Infectious Diseases- NAPLEX

Daptomycin- Drug Dosing

- SSTI: 4 mg/kg daily - Bacteremia/Right-sided Endocarditis: 6 mg/kg daily - CrCl <30: Dose adjustment required

Heart/Endocarditis Common Bacterial Pathogens

- Staphylococcus aureus (including MRSA) - Staphylococcus epidermidis - Streptococci - Enterococci

CNS/Meningitis Common Bacterial Pathogens

- Streptococcus pneumoniae - Neisseria meningitidis - Haemophilus influenzae - Group B Streptococcus/E. Coli (young patients) - Listeria (young/old patients)

Upper Respiratory Common Bacterial Pathogens

- Streptococcus pyogenes - Streptococcus pneumoniae - Haemophilus influenzae - Moraxella catarrhalis

Folic Acid Synthesis Inhibitors

- Sulfonamides - Trimethoprim - Dapsone

Cephalosporins- Side Effects

- Seizures, with accumulation - GI upset, diarrhea - Rash, allergic reactions, anaphylaxis, serious skin reactions (SJS/TEN) - Acute interstitial nephritis - Myelosuppression with prolonged use - Increased LFTs - Drug fever

Travelers' Diarrhea- Treatment Overview

*Azithromycin* is preferred if dysentery is present. Quinolones (for 1 to 3 days), or Rifaximin (for 3 days) can be used if bloody diarrhea is not present. Adjunctive treatment, including antimotility agents (*Loperamide [Immodium]*), provide symptomatic relief but should NOT be used when bloody diarrhea is present. Traveler destination can impact the preferred treatment. In practice, always consult specific guidance.

Quinolones- Medications and Formulations

*Ciprofloxacin*- Tablet, Suspension, Injection, Ointment, Ophthalmic, Otic - *Cipro*, Cipro XR - Ciloxan Eye Drops - Cetraxal Ear Drops, Otipro Ear Drops - *Ciprodex Ear Drops*, Otovel Ear Drops - Cipro HC Ear Drops *Levofloxacin*- Tablet, Solution, Injection, Ophthalmic - *Levaquin* *Moxifloxacin*- Tablet, Injection, Ophthalmic - *Avelox*, Moxeza and Vigamax Eye Drops) Delafloxacin- Tablet, Injection - Baxdela Gatifloxacin- Ophthalmic - Zymaxid Eye Drops Gemifloxacin- Tablet *Ofloxacin*- Tablet, Ophthalmic, Otic - *Ocuflox* Eye Drops

Skin/Soft Tissue Common Bacterial Pathogens

- Staphylococcus aureus - Staphylococcus epidermidis - Streptococcus pyogenes - Pasteurella multocida - Aerobic/Anaerobic gram-negative rods (diabetics)

Bone and Joint Common Bacterial Pathogens

- Staphylococcus aureus - Staphylococcus epidermidis - Streptococci - Neisseria gonorrhoeae - Gram-negative rods (only in specific situations)

Cephalosporins Clinical Pearls

- *Ceftriaxone requires no renal adjustment* - Cefixime is available in a chewable tablet - *Ceftazidime/Avibactam* covers some carbapenem-resistant Enterobacteriaceae (CRE) - Cefiderocol should be increased to 2 grams q6hrs if CrCl is 120+ mL/min

Aminoglycosides- Monitoring

- *Drug levels, renal function, hearing tests* - Traditional dosing: Draw a trough levels right before (or 30 minutes before) the 4th dose. Draw a peak level 30 minutes after the end of the 30-minute drug infusion for the 4th dose. - Extended-Interval dosing: Draw a random level per the timing on the nomogram.

Metronidazoles- Side Effects, Clinical Considerations

- *Metallic taste* - Headache, nausea, dizziness - Furry tongue - Darkened urine - SJS/TEN Secnidazole-specific - *Vulvovaginal candidiasis* - Headache, nausea, diarrhea

Vancomycin- Side Effects

- Abdominal pain, nausea (oral route) - Phlebitis (irritation to vein) - Myelosuppression (neutropenia, thrombocytopenia) - Drug fever - Severe skin reactions (SJS/TEN)

Protein Synthesis Inhibitors

- Aminoglycosides - Macrolides - Tetracyclines - Clindamycin - Linezolid, Tedizolid - Quinupristin/Dalfopristin

Acute Otitis Media- Antibiotic First-Line Therapies and Dosing

- Amoxicillin 80-90 mg/kg/day in 2 divided doses - Amoxicillin/Clavulanate (may be considered in patients who have received Amoxicillin within the past 30 days): 90 mg/kg/day of Amoxicillin with 6.4 mg/kg/day of Clavulanate in 2 divided doses - Ceftriaxone 50 mg/kg IM or IV for 1 to 3 days (if vomiting or unable to tolerate oral medication)

Aminopenicillins- Clinical Pearls

- Ampicillin PO is rarely used due to poor bioavailability. Amoxicillin is preferred when switching from IV ampicillin to PO antibiotic. - Augmentin: Use a 14:1 ratio (amoxicillin to clavulanate) to decrease diarrhea caused by the clavulanate component. - IV ampicillin and Unasyn *must be diluted in NS only*

Cephalosporins- Warnings

- Anaphylaxis/hypersensitivity reactions - Some drugs can increase the INR in patients taking warfarin - *Cross sensitivity (<10%)* in patients with a penicillin allergy. Do not use cephalosporins in patients with a *Type 1 penicillin allergy* (swelling, angioedema, anaphylaxis). - Cefotetan contains a side chain called NMTT or 1-MTT (N-methylthiotetrazole) which can increase the risk of bleeding and cause a *disulfiram-like* reaction with alcohol ingestion.

Tetracycline Drug Interactions

- Antacids and other polyvalent cations (such as magnesium, aluminum, calcium, iron, and zinc), multivitamins, Sucralfate, Bismuth Subsalicylate, and Bile Acid Binding Resins can chelate and inhibit tetracycline absorption. Separate doses about either 1-2 hours before or 4 hours after taking one of these medications. - Dairy products contain calcium and can chelate as well. However, these products only need to be avoided 1 hour before or two hours after the tetracycline. - Lanthanum Carbonate (Fosrenol) can decrease the concentration of tetracycline derivatives. Take tetracyclines at least 2 hours before or after Lantanum. - Tetracycline is a major CYP2A4 substrate and a moderate inhibitor. Use caution with CYP3A4 inhibitors, which increase levels, and CYP3A4 inducers, which decrease levels. - Tetracyclines can enhance the effects of warfarin and neuromuscular blocking medications.

Quinupristin/Dalfopristin- Side Effects

- Arthralgias/Myalgias (up to 47% of patients) - Infusion reactions, including edema and pain at infusion site (up to 44% of patients) - Phlebitis (up to 40% of patients) - Hyperbilirubinemia (up to 35% of patients) - CPK elevations - GI upset - Increased LFTs

Tigecycline- Dosing, Administration

- IV: 100 mg for the first dose, then 50 mg every 12 hours - No adjustment needed for renal impairment BUT severe hepatic impairment requires an adjustment - The reconstituted solution should be a *yellow-orange color*. Discard if the solution is NOT this color. - Tigecycline should NOT be used in bloodstream infections, as it does not achieve adequate concentrations in the blood due to it being very lipophilic (drug distributes out of blood and into the tissues very quickly).

Polymyxin B Sulfate- Dosing and Administration

- IV: 15,000 to 25,000 units/kg/day divided every 12 hours, 1 mg is 10,000 units of Polymyxin B - CrCl <80: dose adjustment required

Macrolides- Clinical Pearls

- Azithromycin has better gram-negative coverage than Erythromycin - Clarithromycin has the best Gram-positive activity Common Uses: - All macrolides can be used for CAP, and as an alternative to a beta-lactam for strep throat - Azithromycin-specific: COPD exacerbations, combination therapy for gonorrhea, and prophylaxis for Mycobacterium Avium Complex. It is also drug of choice for severe travelers' diarrhea (including dysentery, diarrhea with bloody stools) - Clarithromycin-specific: used for treatment of H Pylori - Erythromycin-specific: Increases gastric motility and is used for gastroparesis QT Prolongation - Use Macrolides with caution in those with CVD, hypoK, hypoMg, and other QT prolonging medications (such as azole antifungals, antipsychotics, methadone, and quinolones). Drug Interactions - Clarithromycin and Erythromycin are strong CYP3A4 inhibitors, *lovastatin* and *simvastatin* are contraindicated (increased risk of muscle toxicity).

Cell Wall Inhibitors

- Beta-Lactams (Penicillins, Cephalosporins, Carbapenems) - Monobactams (Aztreonam) - Vancomycin, Dalbavancin, Telavancin, Oritavancin

Common Sites of Infection

- CNS/Meningitis - Upper Respiratory - Heart/Endocarditis - Skin/Soft Tissue (SSTI) - Mouth - Lower Respiratory (Community) - Lower Respiratory (Hospital) - Bone/Joint - Urinary Tract - Intra-Abdominal

Rifampin- Clinical Considerations

- Can cause orange/red discoloration of body secretions (sputum, urine, sweat, tears, teeth), which can stain contact lenses and clothing - Rifampin has MANY DDIs. Be aware of DDIs before starting - Rifabutin can replace Rifampin in some cases (e.g. HIV patients taking Protease Inhibitors)

Drugs of Choice- Acinetobacter Baumannii

- Carbapenems (except *Ertapenem*) - Ampicillin/Sulbactam - Minocycline, Tigecycline - Quinolones - SMX/TMP - Colistimethate, Polymyxin B

Other Antibiotics Requiring NO Renal Adjustment

- Chloramphenicol - Fidaxomicin - Eravacycline - Omacycline - Quinupristin/Dalfopristin - Rifaximin - Rifampin - Seracycline - Tedizolid - Tigecycline - Tinidazole - Vancomycin PO

Drugs of Choice- VRE Faecium

- Daptomycin - Linezolid - Quinupristin/Dalfopristin, Tigecycline CYSTITIS ONLY: Nitrofurantoin, Fosfomycin, Doxycycline

Daptomycin- Overview

- Daptomycin (Cubicin, Cubicin RF) is a cyclic lipopeptide. It binds to cell membrane components, causing rapid depolarization, which inhibits all intracellular replication processes (including protein synthesis), causing cell death. - Daptomycin has *concentration-dependent* antibacterial activity against most gram-positive bacteria, including MRSA, and Enterococci (including both species of VRE, E Faecium and E Faecalis). - Daptomycin is approved for complicated SSTIs, and MRSA bacteremia, including right-sided endocarditis. However, it should not be used to treat pneumonia, as the drug is inactivated in the lungs by the surfactant.

Carbapenems- Adverse Effects

- Diarrhea - Rash/severe skin reactions (DRESS) - Seizures with higher doses and in patients with impaired renal function (mainly Imipenem) - Bone marrow suppression with prolonged use - Increased LFTs

Drugs of Choice- MSSA

- Dicloxacillin, Nafcillin, Oxacillin - Cefazolin, Cephalexin (and other 1st or 2nd generation cephalosporins) - Amoxicillin/Clavulanate, Ampicillin/Sulbactam - Doxycycline, Minocycline - SMX/TMP

Urinary Tract Common Bacterial Pathogens

- E Coli, Proteus, Klebsiella - Staphylococcus saprophyticus - Streptococci - Enterococci

Acute Bacterial Meningitis (Community-Acquired) Treatment Overview

- Empiric antibiotic selection depends on the age and risk factors. Aggressive (high) doses are used to penetrate the CNS. - Antibiotic durations are pathogen-dependent: 7 days for N. Meningitidis and H. Influenzae, 10-14 days for S. Pneumoniae, and at least 21 days for Listeria monocytogenes. - Dexamethasone can be given 15-20 minutes *prior to or with the first antibiotic dose* to prevent neurological complications. The adult dose is 0.15 mg/kg (rounded to 10 mg) IV q6hrs. Steroid treatment should be continued for 4 days.

Intra-Abdominal Common Bacterial Pathogens

- Enteric Gram-negative Rods - Enterococci/Streptococci - Bacteroides species

Macrolides- Adverse Effects

- GI Distress (diarrhea, abdominal pain, cramping) - Taste perversion - Ototoxicity (RARE, but reversible) - Severe (but rare) skin reactions such as SJS, TEN, and DRESS

Quinolones- Coverage

- Gemifloxacin, Levofloxacin, and Moxifloxacin are referred to as the *respiratory quinolones* due to their enhanced coverage of S. pneumoniae and Atypical coverage. - Ciprofloxacin and Levofloxacin have enhanced Gram-negative coverage, including coverage of *Pseudomonas*. They are typically used in combination with another agent (e.g. a beta-lactam) when treating Pseudomonas empirically. - Moxifloxacin has enhanced gram-positive and anaerobic activity and can be used alone for mixed infections (e.g. intra-abdominal infections). However, Moxifloxacin is the only quinolone that CANNOT be used for UTIs. - Delafloxacin, a newer quinolone approved for skin infections, is active against MRSA. Other quinolones are notes to have activity against MRSA, but there is very high rates of resistance and generally should be avoided.

