indicated d. Only PCV13 is indicated e. Engage the patient in shared decision making for PCV13 f. Neither PCV13 or PPSV23 are indicated

e. Engage the patient in shared decision making for PCV13

65 yo male, NKA, wt 80 kg presents to the ED with a 3 day history of headache, malaise, nausea and subjective fevers. He reports a 1 week history of nasal congestion and rhinorrhea. PE reveals some confusion, temp 102.1 F, HR 100, BP 90/65 and RR 20. CNS fluid from LP has opening pressure of 470 mmHg, 3300 WBC (75% PNMs), protein 160 mg/dL, glucose 40 mg/dL (serum glucose 160) What is/are this patient's risk factors for a CNS infection? How would you classify this patient's infection? (community, healthcare AND bacterial vs viral) What is the BEST empiric treatment regimen for this patient? What organisms are you concerned for? Include dose, route, frequency and duration Monitoring?

headache, malaise, nausea and subjective fevers, confusion Infection is bacterial due to high WBC Polymorphonuclear leukocytes, or PMNs, are a special family of white blood cells. Low glucose= bacteria food Community- Bacterial Empiric: Vanco, Amp, Ceftriaxone Organisms: 50

19 yo male, 70 kg, NKA, was admitted to the neurosurgery ICU 12 days after after a MVA. He sustained multiple injuries including an epidural hematoma. A craniotomy was performed with an external ventricular drain placed to remove excess CSF. After some initial improvement, his mental status declined and he is febrile (tmax 101.9 F). He is cultured: blood, urine, sputum and CSF What is/are this patient's risk factors for a CNS infection? How would you classify this patient's infection? What is the BEST empiric treatment regimen for this patient? What organisms are you concerned for? Include dose, route, frequency and duration Monitoring?

healthcare associated ventriculitis and meningitis Staph aureus, gram neg bacilli vanco + cefepime

What is hVISA?

heterogeneous Vancomycin-Intermediate Staph. aureus Resistant subpopulation of S. aureus that exists in a population of fully susceptible isolates Frequently MIC dependent Implications - Therapeutic failure - High inoculum infections MIC: 1 hVISA: 0% MIC: 1.5 hVISA: 14% MIC: 2 hVISA: 30% MIC: 3 hVISA: 80%

How common are Acute bacterial skin and skin-structure infections (ABSSSIs)?

one of the most common infections In 2009, 600,000 hospitalizations Emergency Room visits have increased Increased incidence of Community Acquired Methicillin Staphylococcus aureus (CA-MRSA) infections

What is a situation in which a DRV-based regimen may still be preferred?

when a high genetic barrier to resistance is particularly important, such as when there is substantial concern regarding a person's adherence or when antiretroviral therapy (ART) should be initiated before resistance test results are available.

Which antibiotics are bactericidal- cell wall active agents?

β-lactams (Penicillins, Cephalosporins, Carbapenems) Aminoglycosides Fluoroquinolones Metronidazole Daptomycin Vancomycin

What are the FDA Approved NRTIs?

•*Abacavir (ABC) - Ziagen®* •*Emtricitabine (FTC) - Emtriva®* •*Lamivudine (3TC) - Epivir®* •*Tenofovir disoproxil fumarate (TDF)- Viread®* •*Tenofovir alafenamide (TAF)- Vemlidy®* •Didanosine (ddI) - Videx® •Stavudine (d4T) - Zerit® •Zidovudine (AZT) - Retrovir®

What are the Factors to Consider for First Antiretroviral Regimen Selection?

•*Co-morbidities* •*Coinfections (HBV, HCV and TB)* •Pregnancy potential •*Adherence potential* •*Regimen's genetic barrier to resistance* •Convenience (pill burden, dosing frequency, availability of FDC formulations, food requirements) •Potential adverse effects •Cost and access •*Potential drug-drug interactions* •*Results of genotypic drug resistance testing* •Co-receptor tropism assay if considering maraviroc •HLA-B*5701 testing if considering abacavir •Psychosocial factors •Timing of initiation of ARV treatment

What are the Potential Adherence Barriers?

•*Depression* •Stigma •Substance abuse •Disclosure of HIV status •Transportation •Financial resources •Palatability of liquid formulations •*Pill burden* •*Dosing frequency* •Food requirement •Treatment fatigue •*Pill characteristics* •*Side effects* •Different languages

What is the Entry/CCR5 Inhibitor: Maraviroc (Selzentry®, MVC)?

•*Indicated for BOTH Tx-naïve and Tx-experienced HIV patients* •150, 300mg tablets •Dose: 300 mg PO BID (no food restriction) *if given with CYP3A4 inhibitors: 150mg PO BID* *If given with CYP3A4 inducers: 600mg PO BID* •t1/2 ~ 14-18 hrs •Metabolized by CYP3A4, P-gp substrate •Side effects: *hepatotoxicity (black box)*; orthostatic hypotension; cough; pyrexia; rash; small risk of infections (URI and HSV) •Drug Interactions: With EFV, rifampin double maraviroc dose With RTV, ATV, SQV, ketoconazole ↓ maraviroc dose by 50% No change with TPV/RTV, NVP, OCPs

What are the Integrase Strand Transfer Inhibitors (INSTIs)?