Macrolides- Contraindications

- History of cholestatic jaundice/hepatic dysfunction with prior use - Clarithromycin and Erythromycin: Do not use with LOVASTATIN or SIMVASTATIN, Pimozide, Ergotamine, or Dihydroergotamine - Clarithromycin: Concurrent use with Colchicine in patients with renal or hepatic impairment, history of QT Prolongation, or ventricular arrhythmia

Colistimethate Sodium- Dosing and Administration

- IM/IV: 2.5 to 5 mg/kg/day in 2 to 4 divided doses (dose is expressed in terms of Colistin base activity) - CrCl <80: Dose adjustment required - Colistin is an injection, BUT the injection solution can be used for Inhalation. If being used for inhalation, the solution must be mixed immediately prior to administration. - The dose of this medication can be expressed in THREE DIFFERENT WAYS: Units of Colstimethate, mg of Colstimethate, or mg of Colistin base activity. Assess the dose carefully before administration.

Cephalosporins- Monitoring

- Renal function - Signs of anaphylaxis with 1st dose - CBC, LFTs

Drugs of Choice- CA-MRSA SSTIs

- SMX/TMP - Doxycycline, Minocycline - Clindamycin (requires a D-test before use) - Linezolid

Quinupristin/Dalfopristin- Dosing, Administration, Drug Interactions

- IV: 7.5 mg/kg every 8 to 12 hours, infused over 60 minutes - There is no dose adjustment in renal impairment - Synercid should be diluted in D5W ONLY, and it should only be administered via a central line, such as a Peripherally Inserted Central Catheter (PICC) to avoid phlebitis. Drug Interactions - Quinuprisin/Dalfopristin is a weak CYP3A4 inhibitor, so it can increase the levels of CCBs, Cyclosporine, Dofetilide, and other medications metabolized by 3A4

Daptomycin- Side Effects, Drug Interactions

- Increased CPK - Abdominal pain - Pruritus - Chest pain - Edema - Hypertension - Acute Kidney Injury Drug Interactions - Additive risk of myopathy/rhabdomyolysis when used in conjunction with statins

Isoniazid- ADEs

- Increased LFTs (usually asymptomatic) - Drug-Induced Lupus Erythematosus (DILE) - Hemolytic anemia (detected with a positive Coombs test) - Agranulocytosis - Aplastic anemia - Hyperglycemia - Headache - GI upset - Pancreatitis - Severe skin reactions (SJS/TEN/DRESS) - Optic neuritis

Aminoglycosides- Boxed Warnings

- May cause nephrotoxicity and ototoxicity, causing hearing loss, vertigo, or ataxia. Avoid use of aminoglycosides in combination with other neurotoxic/nephrotoxic medications. - May cause neuromuscular blockade and respiratory paralysis. - May cause fetal harm if given in pregnancy

Drugs of Choice- Bacteroides Fragilis

- Metronidazole - Beta-lactam/Beta-lactamase Inhibitor - Cefotetan, Cefoxitin - Carbapenems - Tigecycline - Others (although reduced activity): Clindamycin, Moxifloxacin

Metronidazoles- Drug Interactions

- Metronidazole is a weak inhibitor of CYP3A4 and CYP2C9. Tinidazole is a minor substrate of CYP3A4. - Metronidazole and Tinidazole should not be used with alcohol during and for 3 days after discontinuation of treatment due to a potential disulfiram-like reaction - Metronidazole and potentially Tinidazole can increase INR in patients taking Warfarin

Mouth Common Bacterial Pathogens

- Mouth flora (Peptostreptococcus, Actinomyces) - Anerobic Gram-negative Rods (Prevotella, etc.) - Viridians group Streptococci

Quinolones- Adverse Effects

- Nausea, Diarrhea - Headache, Dizziness - Rash, Serious skin reactions (SJS/TEN) - Cardiac issues (aortic aneurysm/dissection, QT prolongation) - Endocrine issues (hypo/hyperglycemia) - Psychiatric disturbances (agitation, disorientation, lack of attention, nervousness, memory impairment, delirium) - Musculoskeletal weakness and toxicity - Hepatotoxicity (liver pain, jaundice, increased LFTs)

Aminoglycosides- Adverse Effects

- Nephrotoxicity (acute tubular necrosis) - Hearing loss (early toxicity associated with high-pitched sounds) - Vestibular toxicity (resulting in balance deficits)

Common Groups of Bacterial Organisms

- PEK - HNPEK - CAPES - Mouth Flora

Tedizolid- Dosing

- PO/IV: 200 mg QD for 6 days - NO DOSE ADJUSTMENT IN RENAL IMPAIRMENT - IV to PO ratio is 1 to 1 - Tedizolid is available as a tablet or an injection

Linezolid- Dosing

- PO/IV: 600 mg every 12 hours - NO DOSE ADJUSTMENT IN RENAL IMPAIRMENT - IV to PO ratio is 1 to 1 - Linezolid is available as a tablet, suspension, or an injection

Clindamycin- Dosing and Administration

- PO: 150 to 450 mg every 6 hours - IV: 600-900 mg every 8 hours - No dose adjustment needed in renal impairment - An induction test (termed D-test) should be performed on S aureus that is deemed "susceptible" to Clindamycin but is also resistant to Erythromycin. - A flattened zone between the disks (a positive D-test) indicates INDUCIBLE Clindamycin resistance and therefore should not be used.

Drugs of Choice- VRE Faecalis

- Penicillin G or Ampicillin - Linezolid - Daptomycin - Tigecycline - CYSTITIS ONLY: Nitrofurantoin, Fosfomycin, Doxycycline

Storage Requirements: Liquid Oral Antibiotics- Refrigeration Required After Reconstitution

- Penicillin VK - Ampicillin - Amoxicillin/Clavulanate - Cephalexin - Cefadroxil - Cefpodoxime - Cefprozil - Cefuroxime - Cefaclor - Ceftibuten - Vancomycin (Firvanq) - Valganciclovir (Valcyte)

Pharyngitis- Treatment

- Penicillin, Amoxicillin, or a 1st/2nd Generation Cephalosporin - If there's a beta-lactam allergy, use Clarithromycin, Azithromycin, or Clindamycin Treatment is for 10 days except if Azithromycin is used, then treatment is only 5 days.

Rifaximin- Side Effects

- Peripheral edema - Dizziness, headache, nausea - Flatulence, abdominal pain - Rash, pruritus

Sulfonamide Antibiotics- Side Effects

- Photosensitivity, skin rash - Hyperkalemia, false elevations in SCr (due to inhibition of tubular secretion of creatinine), renal failure - Hemolytic anemia (identified with a positive Coombs test) - Crystaluria (take with 8 oz of water) - N/V/D, anorexia - Decreased folic acid, myelosuppression with prolonged use

Drugs of Choice- Pseudomonas Aeruginosa

- Piperacillin/Tazobactam - Cefepime, Ceftazidime - Ceftazidime/Avibactam - Ceftolozane/Tazobactam - Carbapenems (except *Ertapenem*) - Ciprofloxacin, Levofloxacin - Aztreonam - Aminoglycosides - Colistimethate, Polymyxin B

Cell Membrane Inhibitors

- Polymyxins - Daptomycin - Telavancin - Oritavancin

Antistaphylococcal Penicillins- Clinical Pearls

- Preferred for *MSSA* soft tissue, bone and joint, endocarditis, and bloodstream infections. - NO renal dose adjustments - Nafcillin is a *vesicant*, meaning it can cause severe chemical burns, blisters, and pain if extravasated. Administation of Nafcillin is preferably through a central line to avoid this adverse effect. If extravasation occurs, use cold packs and hyaluronidase injections.

DNA/RNA Inhibitors

- Quinolones (through DNA Gyrase or Topoisomerase IV) - Metronidazole, Tinidazole - Rifampin

Polymyxins- Overview

- The Polymyxin class consists of two drugs, Colistimethate (AKA Colistin, or Coly-Mycin M), and Polymyxin B. - Colistimethate (Coly-Mycin M) is an inactive prodrug that is hydrolyzed to Colistin. It acts as a cationic detergent and damages the bacterial cytoplasmic membrane, causing leakage of the intracellular substances and cell death. - Polymyxins cover gram-negative bacteria, such as Enterobacter spp., E Coli, Klebsiella pneumoniae, and Pseudomonas, BUT they do NOT cover Proteus spp. - Due to the risk of toxicities, they are used primarily for MDR Gram-negative pathogens in combination with other antibiotics.

Drugs of Choice- Nosocomial MRSA

- Vancomycin (consider alternative if MIC 2+) - Linezolid - Daptomycin (NOT in pneumonia) - Rifampin (only in select infections, and NEVER used alone) - Telavancin

Drugs of Choice- C. Difficile Infections

- Vancomycin (oral) - Fidaxomicin - Metronidazole - Rifaximin

Vancomycin- Overview

- Vancomycin is a glycopeptide that inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine cell wall precursor and blocking peptidoglycan polymerization. - Vancomycin only covers gram-positive bacteria, including Staphylococci (MRSA), Streptococci, Enterococci (not VRE), and C. Difficile (PO route only). - Vancomycin is FIRST LINE for MRSA infections, BUT, an alternative drug should be considered when the MRSA MIC is 2+ mcg/mL

Monobactams- Drugs, Dosing

1. *Aztreonam (Azactam)* - IV: 500-2,000 mg q6-12hrs - Dose adjustment when CrCl is 30 or less 2. Aztreonam Inhalation (Cayston) - Inhalation: 75 mg TID for 28 days then 28 days off - Inhaled for Cystic Fibrosis - No dose adjustments needed

Aminoglycosides- Drugs

1. *Gentamicin* - IV, IM, Ophthalmic, Topical 2. *Tobramycin* - IV, IM, Ophthalmic - Also available Inhaled (as TOBI, TOBI Podhaler, Bethkis, Kitabis Pak) for Cystic Fibrosis 3. *Amikacin* - IV, IM 4. Streptomycin - IM 5. Plazomicin (Zemdri) - IV (used ONLY in complicated UTI/Pyelonephritis when no other options are available

Acute Otitis Media- Antibiotic Treatments

1. *High-dose Amoxicillin* or *Amoxicillin/Clavulanate* are first-line for AOM. - High-dose Amoxicillin is needed to cover most strains on S. Pneumoniae. - With Augmentin, the formulation with the *least amount of Clavulanate* should be used to decrease the risk of diarrhea. The target Amoxicillin to Clavulanate ratio is *14 to 1*, making Augmentin ES-600 (Amoxicillin 600 mg/Clavulanate 42.9 mg per 5 mL) a common formulation. 2. In children with a non-severe penicillin allergy, the American Academy of Pediatrics (AAP) recommends a Cephalosporin. - Although there is some risk of cross-reactivity, it is low with the 2nd- and 3rd-generation Cephalosporins (Cefuroxime, Cefdinir, Cefpodoxime, and Ceftriaxone). - None beta-lactams that are suitable for use in children, such as Azithromycin, have limited efficacy against the typical pathogens due to resistance. The treatment duration with oral medications is 10 days for children less than 2, 7 days for children 2 to 5, and 5 to 7 days for children 6 and older.

Acute Uncomplicated UTI- Primary Treatment

1. *Nitrofurantoin (Macrobid) 100 mg BID with food for 5 days* - CONTRAINDICATED if CrCl <60 mL/min 2. *SMX/TMP DS 1 Tablet BID for 3 days* - CONTRAINDICATED in sulfa allergies or when E Coli resistance is 20%+ 3. Fosfomycin 3 grams for 1 dose (inferior efficacy, however)

Quinolones- Boxed Warnings

1. *Tendon inflammation and/or rupture*, often the Achilles Tendon, within hours/days or starting or up to several months after completion of treatment. - Increased risk with concurrent use of steroids, in organ transplant patients and those aged >60 years. - Discontinue immediately if symptoms occur. 2. *Peripheral Neuropathy* which can last months to years after the drug has been discontinued, and may become permanent. - Discontinue immediately if symptoms occur. 3. *CNS Effects* such as *seizures*, tremor, restlessness, confusion, hallucinations, depression, suicidal thoughts, paranoia, nightmares, insomnia, and increased intracranial pressure (including pseudotumor cerebri). - Use caution in patients with CNS disorders or with drugs that cause seizures, or lower the seizure threshold. 4. Muscle Weakness- Avoid in patients with Myasthenia Gravis 5. Collateral Damage- Use LAST-LINE (only if no other possible treatments) for: - Acute bacterial sinusitis - Acute exacerbation of chronic bronchitis - Uncomplicated UTI (except Moxifloxacin)

Key Class Effects of Carbapenems

1. ALL cover ESBL-producing organisms 2. All except *Ertapenem* cover Pseudomonas 3. Do not use in patients with penicillin allergies 4. Seizure risk (especially with higher doses, renal failure, or the use of Imipenem/Cilastatin)

Non-severe CAP Antibiotic Treatment

1. Beta-lactam + Macrolide or Doxycycline - Preferred Beta-lactams are *Ceftriaxone, Cefotaxime*, Ceftaroline, or Ampicillin/Sulbactam 2. Respiratory Quinolone Monotherapy - Moxifloxacin, Gemifloxacin, Levofloxacin

Key Class Effects of Penicillins

1. ALL penicillins should be avoided in patients with a beta-lactam allergy --- EXCEPTION: Treatment of syphilis during pregnancy (all patients) and in HIV patients with poor compliance/follow-up. These patients should be *desensitized* and treated with Penicillin G Benzathine. 2. ALL penicillins increase the risk of seizures if accumulation occurs (e.g. with renal failure)

Aminopenicillins

1. Amoxicillin (Moxatag, Amoxil) - Tablet, Capsule, Chewable Tablet, Suspension - PO dosing varies with formulation, 24 hour ER tablet is taken once daily. 2. Amoxicillin/Clavulanate (Augmentin, Augmentin ES-600) - Tablet, Chewable Tablet, Suspension - PO dosing varies with formulation, XR tablet is taken every 12 hours with food 3. Ampicillin - Injection, Capsule, Suspension - PO: 250-500 mg q6h on an empty stomach 1 hour before or 2 hours after meals - IV/IM 1-2 grams q4-6h 4. Ampicillin/Sulbactam (Unasyn) - Injection - IV: 1.5 to 3 grams q6h

Quinolones- Drug Interactions

1. Antacids and Polyvalent Cations - E.G. Magnesium, Aluminum, Calcium, Iron, Zinc - Multivitamins, Sucralfate, Bile Acid Resins - These can chelate and inhibit quinolone absorption, leading to decreased antibiotic concentrations. 2. Lanthanum Carbonate (Fosrenol) and Sevelamer (Renvela) - Can decrease the serum concentration of oral quinolones. - Separate administration by at least two hours before, and at least two hours after (with Lanthanum) or six hours after (with Sevelamer). 3. Warfarin - Quinolones can increase the concentration of warfarin, increasing its effects (increased risk of bleeding) 4. Hypoglycemic Medications - Quinolones can increase the effect of Oral Hypoglycemic Medications, such as Sulfonylureas, Insulin and others (possibly even those that do not affect blood sugar, but can when used with other medications, like metformin, GLP-1RAs, SGLT2i, DPP-4i) 5. QTc Prolongation - Caution with medications that can prolong the QTc (e.g. Azole antifungals, Antipsychotics, Methadone, Macrolides) - Caution in patients with CVD, those with hypokalemia and/or hypomagnesemia 6. PGP Substrates, CYP450s - Ciprofloxacin is a P-glycoprotein substrate, a strong CYP1A2 inhibitor and a weak CYP3A4 inhibitor. - Can increase the levels and effects of Caffeine, Theophylline, and Tizanidine - Ciprofloxacin is CI'd with concurrent use of Tizanidine.

Reasons for Lack of Response

1. Antibiotic factors - Inadequate spectrum and/or dose - Poor tissue perfusion - Drug-drug Interactions - Non-adherence - Inadequate duration of treatment 2. Microbiologic factors - Resistance - Superinfection (C Difficile) - Alternative etiology (viral, fungal, non-infectious cause) 3. Host factors - Uncontrolled source of infection (e.g. abscess or fluid collection) - Immunocompromised

Lipoglycopeptides- Drug Interactions

1. Avoid Telavancin in patients with Congenital Long QT Syndrome, known QT Prolongation, or uncompensated heart failure. Use caution with other medications known to prolong the QT Interval. 2. Oritavancin is a weak inhibitor of CYP2C9 and 2C19, plus a weak inducer of CYP3A4 and 2D6, so use with caution when coadministered with drugs metabolized by these enzymes (including Warfarin).

Key Counseling Points- Tetracyclines

1. Avoid in pregnancy, breastfeeding, and children under 8 years old 2. Drug interactions due to binding 3. Can cause photosensitivity 4. Doxycycline-specific - Take with a full glass of water and remain upright for 30 minutes after the dose to avoid GI irritation.

Key Counseling Points- Bactrim

1. Avoid in: - Pregnancy or breastfeeding - Sulfa allergy 2. Can cause: - Photosensitivity - Crystals in urine. Take with a full glass of water

Macrolides- Drugs and Dosing

1. Azithromycin (Zithromax, Z-Pak, Tri-Pak, AzaSite eye drops) - Tablets, suspension, injection, ophthalmic - *Z-Pak: 500 mg on day 1, then 250 mg on days 2-5* - *Tri-Pak: 500 mg daily for 3 days* - IV: 250-500 mg QD - Dosing regimens vary depending on the indication - No dose adjustment in renal impairment 2. Clarithromycin (Biaxin, Biaxin XL) - Tablets, suspension - PO: 250-500 mg every 12 hours or 1 gram (ER) daily - CrCl <30, dose adjustment required 3. Erythromycin (E.E.S., Ery-Tab, Erythrocin, EryPed, Ery and Erygel topical) - Capsule, tablet, suspension, injection, ophthalmic, topical - Dosing varies by product, however, EES 400 mg = 250 mg of Erythromycin base or stearate - Erythromycin Lactobionate is the IV form - No dose adjustment in renal impairment

Severe CAP Antibiotic Treatment

1. Beta-lactam + Macrolide 2. Beta-lactam + Respiratory Quinolone (DO NOT USE QUINOLONE MONOTHERAPY)

Sulfonamide Antibiotics- Warnings, Monitoring

1. Blood dyscrasias, including agranulocytosis and aplastic anemia (due to folic acid synthesis inhibition) 2. Skin reactions like SJS/TEN/DRESS, and Thrombotic Thrombocytopenic Purpura (TTP) 3. G6PD Deficiency: DO NOT USE WITH KNOWN DEFICIENCY and discontinue if hemolysis occurs 4. Hypoglycemia 5. Thrombocytopenia Monitoring - Renal Function - Electrolytes - CBC - Folate levels

Oxazolidinones- Drug Interactions

1. Both Linezolid and Tedizolid are reversible Monoamine Oxidase Inhibitors (Linezolid is CI with or within two weeks of an MAOI, Tedizolid is NOT). - Avoid Tyramine-containing foods and serotonergic medications while on these medications 2. Linezolid can exacerbate hypoglycemic episodes, so use with caution in patients receiving insulin or oral hypoglycemic medications (such as Sulfonylureas)

Carbapenems- Drug Interactions

1. Carbapenems can decrease the serum concentration of *valproic acid*, leading to a loss of seizure control 2. Use with caution in patients at risk for seizures, or in combination with other medications known to lower the seizure threshold. Examples include: - Ganciclovir - Quinolones - Bupropion - Tramadol

Key Inpatient Cephalosporins

1. Cefazolin - Commonly used for surgery prophylaxis 2. Cefotetan or Cefoxitin - Used for anaerobic coverage (B. fragilis) - Commonly used for surgical prophylaxis in colorectal procedures - *cefotetan can cause a disulfiram-like reaction with alcohol ingestion* 3. Ceftriaxone and Cefotaxime - Commonly used for CAP, meningitis, spontaneous bacterial peritonitis (SBP), pyelonephritis - Ceftriaxone has no renal dose adjustments BUT should *not* be used in neonates (age 0-28 days). 4. Ceftazidime and Cefepime - These have activity against Pseudomonas 5. Ceftolozane/Tazobactam and Ceftazidime/Avibactam - Used for MDR gram-negative organisms (including Pseudomonas) 6. Ceftaroline - ONLY beta-lactam active against MRSA

First Generation Cephalosporins- Drugs, Dosing

1. Cefazolin (Ancef) - IV/IM 1-1.5 grams q8hrs 2. Cephalexin (Keflex) - *PO 250-500 mg q6-12hrs* 3. Cefadroxil - PO 1-2 grams q12-24hrs

Perioperative Antibiotic Selection

1. Cefazolin, a first-generation cephalosporin, or Cefuroxime, a second-generation cephalosporin, is *preferred* for most surgeries to prevent methicillin-susceptible Staphylococcus aureus and Streptococci infections. 2. Clindamycin is an alternative if the patient has a documented beta-lactam allergy. 3. In colorectal surgeries, the prophylactic antibiotic regimen needs to cover skin flora plus broad-spectrum gram-negative and anaerobic organisms found in the gut. 4. Vancomycin should be included in the regimen if MRSA colonization or risk is present. Vancomycin is an alternative if the patient has a beta-lactam allergy and cannot take Clindamycin.

Third Generation Cephalosporins Group #1- Drugs, Dosing

1. Cefdinir (Omnicef) - PO 300 mg q12hrs or 600 mg daily 2. Ceftriaxone (Rocephin) - IV/IM 1-2 grams q12-24hrs 3. Cefotaxime - IV/IM 1-2 grams q4-12hours 4. Cefditoren (Spectracef) - PO 200-400 mg q12hrs with food 5. Cefixime (Suprax) - PO 400 mg divided q12-24hrs 6. Cefpodoxime - PO 100-400 q12hrs 7. Ceftibuten - PO 400 mg daily on an empty stomach

Fourth Generation Cephalosporins- Drugs, Dosing

1. Cefepime (Maxipime) - *IV/IM 1-2 grams q8-12hrs*

Siderophore Cephalosporins- Drugs, Dosing

1. Cefiderocol (Fetroja) - IV 2 grams q8hrs

Fifth Generation Cephalosporins- Drugs, Dosing

1. Ceftaroline Fosamil (Teflaro) - IV 600 mg q12hrs

Third Generation Cephalosporins Group #2- Drugs, Dosing

1. Ceftazidime (Fortaz, Tazicef) - IV/IM 1-2 grams q8-12hrs 2. Ceftazidime/Avibactam (Avycaz) - IV 2.5 grams q8hrs 3. Ceftolozane/Tazobactam (Zerbaxa) - IV 1.5 grams q8hrs

Second Generation Cephalosporins- Drugs, Dosing

1. Cefuroxime (Ceftin) - *PO/IV/IM 250-1,500 mg q8-12hrs* 2. Cefotetan (Cefotan) - *IV/IM 1-2 grams q12hrs* 3. Cefaclor - PO 250-500 mg q8hrs 4. Cefoxitin - IV/IM 1-2 grams q6-8hrs 5. Cefprozil - PO 250-500 mg q12-24hrs

Key Outpatient Cephalosporins

1. Cephalexin (Keflex) - Commonly used for skin infections (MSSA) and strep throat 2. Cefuroxime - Commonly used for acute otitis media, community-acquired pneumonia (CAP), and sinus infections (if antibiotics are indicated). 3. Cefdinir - Commonly used for CAP and sinus infections (if antibiotics are indicated).