•*Raltegravir (RAL)- Isentress®* •*Dolutegravir (DTG)- Tivicay®* •*Elvitegravir (EVG)- Co-formulated in Stribild® and Genvoya®* •*Bictegravir (BIC)- Co-formulated in Biktarvy®*

What are the Protease Inhibitors (PIs)?

•*Ritonavir (RTV)- Norvir®* •Lopinavir + Ritonavir (LPV/r)- Kaletra® •*Atazanavir (ATV)- Reyataz®* •*Atazanavir/cobicistat (ATV/c)- Evotaz®* •Fosamprenavir (FPV, F-APV)- Lexiva® •Saquinavir (SQV)- Invirase® •Nelfinavir (NFV)- Viracept ® •Indinavir (IDV)- Crixivan® •Tipranavir (TPV)- Aptivus® •*Darunavir (DRV)- Prezista®* •*Darunavir/cobicistat (DRV/c)- Prezcobix®*

When to Change ARV Therapy?

•*Virologic Failure:* The inability to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL. •Incomplete virologic response defined as two consecutive plasma HIV RNA levels >200 copies/mL after 24 weeks on ART •*Sustained viral* rebound in a patient previously undetectable *Critical Next Steps to Consider:* •Rule out non-adherence to ARVs •Antiretroviral Resistance

What is the Acute Bronchitis Summary?

•Acute Bronchitis is usually caused by a viral pathogen and only symptomatic treatment should be recommended •The exception is in patients with confirmed or suspected pertussis infections, they should be provided a macrolide antibiotic.

What is Acute Retroviral Syndrome and Primary Infection?

•Acute HIV infection -Usually within 4-6 weeks after HIV exposure •Primary Infection Asymptomatic Fever (80-90%) Fatigue (70-90%) Rash (40-80%) Face and trunk Headache (32-70%) Lymphadenopathy (40-70%) Pharyngitis (50-70%) Myalgia or arthralgia (50-70%) GI symptoms (N/V) (30-60%) -Night Sweats (50%) -Hepatosplenomegaly (14%) -Neurological symptoms (12%) •encephalitis, ataxia -Oral ulcers or thrush (10-20%) -Genital ulcers (5-15%)

What are some Antimicrobial Stewardship Tips?

•Address patient concerns in a compassionate manner •Discuss the expected course of illness •Explain that antibiotics do not significantly shorten illness duration and are associated with ADEs and antibiotic resistance •Discuss treatment plan, including the use of nonantibiotic medications to control symptoms •Delayed Prescribing

How can you differentiate Differentiate Bacterial from Viral rhinosinusitis?

•Bacterial •Persistent (not improving for > 10 days) •Severe symptoms Worsening or 'double sickening'

What are the Long-Acting Cabotegravir and RiLpivirine After Oral Induction for HIV-1 Infection?

•CAB + RPV •Requires FDA approval for the investigational, monthly, injectable, two-drug regimen of cabotegravir and rilpivirine to treat HIV-1 •**FDA APPROVAL expected end of 2020**

How can AOM be prevented?

•Check for undiagnosed allergies and eliminate exposure to allergies and respiratory irritants •Vaccinate •haemophilus influnzae type B •pneumococcal conjugate •influenza •Placement of tympanostomy tubes

Should you use ABX in acute bronchitis?

•Cochrane Review: No net benefit to using antibiotics to treat acute bronchitis in healthy people •Study findings... •Antibiotics decreased - Cough duration by 0.46 days - Ill days by 0.64 days - Limited activity by 0.49 days •Antibiotics increased - Nausea, diarrhea, headache, skin rash, and vaginitis - Number needed to harm of 5

What are the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

•Delavirdine (DLV)- Rescriptor® •Nevirapine (NVP)- Viramune® •*Doravirine (DOR)- Pifeltro®* •*Efavirenz (EFV)- Sustiva®* •Etravirine (ETV)- Intelence® •*Rilpivirine (RPV)- Edurant®*

What are the Entry Inhibitors: Fostemsavir?

•GP-120 directed attachment inhibitor •New ARV class •Fostemsavir tromethamine is a prodrug that is hydrolyzed to active moiety temsavir •*Temsavir binds directly to gp120 subunit within HIV-1 envelope glycoprotein gp160 inhibiting the interaction between virus and CD4 cell receptors, thereby preventing attachment* •Temsavir also inhibits gp120-dependent post-attachment steps required for viral entry into host cells •Indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety consideration •Resistance considerations- both ibalizumab and fostemsavir develop resistance in gp120 •Administered as a single tablet of 600 mg *twice daily* •Most common adverse effect (≥ 5%) includes *nausea*

What is the Pharyngitis Summary?