Tetracyclines- Warnings

1. Children < 8 years of age, pregnancy and breastfeeding: - Suppresses bone growth and skeletal development, and permanently discolors teeth 2. Photosensitivity, Tissue hyperpigmentation, Severe skin reactions (SJS/TEN/DRESS), Exfoliative dermatitis 3. Minocycline: Drug-Induced Lupus Erythematosus (DILE)

Sexually Transmitted Infections- Common Symptoms

1. Chlamydia - Genital discharge or no symptoms 2. Gonorrhea - Genital discharge or no symptoms 3. Syphilis - Painless, smooth genital sores (called chancres) 4. HPV - Genital warts or no symptoms 5. Bacterial Vaginosis (females only) - Vaginal discharge that is clear, white or gray with a "fishy" odor and a pH of >4.5. There is little to no pain. 6. Trichomoniasis - Yellow/green frothy vaginal discharge with soreness/pain with intercourse

Macrolides- Warnings

1. QT Prolongation - Highest risk with Erythromycin - Avoid in patients with known QT Prolongation, or those with additive risks, such as hypokalemia, use of other drugs that prolong the QT interval (including Class Ia and Class III antiarrhythmics). 2. Hepatotoxicity - Use with caution in patients with liver disease 3. Exacerbation of Myasthenia Gravis 4. Clarithromycin ONLY: Use with caution in patients with Coronary Artery Disease. - Increased mortality has been documented at 1+ years after the end of a 2-week course of treatment

HAP/VAP- Selecting an Empiric Regimen

1. Choose ONE antibiotic to cover Pseudomonas and MSSA if the patient is LOW RISK for MRSA or MDR pathogens. Examples include: - Cefepime - Piperacillin/Tazobactam 2. Choose TWO antibiotics, one for MRSA and one for Pseudomonas if the patient has a risk for MRSA (positive MRSA nasal swab), but low risk for MDR pathogens. Examples include: - Cefepime + Vancomycin - Meropenem + Linezolid 3. Choose THREE antibiotics, one for MRSA and TWO for Pseudomonas if the patient has a risk for both MRSA and MDR pathogens (e.g. IV antibiotics within the past 90 days). Examples include: - Piperacillin/Tazobactam, Ciprofloxacin and Vancomycin - Cefepime, Gentamicin, and Linezolid

Quinolones- Drugs and Dosing

1. Ciprofloxacin - PO: 250-750 mg q12hrs - IV: 200-400 mg q8-12hrs - CrCl 30-50 mL/min: q12hrs - CrCl <30 mL/min: q18-24hrs 2. Levofloxacin - PO/IV: 250-750 mg q24hrs - CrCl <50 mL/min: Extended-dosing interval (q48hrs and/or lower the dose. Adjustment varies based on the indication and the renal function. 3. Moxifloxacin - IV/PO: 400 mg q24hrs - *No dose adjustment in renal impairment* 4. Delafloxacin - PO: 450 mg q12hrs - IV: 300 mg q12hrs - CrCl 15-29: Dose adjustment needed for *IV only* - CrCl <15 mL/min: Do not use (PO or IV) 5. Gatifloxacin - No oral formulation 6. Gemifloxacin - PO: 320 mg q24hrs - CrCl 40 or less: dose adjustment required 7. Ofloxacin - PO: 200-400 mg q12hrs - CrCl <30 mL/min: dose adjustment required

Miscellaneous Antibiotics

1. Clindamycin (Cleocin) 2. Metronidazoles - Metronidazole (Flagyl, Metro-) - Tinidazole (Tindamax) - Secnidazole (Solosec) 3. Lefamulin (Xenleta) 4. Fidaxomicin (Dificid) 5. Rifaximin (Xifaxan)

Urinary Tract Infections- Symptoms

1. Cystitis (lower UTI) - *Urgency and frequency*, which is the feeling of needing to go often and quickly, including overnight (*Nocturia*). - *Dysuria*, which is painful/burning urination. - *Suprapubic heaviness* - *Hematuria*, which is blood in the urine 2. Pyelonephritis (Upper UTI) - *Flank pain* or costovertebral angle pain - Abdominal pain, nausea, vomiting - Fevere and malaise Often UTIs are confused with Vaginal Candida Albicans, which is a yeast infection in females. Symptoms of a yeast infection are: - Extremely *itchy* - White, thick, cottage cheese-like discharge

Antibiotic Mechanisms of Action

1. DNA/RNA Inhibitors 2. Cell Membrane Inhibitors 3. Protein Synthesis Inhibitors 4. Cell Wall Inhibitors 5. Folic Acid Synthesis Inhibitors

Antistaphylococcal Penicillins

1. Dicloxacillin - Capsule - PO: 125 to 500 mg q6h 2. Nafcillin - Injection - IV/IM: 1 to 2 grams q4-6h 3. Oxacillin - Injection - IV: 250 to 2,000 mg q4-6h

Key Counseling Points- Metronidazole

1. Do not use any alcohol products while using this medication, and AT LEAST for 3 DAYS afterwards 2. Can cause: - Nausea - Metallic taste in mouth

Carbapenems- Drugs and Dosing

1. Doripenem - IV: 500 mg q8hrs - Renal adjustment needed when CrCl 50 or less 2. Imipenem/Cilastatin (Primaxin I.V.) - IV: 250-1,000 mg q6-8hrs - Dose adjustment when CrCl 90 or less 3. Imipenem/Cilastatin/Relebactam (Recarbio) - IV: 1.25 mg q6hrs - Dose adjustment when CrCl 90 or less 4. *Meropenem (Merrem)* - IV: 500-1,000 mg q8hrs - Dose adjustment when CrCl 50 or less 5. Meropenem/Vaborbactam (Vabomere) - IV: 4 grams q8hrs - Dose adjustment when CrCl 50 or less 6. *Ertapenem (Invanz)* - IV/IM: 1 gram QD - Dose adjustment when CrCl 30 or less - *Stable in NS only*

Tetracyclines- Drugs and Dosing

1. Doxycycline - PO/IV: 100-200 mg daily in 1-2 divided doses - Take with food to decrease GI irritation (except for Oracea). - Take Oracea on an empty stomach, 1 hr before or 2 hrs after meals. - NO DOSE ADJUSTMENT IN RENAL IMPAIRMENT 2. Minocycline - PO/IV: 200 mg x once then 50-100 mg q12hrs - CrCl <80: MAX of 200 mg daily 3. Eracacycline - IV: 1 mg/kg q12hrs - Only approved for complicated intra-abdominal infections 4. Omadacycline - Dose is based on indication (FDA approved only for CAP and skin infections) 5. Sarecycline - Dose based on body weight, approved for moderate-severe acne vulgaris 6. Tetracycline - PO: 250-500 mg q6hrs on an empty stomach - CrCl <50: Dose adjustment required

Tetracyclines- Drugs

1. Doxycycline - Vibramycin, Doryx, Morgidox, Oracea, Acticlate, and others. - Capsule, suspension, tablet, syrup, injection 2. Minocycline - Minocin, Solodyn, CoreMino, Ximino - Capsule, tablet, injection 3. Eravacycline - Xerava - Injection 4. Omadacycline - Nuzyra - Tablet, injection 5. Sarecycline - Seysara - Tablet 6. Tetracycline - Capsule

Key Features of Cephalosporins

1. Due to a small risk of cross-sensitivity (<10%), *do not choose* a cephalosporin if the patient has a penicillin allergy (exception: pediatric patients with acute otitis media). 2. Risk of seizures if accumulation occurs (e.g. with renal failure)

Antibiotic Sequence in the Hospital

1. Empiric Treatment - Select the empiric treatment based on the likely organisms at the infection site. Things to consider includes MRSA, Pseudomonas, Multi-Drug Resistant bacteria risk factors. If these are present, provide coverage of those. Use the antibiogram and gram-stain (if available) to guide antibiotic selection. 2. Streamline - When the C&S is available, streamline to narrow-spectrum antibiotics ASAP. If >1 organism is present, try to find one antibiotic that will treat both. - Consider IV:PO conversion if the patient is eating normally and there is an appropriate oral medication that can be used for the infection. 3. Assess the patient - Throughout treatment the patient should be monitored for improvement. The patient's condition can override the culture information. It is possible that the ID'd organism is not causing the illness! Set a standard duration of treatment for each antibiotic and do not let the antibiotics continue until discharge unless absolutely necessary.

Telavancin- Boxed Warnings

1. Fetal toxicity - Obtain a pregnancy test prior to starting therapy 2. Nephrotoxicity 3. Increased mortality in Moderate-Severe Renal Impairment - Increased mortality seen in pre-existing moderate to severe renal impairment (CrCl 50 or less) when compared to Vancomycin in pneumonia trials.

Urinary Antibiotics

1. Fosfomycin (Monurol) 2. Nitrofurantoin (Macrobid, Macrodantin, Furadantin)

Latent TB Treatment- Alternative Regimens

1. INH 300mg daily for 6 or 9 months - This is an alternative regimen for HIV-negative or positive patients, adults and children of all ages. - This may be preferred in HIV-positive patients at risk for drug interactions with rifampin- or rifapentine-based regimens. - INH for 9 months is *treatment of choice* in pregnant women.

Latent TB Treatment- Preferred Regimens

1. INH and Rifapentine once WEEKLY for 12 weeks via Directly Observed Therapy (DOT), or self-administered. - This regimen is strongly recommended in adults, children >2 years old, and HIV positive patients (if no drug interactions with antiretroviral therapy [ART]). - DO NOT use this regimen in pregnant women 2. Rifampin 600mg daily for 4 months. - This is a preferred regimen in children of all ages and HIV-negative adults. - However, drug interactions are the biggest barrier to use. 3. Isoniazid with Rifampin for 3 months. - Can be used in adults, children and HIV-positive patients, if no DDIs with ART exist.

Nitrofurantoin- Dosing and Administration

1. Macrodantin - Active infection: 50-100 mg PO QID for 3 to 7 days - Prophylaxis: 50-100 mg PO QHS 2. Macrobid - 100 mg BID for 5 days Nitrofurantoin is available as a capsule and suspension. The macrocrystal formulation, Macrobid, dissolves more slowly and is given twice a day. Regardless of formulation, patients should take Nitrofurantoin with food to prevent nausea or stomach cramping. The medication can also discolor the urine brown, which is very important to counsel on.

Metronidazoles- Dosing and Administration

1. Metronidazole - PO/IV: 500-750 mg every 8 to 12 hours or 250-500 mg every 6 to 8 hours - Take immediate-release tablets with food to decrease GI upset - No dose adjustments in renal impairment - IV to PO ratio is 1 to 1 2. Tinidazole - PO: 2 grams by mouth daily - Take with food to minimize GI effects 3. Secnidazole - PO: 2 grams by mouth as a SINGLE DOSE - Sprinkle contents of 1 packet onto applesauce, yogurt, or pudding and consume within 30 minutes. Do not chew the granules.

Metronidazoles- Medications

1. Metronidazole (Flagyl, Metro-) - Available as a tablet, capsule, injection, a topical, and a vaginal insert 2. Tinidazole (Tindamax) - Available as a tablet 3. Secnidazole (Solosec) - Available as a granule packet

Key Points for RIPE Therapy for TB

1. Monitor infection - Sputum sample (for culture), symptoms, and chest x-ray (are lungs clear, or clearing up). 2. Drug Specific Key Points - ALL RIPE DRUGS: Increase in LFTs, including Total Bilirubin, monitor accordingly - Rifampin: Orange bodily secretions, Strong CYP450 inducer (use Rifabutin if there are unacceptable DDIs), Flu-like symptoms - Isoniazid: Peripheral neuropathy (give with Pyridoxine 25-50 mg PO daily), monitor for symptoms of DILE - Pyrazinamide: Increased uric acid (do not use with acute gout) - Ethambutol: Visual damage (requires baseline and monthly vision exams), confusion, hallucination

Daptomycin- Warnings

1. Myopathy and Rhabdomyolysis - Discontinue Daptomycin in patients with signs and symptoms of myopathy or Rhabdomyolysis and CPK levels >1,000 units/L (5x the ULN), OR in asymptomatic patients with a CPK level of 2000 or more (10x the ULN). - Consider temporarily withholding other medications that can cause muscle damage during treatment (such as statins). 2. Increased coagulation tests - Daptomycin can *falsely* elevate PT/INR, but there is no increased bleeding risk 3. Peripheral Neuropathy 4. Eosinophilic Pneumonia - Generally develops 2-4 weeks after treatment initiation

Vancomycin- Drug Interactions

1. Nephrotoxic medications (including but not limited to): - Aminoglycosides - Amphotericin B - Cisplatin - Polymyxins - Cyclosporine - Tacrolimus - Loop diuretics - NSAIDs - Radiographic contrast dye 2. Ototoxic medications (including but not limited to): - Aminoglycosides - Cisplatin - Loop diuretics

Influenza- Treatment

1. Oseltamivir x 5 days 2. Baloxavir Marboxil x 1 dose 3. Zanamivir inhalation x 5 days 4. Peramivir (IV) x 1 dose

Vancomycin- Warnings

1. Ototoxicity and Nephrotoxicity - Use caution when used with other nephrotoxic or ototoxic medications, or in prolonged use with high serum concentrations - Dose adjustments are needed in renal impairment (IV ONLY) 2. PO vs IV use - PO use is ONLY for C Difficile infections OR enterocolitis, NOT for systemic infections 3. Red Man Syndrome - Vancomycin can cause a systemic infusion reaction called Red Man Syndrome if given too rapidly - Characteristics include maculopapular rash, hypotension, flushing, and chills - DO NOT INFUSE FASTER THAN 1 GRAM PER HOUR

Penicillins Drug of Choice, Inpatient

1. Penicillin G Benzathine (Bicillin L-A) - Drug of choice for Syphilis (2.4 million units IM ONCE) - NOT for IV use, can cause *death* 2. Nafcillin - Covers MSSA only (NOT MRSA) - No renal dose adjustment needed 3. Piperacillin/Tazobactam - ONLY penicillin active against Pseudomonas - Extended infusions (4 hours) can be used to maximize time above MIC.

Natural Penicillins, Drugs, Formulations, Dosing

1. Penicillin V Potassium (Pen VK) - Tablet, Suspension - 125-500 mg q6-12h on an empty stomach 2. Penicillin G Aqueous (Pfizerpen-G) - Injection - IV 2-4 million units q4-6h 3. Penicillin G Benzathine (Bicillin L-A) - Injection - IM 1.2 to 2.4 million units once (frequency varies) 4. Penicillin G Benzathine and Penicillin G Procaine (Bicillin C-R) - Injection - IM 1.2 to 2.4 million units once (frequency varies)

Penicillin Drug of Choices, Outpatient

1. Penicillin VK - A first-line treatment for strep throat and mild non-purulent skin infections (no abscess) 2. Amoxicillin - First-line treatment for Acute Otitis Media (80-90 mg/kg/day) - Drug of Choice for Infective Endocarditis prophylaxis before dental procedures (2 grams PO one time, 30-60 minutes before the procedure). - Used in H Pylori treatment 3. Amoxicillin/Clavulanate - First-line treatment for Acute Otitis Media (90 mg/kg/day Amoxicillin component), and for sinus infections (if antibiotics are indicated) - Use the LOWEST dose of clavulanate to decrease diarrhea 4. Dicloxacillin and Oxacillin - Covers MSSA only (NO MRSA) - No renal adjustment needed

Extended-Spectrum Penicillins and Clinical Pearls

1. Piperacillin/Tazobactam (Zosyn) - Injection - IV: 3.375 grams q6h - IV: 4.5 grams q6-8h - IV Prolonged/Extended Infusion: 3.375-4.5 grams q8h, each dose infused over 4 hours. Piperacillin/Tazobactam contains 65 mg of Na per 1 gram of Piperacillin.

Key Common Uses for Carbapenems

1. Polymicrobial infections - E.g. moderate-severe diabetic foot infections 2. Empiric therapy when resistant organisms are suspected 3. Resistant Pseudomonas or Acinetobacter (except *Ertapenem*) 4. Ertapenem must be diluted in NORMAL SALINE

Additional Broad-Spectrum Antibiotics

1. Polymyxins - Colistimethate sodium - Polymyxin B sulfate 2. Chloramphenicol

Penicillin Drug Interactions

1. Probenecid - Can increase the levels of beta-lactams by interfering with renal excretion. This combination is sometimes used intentionally in severe infections to increase antibiotic levels. 2. Warfarin - Beta-lactams (except for Nafcillin and Dicloxacillin) can enhance the anticoagulant effect of warfarin by inhibiting the production of vitamin K-dependent clotting factors (Factors II, VII, IX, X and Proteins C and S). 3. Antimetabolites - Penicillins can *increase* the serum concentration of Methotrexate - Penicillins can *decrease* the serum concentration of Mycophenylate active metabolites due to impaired enterohepatic recirculation

Key Counseling Points- All Antibiotics

1. Proper storage (refrigeration or room temperature) and administration (w/ or w/out food) is essential! 2. Shake suspensions well before administration. 3. Antibiotics treat bacterial infections ONLY! They do not treat viral infections, such as the common cold. 4. Complete the full course of therapy, EVEN if symptoms improve. 5. Measure the liquid doses carefully using a measuring device/syringe that comes with the medication. DO NOT USE HOUSEHOLD SPOONS. 6. Some oral liquid and chewable dosage forms contain Phenylalanine. Do not use if you have phenylketonuria (PKU). 7. All antibiotics have the chance to cause: - Rash - Nausea - Diarrhea, including Clostridium Difficile-associated diarrhea. This type of diarrhea typically is accompanied by abdominal pain, cramps, and watery/bloody stool.

Key Counseling Points- Quinolones

1. Quinolones can cause: - CNS effects, including seizures - Hypo/hyperglycemia - Peripheral neuropathy - Photosensitivity - QT prolongation - Tendon inflammation (tendinitis), or tendon rupture. This can present with a "pop" or pain/swelling in the back of the ankle (Achilles), shoulder or hand. 2. Avoid these in pregnancy. 3. There have many drug interactions due to binding. 4. Avoid consuming calcium-rich foods (dairy products) with the dose of antibiotic.

Vancomycin- Monitoring

1. Renal function 2. AUC/MIC ratio or trough levels, serum concentration at steady state (generally 30 minutes before the 4th or 5th dose) - Serious MRSA infections such as bacteremia, sepsis, endocarditis, pneumonia, osteomyelitis, and meningitis should have an AUC/MIC ratio target of 400-600, or a goal trough of 15-20 mcg/mL - Other infections (e.g. UTIs, SSTIs) should have a target trough of 10-15 mcg/mL 3. WBC levels (due to neutropenia/thrombocytopenia)

SMX/TMP Drug Interactions

1. SMX/TMP is a moderate-strong CYP2C8 and 2C9 and can cause a significantly increased INR. Caution should be used when in combination with Warfarin 2. SMX/TMP levels can be reduced by CYP2C8 and 2C9 inducers 3. The therapeutic effects of SMX/TMP can de diminished by the use of Leucovorin or Levoleucovorin 4. The risk of hyperkalemia will be increased if used in combination with ACE Inhibitors, ARBs, Aliskiren, Aldosterone Antagonists, Potassium-Sparing Diuretics, NSAIDs, Cyclosporine, Tacrolimus, Drospirenone-containing oral contraceptives (related to potassium-sparing diuretics and aldosterone antagonists), or Canagliflozin

Sulfonamide Antibiotics- Key Features

1. SMX/TMP is most commonly used for CA-MRSA infections, UTIs, and Pneumocystis Pneumonia (PCP) 2. The dosing of SMX/TMP is in a *5 to 1 ratio (SMX to TMP)* and SMX/TMP is dosed using the *TMP* component - Single Strength tablets have 80 mg of TMP - Double Strength tablets have 160 mg of TMP 3. SULFA ALLERGY - Most sulfa allergies occur with SMX/TMP, with rashes and hives being the most common reaction - Rarely, severe skin reactions (SJS/TEN) can occur - If a rash is accompanied by a fever or systemic symptoms, seek emergency care immediately! 4. Drug Interactions - INR is increased with Warfarin! Use an alternative antibiotic if possible

Sulfonamide Antibiotics- Contraindications

1. Sulfa allergy 2. Pregnancy (at term) and breastfeeding: - Blocks folic acid synthesis, leading to congenital defects 3. Anemia due to folic acid deficiency 4. Renal or hepatic disease 5. Infants <2 months of age

Sulfonamide Antibiotics- Drugs

1. Sulfamethoxazole/Trimethoprim (SMX/TMP) - Bactrim, Bactrim DS, Sulfatrim Pediatric, others - Available as a Single Strength tablet, Double Strength tablet, suspension, and injection - Single Strength: 400 mg SMX/80 mg TMP - Double Strength: 800 mg SMX/160 mg TMP

SSTI Classifications

1. Superficial - Impetigo - Furuncles - Carbuncles 2. Nonpurulent - Cellulitis 3. Purulent - Abscesses Each is further divided into mild, moderate, and severe: - Mild: Systemic signs are absent - Moderate: Systemic signs are present (Temperature >100.4, Heart rate >90, WBC >12,000 OR <4,000) - Severe: Failed oral antibiotics PLUS incision and drainage (if purulent), systemic signs are present, there are signs of a deeper infection (fluid-filled blisters, skin sloughing, hypotension, or evidence of organ dysfunction) or the patient is immunocompromised.

Key Counseling Points- Nitrofurantoin

1. Take with food to decrease nausea 2. Can cause: - Nausea - Brown discoloration of urine (temporary and harmless)

Lipoglycopeptides- Clinical Considerations

1. Telavancin - Approved for complicated skin and soft-tissue infections, and hospital-acquired and ventilator-associated pneumonia 2. Oritavancin and Dalbavancin - Extremely long half-life allows for a *single-dose* regimen for both - Both are approved only for SSTI - If osteomyelitis is suspected or confirmed, switch from Oritavancin to something else

Lipoglycopeptides- Drugs

1. Telavancin (Vibativ) 2. Oritavancin (Orbactiv) 3. Dalbavancin (Dalvance)

Lipoglycopeptides- Drug Dosing

1. Telavancin (Vibativ) - IV: 10 mg/kg daily, infuse over 60 minutes to prevent infusion reaction - CrCl 50 or less: Dose adjustment required 2. Oritavancin (Orbactiv) - IV: SINGLE DOSE OF 1,200 MG, infuse over 3 hours - CrCl <30: Not studied, use with caution 3. Dalbavancin (Dalvance) - IV: SINGLE DOSE OF 1,500 MG - IV: TWO-DOSE REGIMEN OF 1,000 mg once, then 500 mg one week later - Infuse over 30 minutes - CrCl <30 (NOT on dialysis): Dose adjustment required

Rifaximin- Dosing and Administration

1. Travelers' Diarrhea - PO: 200 mg three times a day for 3 days 2. Decrease Hepatic Encephalopathy recurrence - PO: 550 mg twice a day 3. IBS-D - PO: 550 mg three times a day for 14 days Rifaximin (Xifaxan) is only available as a tablet.

Acute Otitis Media- Antibiotic Treatment Decision

1. Try observation for 2 to 3 days if symptoms are non-severe (mild otalgia <48 hours or temperature <102.2) AND: - Age 6-23 months: symptoms in ONE ear only - Age 2+ years: symptoms in one or both ears 2. If symptoms do NOT improve or worsen after 72 hours, use antibiotics. Typically, however, a prescription for antibiotics will be filled and started in the child immediately if the parent gets one and told to observe first.

Antibiotics for Gram-Positive Injections

1. Vancomycin 2. Lipoglycopeptides 3. Daptomycin 4. Oxazolidinones 5. Quinupristin/Dalfopristin 6. Tigecycline

Infective Endocarditis- Organisms and Treatment

1. Viridians group Streptococci - Penicillin or Ceftriaxone (+/- Gentamicin) - If beta-lactam allergy, use Vancomycin monotherapy 2. Staphylococci (MSSA) - Nafcillin or Cefazolin (+ Gentamicin and Rifampin if prosthetic valve) - If beta-lactam allergy, use Vancomycin (+ Gentamicin and Rifampin if prosthetic valve) - Daptomycin monotherapy is an alternative for MSSA and MRSA IE when the patient has a beta-lactam allergy and no prosthetic valve 3. Staphylococci (MRSA) - Vancomycin (+ Gentamicin and Rifampin if prosthetic valve) - Daptomycin monotherapy is an alternative for MSSA and MRSA IE when the patient has a beta-lactam allergy and no prosthetic valve 4. Enterococci - Penicillin or Ampicillin + Gentamicin (for both native and prosthetic valve IE) - If beta-lactam allergy, use Vancomycin + Gentamicin - If VRE, use Daptomycin or Linezolid

Abscess/Purulent Infections- Treatment

A single abscess with no systemic signs or symptoms (AKA mild infections) are primarily treated with just incision and drainage (I&D). If there are systemic signs or multiple sites of infection (AKA moderate infections), I&D should be performed, the fluid should be cultures, and antibiotics that cover CA-MRSA should be given. These include: - *SMX/TMP* DS 1-2 tablets PO BID - *Doxycycline 100mg* PO BID - Minocycline 200mg PO x 1, then 100mg PO BID - Clindamycin 300mg PO QID - Linezolid may be used, but it is more expensive. If the culture shows MSSA, used Cephalexin.

Acute Uncomplicated UTI- Overview, Bacteria

AKA Acute Uncomplicated Cystitis, this type of UTI is in females of child-bearing age and are non-pregnant. Common pathogens include: - E coli (vast majority) - Klebsiella - S saprophyticus - Enterococci These are typically treated empirically as an outpatient. If there is no response with first-line treatment, patients will get a urine culture and treat accordingly.