•Group A Streptococcus is the only type of pharyngitis that needs antibiotic treatment •Patients should only receive antibiotics if they have a positive RADT or throat culture. •Penicillin or amoxicillin are first line treatments for patients without allergies

What are the Entry inhibitors: Ibalizumab-uiyk?

•Humanized IgG4 anti-CD4 monoclonal antibody (MAb) •Also known as TNX-355 and hu5A8 •Binds to domain 2 of CD4 T cell receptors, leading to conformational changes of CD4 T cell receptor-gp120 complex, thus, preventing HIV fusion and entry •Does *NOT* interfere with CD4-mediated immune functions (i.e. no immunosuppression) •Indicated for the treatment of HIV-1 infection in *heavily treatment-experienced adults with multidrug resistant HIV-1 infection* failing their current antiretroviral regimen •*Active against BOTH CCR5 and CXCR4 isolates* •NO cross-resistance with other entry inhibitors •Administered intravenously as a single loading dose of 2,000 mg followed by a *maintenance dose of 800 mg every 2 weeks* •Most common adverse effects (≥ 5%) include *diarrhea, dizziness, nausea, and rash*

What is the Symptom Management of acute bronchitis?

•Ibuprofen •Acetaminophen •Dextromethorphan •Guaifenesin •Honey •Recommended to avoid: •Codeine •Beta2 agonists (unless other lung condition present)

What are the Notable arv resistance Mutations?

•K65R=> tenofovir resistance •*K103N=> NNRTI resistance (efavirenz/nevirapine) EXCEPT etravirine, rilpivirine and doravirine* (*NEED TO KNOW*) •M184V=> lamivudine/emtricitabine resistance •D30N=> nelfinavir resistance •I50L=> atazanavir resistance •I84V=> extensive PI resistance •N155H=> raltegravir/elvitegravir resistance

What is the exception to not using ABX for acute bronchitis?

•Only time antibiotics should be considered for treatment of acute bronchitis is for pertussis infection. •If *pertussis* is confirmed or suspected because of a persistent cough accompanied by symptoms of paroxysmal cough, whooping cough, and post-tussive emesis, or recent pertussis exposure, *treatment with a macrolide is recommended*

How Did HIV Come to Infect Humans?

•Retroviral infection of humans -*Zoonoses*, primate-to-human species jumping -HIV-1, HIV-2: occurred in Central & West Africa -Simian immunodeficiency virus (SIV) •HIV-1: chimpanzee (SIVcpz) •HIV-2: sooty mangabey (SIVsm) First appeared in US in 1980s

What is the monitoring for AOM?

•Safety •Adverse effects- diarrhea •Allergic reaction •Efficacy •Resolution of fever and otalgia •Should improve by 48-72 hours

How is HIV transmitted?

•Sexual contact with an infected person without using a condom (male or female) -HIV can enter through the lining of the vagina, vulva, penis, rectum, mouth •Sexual contact with someone with unknown HIV status -Including assault (rape) •Drug needle or syringe sharing •Contaminated fluid exposure -Accidental sticks or contaminated body fluid -Exposure through non-intact skin •Vertical Transmission -Mother to child •*Breastfeeding (very high risk)*

What is the presentation of acute bronchitis?

•Symptoms •**Cough** •Sputum production •Dyspnea •Headache •Fever •Symptoms are usually present for 2-3 weeks Rule out Asthma exacerbation COPD exacerbation Pneumonia

What is the Pharyngitis - Supportive Care?

•Systemic analgesics •Ibuprofen or acetaminophen •Throat lozenges •Topical anesthetic spray •Popsicles/ice cubes Warm beverages or soup

What is the AOM summary?

•The most common bacteria in AOM are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis •Many patients with AOM will get better without antibiotic therapy •First line treatment of AOM is high dose amoxicillin for patients without allergies or risk for resistance

What is the cause of acute bronchitis?

•Viral > 90% •Rhinovirus •Enterovirus •Influenza A and B •Parainfluenza •Coronavirus •Respiratory syncytial virus •Bacterial 1-10% •Of patients with a cough for > 2 weeks, 10% had evidence of Bordetella pertussis

What are the key points of upper respiratory tract infections?

•Virus are the most common cause of upper respiratory tract conditions •Antibiotics should only be prescribed when there is high suspicion of a bacterial cause or the patient is at high risk for complications

Who is PCV13 recommended for?

≥ 6 - 64 years CSF leak, cochlear implant, functional or anatomic asplenia, immunocompromised persons ≥ 65 years Immunocompromised persons, cochlear implant or CSF leak All others - based on shared clinical decision making

Who is PPSV23 recommended for?

≥ 6 - 64 years Chronic heart disease, chronic lung disease, DM, CSF, cochlear implant, alcoholism, chronic liver disease, cigarette smoking and immunocompromised persons ≥ 65 years All adults should receive