Clostridium Difficile Infection- Overview

AKA Clostridioides Difficile Infection, or C. Diff, is an infection of the GI tract of a gram-positive, obligate anaerobic, spore-forming rod. The GI tract contains >1,000 species of organisms as part of the normal flora, and antibiotics can eliminate much of the "healthy" bacteria, allowing for an overgrowth of C difficile. Some types of C difficile release toxins (*toxins A and B*) that attack the intestinal lining, causing inflammation of the colon (colitis). Symptoms of C Diff infection (CDI) include: - Abdominal cramps - Profuse diarrhea (can be bloody) - Fever Inflammation of the colon can lead to *Pseudomembranous colitis*, which can progress to toxic megacolon, resulting in a colectomy to treat, or death if left untreated. Rates of CDI have increased in recent years due to the overuse of antibiotics. Other risk factors include: - Recent healthcare exposure - Use of PPIs - Advanced age - Immunocompromised state - Obesity - Previous CDI

Key Organisms Carbapenems DON'T COVER

ALL CARBAPENEMS - Atypicals, VRE, MRSA, C Difficile, Stenotrophomonas ERTAPENEM - Pseudomonas, Acinetobacter, or Enterococcus - EAP doesn't cover EAP

Abscess/Purulent Infections- Presentation and Bacteria

Abscesses are areas of infection that initially appear as a fluid collection that is large, red, and may leak pus. These can be recurrent and require more attention to treatment than the other skin infections. Abscesses are typically caused by MRSA, and are extremely contagious. To avoid spreading, the patient should keep the lesion covered, do not share any personal towels, and they should wash their sheets/towels/clothing in hot water. Recurrent MRSA infections should be treated by a nasal decolonization with nasal Mupirocin, and skin decolonization with Chlorhexidine or dilute bleach.

Active TB Diagnosis

Active TB is a public health issue because it is HIGHLY contagious and can be very difficult to treat. A positive TST test is likely with active TB, but the diagnosis *must be confirmed* with a sputum culture. M tuberculosis (MTB) is an acid-fast bacilli and can be detected using an AFB strain in the laboratory. The acid-fast stain is not specific for MTB, and a definitive diagnosis must be made using PCR testing or culture results. MTB is a slow-growing organism, so the final culture and susceptibility results can take up to 6 weeks.

Active TB Treatment Overview

Active TB treatment is divided into two phases, Intensive and Continuation. To avoid resistance, the preferred Intensive phase regimen consists of FOUR drugs: *Rifampin, Isoniazid, Pyrazinamide, and Ethambutol* (RIPE) for TWO months. After two months of RIPE therapy, the Continuation phase, typically lasting for 4 months, consists of scaled back therapy with only TWO drugs (commonly Rifampin and Isoniazid) depending on the drug susceptibility of the isolate. This phase's duration can be increased to seven months in select cases, such as the sputum culture remaining positive after two months of treatment, or the intensive phase treatment did NOT include Pyrazinamide. DOT is used to increase medication adherence, and is preferred in select populations (homeless, MDR disease, adherence issues, positive sputum smears, and delayed culture positivity). Alternative dosing regimens, 2-3x per week, may also be used in this setting. If DOT is not possible, daily dosing regimens are strongly encouraged.

Acute Otitis Media- Overview

Acute Otitis Media (AOM) is the most common childhood infection in the United States that requires antibiotic treatment. Signs and symptoms often have a rapid onset and can include: - Bulging tympanic membrane (eardrums) - Otorrhea (middle ear effusion/fluid) - Otalgia (ear pain) - Fever - Crying - Tugging or rubbing in the ears Treatment involves systemic medications for the pain (such as Acetaminophen or Ibuprofen) rather than topical anesthetic drugs. As most AOM is viral, antibiotics will be ineffective, HOWEVER, some AOM is caused by bacteria, and therefore antibiotics may be indicated. Because of this AOM is first typically treated with Observation without antibiotics for 48-72 hours if the AOM is non-severe. This is also dependent on age and the extent of the infection. Severe symptoms include - Moderate to severe otalgia for >48 hours OR - Temperature >102.2

Acute Bacterial Exacerbation of Chronic Bronchitis

Acute bacterial exacerbation of chronic bronchitis (ABECB) is primarily due to COPD, which is often diagnosed in older patients who smoke (or have a long history or smoking). ABECB can also be referred to as a *COPD Exacerbation*. It can flare repeatedly, which impacts quality of life for the patient. Most exacerbations are triggered by infections, either bacterial or viral, pollution, pulmonary embolism, or some other unknown cause. ABECB is diagnosed based on the presentation. The GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease) defines an acute exacerbation as an *acute increase in symptoms* (e.g. dyspnea, increased sputum production or purulence, cough or wheeze) beyond the normal day-to-day variation, that necessitates a change in COPD medications. Supportive treatment is often adequate, but antibiotics should be given for 5 to 7 days in *select patients*.

Acute Uncomplicated Pyelonephritis- Overview, Bacteria

Acute pyelonephritis is a more severe form of UTI where the bacteria has infected part of the kidney, causing systemic symptoms. It is essentially treated the same way as an acute uncomplicated UTI if the patient meets criteria for uncomplicated infections. Common bacteria are essentially the same as well with one exception: Pseudomonas. The common bacteria include: - E Coli - Enterococci - Proteus - Klebsiella - Pseudomonas

Diabetic Foot Infections- Common Pathogens

Aerobic Pathogens - Gram-positive: S aureus (including MRSA), GAS, Viridians group Strep, S epidermidis - Gram-negative: E coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa. Anaerobic Pathogens - Gram-positive: Peptostreptococcus, Clostridium perfringens - Gram-negative: Bacteroides fragilis and others

Acute Otitis Media- Antibiotic Alternative Therapies and Dosing

Alternative Treatments (if Penicillin Allergy) - Cefdinir 14 mg/kg/day in 1 to 2 doses - Cefuroxime 30 mg/kg/day in 2 divided doses - Cefpodoxime 10 mg/kg/day in 2 divided doses - Ceftriaxone 50 mg/kg IM/IV for 1 to 3 days

Aminoglycosides- Overview, MOA, Summary of Coverage

Aminoglycosides bind to the ribosome, which interferes with bacterial protein synthesis and results in a defective bacterial cell membrane. They primarily cover gram-negative bacteria (including *pseudomonas*). Gentamicin and Streptomycin are used for *synergy* in combination with a beta-lactam or vancomycin when treating gram-positive infections (e.g. enterococcal endocarditis). Streptomycin and Amikacin are used as second-line treatment for Mycobacterial infections. Plazomicin, a newer drug in the class, is ONLY indicated for complicated UTI and Pyelonephritis when there are NO alternative options. Amikacin has the broadest spectrum of activity

Aminoglycosides- Dosing Strategies

Aminoglycosides have two different dosing strategies when used, Traditional Dosing and Extended-Interval Dosing. Both strategies use body weight to determine the amount that is given, and is based on either underweight, normal weight/overweight, or obesity. Traditional Dosing uses lower doses more frequently (e.g. q8hrs if renal function is normal). Extended-Interval Dosing uses higher doses to attain higher peak concentrations and is dosed less frequently (e.g. once daily if renal function is normal). Extended-Interval Dosing has less accumulation of the drug, which has been shown to decrease nephrotoxicity and decrease cost. However, this strategy has not been shown to be clinically superior to traditional dosing, only noninferior.

Aminopenicillins + Beta-lactamase Inhibitor Coverage and Drugs

Aminopenicillins combined with beta-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) have added coverage against: - MSSA - more resistant strains of gram-negative bacteria (the HNPEK group) - gram-negative anaerobes (B fragilis) - Amoxicillin/Clavulanate (Augmentin) - Ampicillin/Sulbactam (Unasyn)

Antibiogram

An antibiogram combines culture data from patients at a single institution into one chart (such as all gram-positive organisms cultured at that hospital). It provides susceptibility patterns at the hospital over a specific time period (typically 1 year). Bacteria are listed vertically on this antibiogram, and drugs are listed horizontally. The numbers inside the table are the % susceptibility of each organism to the listed drug. Antibiograms aid in selecting empiric treatment and are used to monitor resistance trends over time.

Synergy in Antibiotics

An infection could require more than one antibiotic for successful treatment. The effect of two antibiotics can be additive (equal to the sum of the individual drugs) or synergistic (equal to an effect greater than the sum of the individual drugs). In certain infections, synergy is useful. For example, aminoglycosides and beta-lactams can be used synergistically to treat invasive gram-positive infections (e.g. infective endocarditis). The beta-lactams allow the aminoglycoside easier access to its intracellular target, the ribosome, where it causes lethal damage to the bacteria. Without beta-lactams, aminoglycosides need really high doses to penetrate the cell wall. This synergy permits a lower dose of the aminoglycoside and clears the bloodstream infection more quickly.

Infectious Diseases

An infectious disease is caused by one or more pathogens (viruses, bacteria, fungi, protozoa, parasites, and/or infectious proteins [prions]). IDs are transmitted through various mechanisms, including physical contact with an infected individual or their body fluids, consuming contaminated food and water, or by touching contaminated objects. Some infections are transmitted by airborne inhalation and others may spread via a vector (carrier). Transmissible diseases that are spread from person to person are referred to as *communicable* or *contagious*.

Cephalosporins

Another type of Beta-lactam, this class has different generations and pathogen coverage varies based on the generation. As a class, cephalosporins are *not active against Enterococcus spp.* or *atypical organisms*. - First Generation - Second Generation - Third Generation - Fourth Generation - Fifth Generation - Siderophore Cephalosporins

Key Features of Quinolones

Antibiotic Coverage - The Respiratory Quinolones are Levofloxacin, Moxifloxacin, and Gemifloxacin, therefore they are useful for pneumonia (reliable S pneumoniae activity) - If Pseudomonas coverage is needed, Levofloxacin and Ciprofloxacin can be used (including pneumonias). - Ciprofloxacin and Levofloxacin are also useful in UTIs, Intra-Abdominal infections, and Traveler's Diarrhea (without Dysentery). Moxifloxacin - The ONLY quinolone that is not renally adjusted, however, it cannot be used in UTIs! IV to PO - Levofloxacin and Moxifloxacin are 1 to 1 IV to PO! Profile Review - Make sure to review the patient profile extensively and look for any CVD, hypoK, hypoMg, and if the patient uses any other QT-prolonging medications (such as Azoles, Antipsychotics, Methadone, or Macrolides) - Avoid in patients with a seizure history or if using seizure medications (or other medications that can decrease the seizure threshold) - Avoid use in children (EXCEPTION: Anthrax exposure) - Watch for tendon rupture, neuropathy, CNS or psychiatric side effects Counseling - Avoid sun exposure - Separate from cations - Monitor blood glucose (in Diabetes)

Antimicrobial Stewardship Programs

Antibiotic Stewardship Programs, or ASPs, are collaborative teams of infectious disease physicians, pharmacists, personnel from the microbiology lab, infection prevention and control, and information technology departments built to improve patient safety and outcomes, curb antibiotic resistance, reduce adverse effects, and promote cost-effectiveness. ASPs use guidelines, along with the local Antibiogram data, to establish antibiotic guidance for their facility. Most ASPs conduct audits of prescribing habits and provide education to change suboptimal prescribing habits and improve patient care. ASPs have been responsible for many new protocols in institutions, and create guidance for institutions to follow when dealing with antibiotics.

Antibiotic Selection- Antibiotic Characteristics

Antibiotic characteristics include the spectrum of activity and the ability for the antibiotic to penetrate to the site of the infection. Lipophilic antimicrobials have better tissue penetration. Hepatically cleared antibiotics may not have adequate concentration in the urine.

Antibiotic Resistance

Antibiotic resistance is the ability of an organism to multiply in the presence of a drug that normally limits its growth or kills it. These infections are difficult to treat and often require more drugs that are costly and/or toxic. Common mechanisms of resistance includes: - Intrinsic Resistance - Selection Pressure - Enzyme Inactivation

Antibiotic Selection

Antibiotics are selected based on the: - Infection Characteristics - Antibiotic Characteristics - Patient Characteristics

Severe Purulent Infections- Treatment

Antibiotics that cover MRSA, including CA-MRSA, are chosen, and the duration of therapy is 7-14 days. If the patient has had an animal or human bite, antibiotics are broadened to cover aerobic gram-negatives (including Pasteurella spp. for animal bites), gram-positives, and anaerobes (e.g. ampicillin/sulbactam, amoxicillin/clavulanate). Typical antibiotic choice includes: - *Vancomycin* (goal trough 10-15 mg/L) - *Daptomycin* - *Linezolid* - Telavancin - Ceftaroline - Tedizolid - Dalbavancin - Oritavancin Once clinically stable, transition to PO antibiotics

Atypical Bacteria

Atypicals are special when it comes to gram stains because they do not stain well. Common atypical infections include: - Chlamydia spp. - Legionella spp. - Mycoplasma pneumoniae - Mycobacterium tuberculosis

Isoniazid- Warnings and Contraindications

BOXED WARNING - Severe and fatal hepatitis Contraindications - Active liver disease - Previous severe adverse reaction to INH Warnings - Peripheral neuropathy, which occurs more often in patients predisposed to neuropathy (diabetes, HIV, renal failure, alcoholism, elderly, or in malnutrition). Pyridoxine supplementation is recommended for these patients and patients who are pregnant or breastfeeding.

Bacterial Vaginosis

Bacterial Vaginosis is an STI that is only seen in females (for obvious reasons). It is caused by many different organisms. Treatment is typically with Metronidazole PO, 0.75% Gel, or with Clindamycin 2% cream. Alternatives include Clindamycin PO or the ovules, Tinidazole, or Secnidazole. Regardless of treatment, patients with bacterial vaginosis *should not douche*.

Bacteriuria and Pregnancy

Bacteriuria, 10^5+ bacteria/mL on a urinalysis, in pregnant women *must be treated even if asymptomatic*. If not treated, bacteriuria can lead to pyelonephritis, premature birth, and neonatal meningitis. When treating bacteriuria, Beta-lactams are preferred (*Amoxicillin +/- Clavulanate or a Cephalosporin*). Nitrofurantoin or SMX/TMP may be used in cases of beta-lactam allergy, however, the American College of Obstetricians and Gynecologists (ACOG) states that these two should be avoided during the first trimester, and that there are safety issues later in pregnancy. Fosfomycin can be considered in pregnant patients who have drug allergies as well, but there is inferior efficacy as it is very narrow spectrum.

Beta-Lactam Antibiotics

Beta-Lactams, which include the Penicillins, Cephalosporins, and Carbapenems, are a class of antibiotics that have a chemical structure characterized by a beta-lactam ring. Beta-lactams work by inhibiting bacterial cell wall synthesis via binding to the penicillin-binding proteins (PBPs). Inhibition of these proteins prevents the final step of peptidoglycan synthesis in bacterial cells walls, causing cell death.

Key Counseling Points- Beta-Lactams, Macrolides

Beta-lactams - Cause cause seizures (with accumulation) Macrolides 1. Can cause - GI upset - QT prolongation 2. Azithromycin-specific - Z-pak: Take 2 tablets on day 1, followed by one tablet daily on days 2 to 5.

Tigecycline- Warnings, Side Effects

Black Box Warning - Increased risk of death when used. Use only when alternative treatments are not suitable. Other Warnings - Hepatotoxicity, pancreatitis, photosensitivity - Teeth discoloration in children <8 years of age, avoid use if at all possible (Tigecycline is a derivative of minocycline, which also has the same warning) - LOW CURE RATES in ventilator-associated pneumonia - Tigecycline can increase the INR in patients taking Warfarin Side Effects - N/V/D - Headache - Dizziness - Increased LFTs - Severe skin reactions (SJS/TEN)

Chloramphenicol- Warnings, Monitoring

Black Box Warning - Serious and fatal blood dyscrasias such as Aplastic Anemia and Pancytopenia have been reported, and these may be irreversible. Warnings - Gray Syndrome: A type of syndrome most commonly seen in newborn infants due to high serum concentrations of Chloramphenicol. It causes circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma, and death of the infant. Monitoring - CBC at baseline, then every 2 days during therapy - LFTs, renal function, and serum concentrations

Polymyxin B- Warnings, Monitoring

Black Box Warnings - DOSE-DEPENDENT NEPHROTOXICITY - Neurotoxicity (dizziness, tingling, numbness, paresthesia, vertigo) - Avoid concurrent or sequential use of other neurotoxic or nephrotoxic medications - Neurotoxicity can result in respiratory paralysis from neuromuscular blockade - ONLY ADMINISTER TO HOSPITALIZED PATIENTS Monitoring - Renal function

Differentiating Lyme Disease from Ringworm

Both Lyme Disease and Ringworm can present with a type of circular rash. The key difference between the two is the Lyme Disease rash will be a *bull's eye rash*, that is round and red. Lyme Disease will also present with achy joints and fever. Lyme Disease is diagnosed with an enzyme immunoassay (EIA) that identifies antibodies against Borrelia burgdorferi and/or mayonii. Ringworm will have a 1+ reddish raised ring rash, which can be itchy. It is caused by Tinea corporis and is treated with Clotrimazole or another topical antifungal.

Clindamycin- Warnings, Side Effects

Boxed Warning - Colitis due to C Difficile (BE SURE TO COUNSEL, HIGHEST RISK ANTIBIOTIC) Warning - Severe or fatal skin reactions (SJS/TEN/DRESS) Side Effects - N/V/D - Rash, Urticaria - Increase in LFTs (rare)

Penicillins- Boxed Warnings, Contraindications

Boxed Warning - Penicillin G Benzathine: NOT FOR IV USE. Can cause cardio-respiratory arrest and death Contraindications - Augmentin and Unasyn: History of cholestatic jaundice or hepatic dysfunction associated with previous use - Severe renal impairment (CrCl <30 mL/min): DO NOT USE EXTENDED-RELEASE oral forms of Amoxicillin and Augmentin OR 875 mg IR strength of Augmentin

Metronidazoles- Warnings, Contraindications

Boxed Warning - Possibly carcinogenic based on animal data with structurally similar drugs Contraindications - *Pregnancy (First trimester)* - Use of ALCOHOL or propylene glycol-containing products during treatment or within 3 days of treatment discontinuation *disulfiram reaction.* Warnings - CNS Effects: Seizures, peripheral neuropathy - Metronidazole-specific: Aseptic meningitis, encephalopathy, optic neuropathy

Bronchitis- Overview

Bronchitis is an inflammation of the mucous membranes of the bronchi. It is classified as either acute or chronic. Acute Bronchitis is typically a self-limited infection and can include a *productive cough* lasting more than 5 days (and up to 3 weeks), shortness of breath, nasal congestion, fatigue, and headache. Systemic symptoms, such as fever, can occur but are rare. Acute Bronchitis is primarily caused by respiratory viruses, including Respiratory Syncytial Virus (RSV), Adenovirus, Rhinovirus, Coronavirus, Influenza virus, and Parainfluenza virus. Bacterial causes are possible as well, and common infections include S pneumoniae, Mycoplasma pneumoniae, H influenzae, Bordetella pertussis (whooping cough), and Chlamydophilia pneumoniae. Diagnosis is usually made by ruling out other causes of acute cough, such as common cold, acute asthma, or pneumonia. Chest x-ray findings are typically *normal* and cultures are not routinely performed. Treatment is generally supportive (e.g. fluids to prevent dehydration, cough suppressants, expectorants, decongestants). Antibiotics are *not recommended* unless pneumonia is present. The exception to this is if Bordetella pertussis is present, which is treated with a Macrolide (Azithromycin, Clarithromycin) or SMX/TMP.

Community-Acquired Pneumonia

CAP is a lung infection contracted outside of healthcare facilities and can be bacterial, viral, or fungal (although fungal is rare). When symptoms are mild (e.g. the patient is not hospitalized and is able to complete daily activities), it can be termed *"walking pneumonia"*. Most bacterial causes of CAP are from *S pneumoniae, H influenzae, and M. pneumoniae*. It can possibly be caused by C pneumoniae.

Drugs of Choice- CRE

Carbapenem-Resistant Gram-Negative Rods - Ceftazidime/Avibactam - Colistimethate, Polymyxin B

Carbapenems

Carbapenems are very broad-spectrum antibiotics that are generally reserved for MDR gram-negative infections. They are active against most gram-positive, gram-negative (including ESBL-producing bacteria) and anaerobic pathogens. They are active against Enterococcus, but only Faecalis, not Faecium. However, carbapenems provide NO coverage of atypical pathogens, MRSA, VRE, C difficile, and Stenotrophomonas. Ertapenem is different from the other carbapenems in that it is NO ACTIVITY against Pseudomonas, Acinetobacter, or Enterococcus

Outpatient CAP Antibiotic Treatment Options

Category 1 (No Comorbidities) - Amoxicillin (high-dose), 1 gram TID OR - Doxycycline OR - Macrolide (Azithromycin or Clarithromycin) if local pneumococcal resistance is <25% Category 2 (Comorbidities present): Chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; or asplenia - Beta lactam PLUS a macrolide OR doxycycline (examples include Augmentin or a Cephalosporin (such as Cefpodoxime, Cefdinir, Cefuroxime). - Respiratory quinolone MONOTHERAPY (Moxifloxacin, Gemifloxacin, or Levofloxacin).

Cellulitis- Presentation, Bacteria

Cellulitis is a non-purulent infection that is typically only mild in presentation. It presents with localized pain, swelling, redness, and warmth, all often on the legs. Common bacteria includes Streptococci (including S pyogenes [Group A strep, GAS]), and S aureus.

Special Requirements: Diluent Compatibility Requirements

Certain IV antibiotics are only compatible with Dextrose, Saline or NS/LR. It is important to know these to prevent medication errors! Compatible with DEXTROSE ONLY: - Dalbavancin, Oritavancin - Pentamidine - Quinupristin/Dalfopristin - SMX/TMP - Amphotericin B (Conventional, Abelcet, Ambisome) Compatible with SALINE ONLY - Ampicillin - Ampicillin/Sulbactam - Ertapenem - Daptomycin (Cubicin RF) Compatible with NS/LR ONLY - Caspofungin - Daptomycin (Cubicin)

Chlamydia- Overview, Treatment

Chlamydia, or Chlamydia trachomatis, is an intracellular obligate gram-negative organism. It causes essentially the same symptoms as Gonorrhea (genital discharge or no symptoms at all) and is tested for in the exact same way (via the urethral, vaginal, cervical, rectal, or pharyngeal route). Treatment of Chlamydia is either with Azithromycin 1 gram PO once or *Doxycycline 100 mg PO BID for 7 days*. Azithromycin is preferred in pregnant women. Because of increased resistance of Gonorrhea to Azithromycin, Azithromycin is no longer preferred (Chlamydia and Gonorrhea like to hang out together). Alternatives include: - Erythromycin base 500 mg PO QID for 7 days - Levofloxacin 500 mg PO daily for 7 days - Ofloxacin 300 mg PO BID for 7 days - Amoxicillin (only in pregnant patients) Remember, Chlamydia and Gonorrhea often go together, so typically patients are also given Ceftriaxone 500 mg IM once (if <150 kg) or 1 gram IM once (if 150 kg or more) to cover Gonorrhea.

Chloramphenicol- Overview, Dosing and Administration

Chloramphenicol reversibly inhibits the 50S bacterial ribosome, inhibiting protein synthesis. It is broad-spectrum and covers gram-positives, gram-negatives, anaerobes, and atypical organisms. However, it is rarely used due to adverse effects. IV: 50-100 mg/kg/day in divided doses every 6 hours (MAX of 4 grams per day). No adjustment is needed in renal impairment, but use with caution.

Cholangitis

Cholangitis is an infection of the common bile duct and is generally managed with bile decompression and antimicrobial therapy. Likely pathogens and antimicrobial therapy selection are similar to secondary peritonitis. This means the most likely pathogens are Streptococci, enteric gram-negatives, and anaerobes (Bacteroides fragilis). In more severe cases, coverage of Pseudomonas and CAPES organisms may be necessary.

Cholecystitis

Cholecystitis is an acute inflammation of the gallbladder due to an obstructive stone. It is usually managed surgically with a cholecystectomy. Infection may not be the precipitating factor, but is present in 50% of cases. If infection is present, likely pathogens and antimicrobial selection are similar to Primary Peritonitis. This means the most likely pathogens are Streptococci, enteric gram-negative organisms (Proteus, E coli, and Klebsiella, or PEK) and rarely, anaerobes. Drug of choice is Ceftriaxone with alternative treatments being Ampicillin, Gentamicin, or a Quinolone.

Quinolones- Clinical Pearls

Cipro Oral Suspension - Shake vigorously for 15 seconds before each use. - DO NOT put through a nasogastric or any other feeding tube (oil-based suspension that adheres to tubing) Cipro - Immediate-release tablets can be crushed, mixed with water, and given through a feeding tube HOWEVER, hold tube feedings at least 1 hour before and 2 hours after the dose. Moxifloxacin - DOES NOT reach adequate concentrations in the urine and SHOULD NOT be used for UTIs.

Clindamycin- Overview

Clindamycin, Cleocin, is a Lincosamide Antibiotic, which reversibly binds to the 50S ribosome of the bacterial ribosome inhibiting protein synthesis. It covers most anaerobes and gram-positive bacteria (including some CA-MRSA). It does NOT cover Enterococci or Gram-negative pathogens. Clindamycin is available as an injection, capsule, suspension, and topically. The topical version (Cleocin-T, Clindagel) comes in a foam, gel, lotion, kit, solution, and swab. There are also special vaginal formulations that come in a cream, and suppository. Clindamycin is commonly used for purulent and non-purulent skin infections, and as a beta-lactam alternative for dental abscesses.

Collateral Damage

Collateral Damage refers to the unintended consequences of antibiotic use. Antibiotics kill normal, healthy GI flora along with the pathogens they are targeting. This results in an overgrowth of organisms that are resistant to the drug and can lead to superinfections, such as Clostridium (Clostridioides) Difficile Infections (CDI). CDI has become much more common in recent years. ALL antibiotics have a warning for the risk of CDI, but some classes are associated with a higher risk than others. Clindamycin has a black box warning for CDI, and should be counseled on.

Diabetic Foot Infections- Combination Therapy

Combination therapy is done when MRSA and Pseudomonas coverage is needed. Start Vancomycin plus one of the following: - Ceftazidime, Cefepime, Piperacillin/tazobactam, Aztreonam, or a Carbapenem (except Ertapenem), as these all have Pseudomonas coverage Consider adding anaerobic coverage (Metronidazole) if Ceftazidime, Cefepime, or Aztreonam are selected. Vancomycin can be substituted for Daptomycin, or Linezolid.

Tetracyclines- Key Features

Common Uses - Doxycycline and Minocycline: CA-MRSA skin infections, acne - Doxycycline: First-line for Lyme Disease, Rocky Mountain Spotted Fever (tick-borne illnesses), CAP, COPD exacerbations, sinusitis (if antibiotics are needed), and VRE UTI. Doxycycline is also monotherapy for Chlamydia and combination therapy for Gonorrhea. Other Considerations - DO NOT USE IN PREGNANCY, BREASTFEEDING, OR CHILDREN UNDER 8 YEARS OF AGE

HAP/VAP Treatment- Risk for MRSA or MDR Pathogens

Common case clues that identify increased risk for MRSA or MDR Pathogens include: - Positive MRSA nasal swab (indicating MRSA colonization) - High prevalence of resistant pathogen noted in hospital unit - IV antibiotic use within the past 90 days

Community-Acquired Pneumonia- Symptoms, Diagnosis

Common pneumonia symptoms include a fever, *cough with purulent sputum*, pleuritic chest pain, *rales* (crackling noises in the lungs), decreased breath sounds, and *tachypnea* (increased respiratory rate). A chest x-ray is the GOLD STANDARD test for diagnosis and will have *"infiltrates," "opacities." or "consolidations"* to indicate pneumonia.

Lower Respiratory Tract Common Bacterial Pathogens (Community and Hospital)

Community - Streptococcus pneumoniae - Haemophilus influenzae - Atypicals: Legionella, Mycoplasma - Enteric Gram-negative rods (in alcoholics, immunocompromised) Hospital - Staphylococcus aureus, including MRSA - Pseudomonas aeruginosa - Enteric Gram-negative rods - Streptococcus pneumoniae

Complicated UTI- Overview and Bacteria

Complicated UTIs include men or those who have catheters or some other obstruction in the urinary tract. It can be treated similarly to acute pyelonephritis as many of the same bacteria responsible for pyelonephritis are seen in Complicated infections, however, there are some unique pathogens as well. Common bacteria include: - E Coli - Klebsiella - Enterobacter - Serratia - Pseudomonas - Enterococci - Staphylococci

Pyrazinamide- Contraindications, ADEs

Contraindications - *Acute gout* - Severe hepatic damage Side Effects - Increased LFTs - Hyperuricemia/gout - GI upset - Malaise - Arthralgias - Myalgias - Rash

Carbapenems- Contraindications and Warnings

Contraindications - Anaphylactic reactions in beta-lactam antibiotics Warnings - DO NOT USE IN PATIENTS WITH PENICILLIN ALLERGIES. Cross reactivity has been reported to be as high as 50%, but more recent studies show rates of <10% - CNS Adverse Effects, including states of confusion and SEIZURES - Doripenem: Do not use for the treatment of pneumonia, including healthcare-acquired pneumonia and ventilator-acquired pneumonia

Telavancin- Contraindications, Warnings

Contraindications - Concurrent use of IV Unfractionated Heparin Warnings - Can *falsely* elevate coagulation tests (aPTT, PT, INR), but this does not confer an increased bleeding risk - Red Man Syndrome with rapid IV administration. Can be avoided if given over 60+ minutes - QT Prolongation

Linezolid- Contraindications, Warnings

Contraindications - DO NOT USE WITH OR WITHIN 2 WEEKS OF MAOI INHIBITORS Warnings - Duration-related myelosuppression including thrombocytopenia, anemia, and leukopenia - Peripheral and optic neuropathy when used for >28 days - Serotonin Syndrome - Hypoglycemia (caution with insulin use or with other hypoglycemic medications) - Seizures - Lactic Acidosis - Elevated BP: Use caution and monitor BP in patients with uncontrolled hypertension and untreated hyperthyroidism

Rifampin- Contraindications, ADEs

Contraindications - DO NOT USE WITH PROTEASE INHIBITORS (PIs) Side Effects - Increase in LFTs - Hemolytic anemia (detected with a positive Coombs test) - Flu-like syndrome - GI upset - Rash/pruritus - Orange/red discoloration of body secretions (sputum, urine, sweat, tears, teeth), which can stain contact lenses and clothing

Other Lipoglycopeptides- Contraindications, Warnings

Contraindications - ORITAVANCIN ONLY: Use of IV UFH for 120 hours (5 days) after Oritavancin administration due to interference (false elevations) with aPTT laboratory results Warnings - BOTH: Can *falsely* elevate PT/INR for up to 12 hours and aPTT for up to 120 hours after a dose - ORITAVANCIN: Use a different antibiotic if osteomyelitis is confirmed or suspected - DALBAVANCIN: Red Man Syndrome with rapid IV administration, infuse over at least 30 minutes. - DALBAVANCIN: Increase in ALT >3x the upper limit of normal is possible

Ethambutol- Contraindications, ADEs

Contraindications - Optic neuritis (risk vs benefit decision): Do not use in young children, unconscious patients, or any patient who CANNOT discern and report visual changes Side Effects - Increased LFTs - Optic neuritis (dose-related) - Decreased visual acuity - Partial loss of vision/blind spot and/or color blindness (usually reversible) - Rash - Headache - *Confusion, hallucinations* - Nausea/vomiting

Nitrofurantoin- Contraindications, Warnings

Contraindications - Renal impairment (CrCl <60): Inadequate urine concentrations and risk for accumulation of neurotoxins - Previous history of cholestatic jaundice/hepatic dysfunction - Pregnancy (at term) Warnings - Optic neuritis - Hepatotoxicity - Peripheral neuropathy - Pulmonary toxicity - Hemolytic anemia (use with caution in those with G6PD deficiency)

Quinolones- Contraindications and Warnings

Contraindications: - Ciprofloxacin ONLY: Concurrent administration of Tizanidine. Warnings: - QT Prolongation (highest risk with moxifloxacin): Avoid in patients with known QT prolongation, or those with additive risks (hypokalemia, use of other drugs that prolong the QT, including class Ia and class III antiarrhythmics). - Hypo/hyperglycemia: Hypoglycemia can lead to coma. - Psychiatric Disturbances: Agitation, Disorientation, Lack of attention, Nervousness, Memory impairment, and Delirium. - Avoid systemic use in children or in pregnancy/breastfeeding: Quinolones have a risk of musculoskeletal toxicity (EXCEPTION: in anthrax exposure, the benefits of Quinolones outweigh the risks). - Other Warnings: Photosensitivity, Phototoxicity, Aortic Aneurysm, Aortic Dissection, Hepatotoxicity, Crystalluria (stay well-hydrated while taking)

First Generation Cephalosporins- Coverage and Drugs

Coverage - Excellent coverage of gram-positive cocci (e.g. streptococci and staphylococci) and preferred when a cephalosporin is used for *MSSA*. - They have some activity against the gram-negative rod group PEK (Proteus, E. Coli, Klebsiella), but in general, gram-negative activity is decreased compared to the 2nd-4th generations. Drugs - Cefazolin - Cephalexin - Cefadroxil

Fourth Generation Cephalosporins- Coverage and Drugs

Coverage - Only includes Cefepime, which has broad-spectrum gram-negative activity (HNPEK, CAPES, Pseudomonas), and gram-positive activity similar to Ceftriaxone (more resistant Streptococci [Pneumoniae and viridians group], Staphylococci [MSSA], and gram-positive anaerobes [mouth flora]). Drugs - Cefepime (Maxipime)

Fifth Generation Cephalosporins- Coverage and Drugs

Coverage - Only includes Ceftaroline, which has gram-negative activity similar to ceftriaxone (more resistant strains of HNPEK), but has broad-spectrum gram-positive activity, including *MRSA*. It is the only beta-lactam that covers MRSA. Drugs - Ceftaroline Fosamil (Teflaro)

Third Generation Cephalosporins- Coverage and Drugs

Coverage - There are two groups of third generation cephalosporins. Group 1 includes Ceftriaxone and Cefotaxime and oral drugs, which cover more resistant Streptococci (Pneumoniae and viridians group), Staphylcocci (MSSA), Gram-positive anaerobes (mouth flora), and more resistant HNPEK. - Group 2 includes ceftazidime, which lacks gram-positive activity, but covers Pseudomonas, and the newer beta-lactamase inhibitor combinations, ceftazidime/avibactam and ceftolozane/tazobactam, which have added activity against MDR Pseudomonas and other MDR gram-negative rods. However, the two beta-lactamase inhibitor combinations must be combined with Metronidazole to have adequate anaerobic coverage. Ceftazidime by itself does not cover anaerobes. Drugs 1. Group #1 - Cefdinir (Omnicef) - Ceftriaxone (Rocephin) - Cefotaxime - Cefditoren (Spectracef) - Cefixime (Suprax) - Cefopodoxime - Ceftibuten 2. Group #2 - Ceftazidime (Fortaz, Tazicef) - Ceftazidime/Avibactam (Avycaz) - Ceftolozane/Tazobactam (Zerbaxa)

Second Generation Cephalosporins- Coverage and Drugs

Coverage - There are two types of second generation. Drugs like cefuroxime cover Staphylococci, more resistant strains of S. pneumoniae, plus Haemophilis, Neisseria, Proteus, E Coli, and Klebsiella (HNPEK). - Cefotetan, and Cefoxitin (group 2) have added coverage of gram-negative anaerobes (B fragilis). Drugs 1. Group 1: - Cefuroxime (Ceftin) - Cefaclor - Cefprozil 2. Group 2: - Cefotetan (Cefotan) - Cefoxitin

Siderophore Cephalosporins- Coverage and Drugs

Coverage - This special beta-lactam, Cefiderocol, uses the iron transport system to enter the gram-negative cell wall. It is approved for complicated UTI/pyelonephritis and active against E Coli, Enterobacter, Klebsiella, Proteus, and Pseudomonas. Drugs - Cefiderocol (Fetroja)

Gram Staining

Cultures of the infection site are taken (e.g. lung secretions, urine, blood, or tissue from a wound or abscess) and sent to the microbiology lab. The lab performs a gram stain, which is a simple test that helps to identify the causative organism. These stains help organize the pathogen by shape or morphology, which can direct the use of empiric antibiotics or help rule out possible causative agents. Bacteria can be gram-positive, gram-negative, or Atypical, based on how they stain on this test. This test provides quick, preliminary results (e.g. gram-negative rods) but does not identify the exact organism. The gram stain results provide a clue about what organism may be causing the infection and an opportunity to adjust the empiric antibiotic regimen.

Ceftriaxone in Neonates

DO NOT USE CEFTRIAXONE IN NEONATES! Ceftriaxone can cause biliary sludging, which are solids that precipitate from bile, and Kernicterus (brain damage from high bilirubin) in neonates.

Infective Endocarditis- Dental Prophylaxis High Risk Individuals

Dental work needed, such as a root canal + select cardiac conditions, such as: - Artificial (prosthetic) heart valve or heart valve repaired with artificial material - History of endocarditis - Heart transplant with abnormal heart valve function - Certain congenital heart defects, including heart/heart valve disease

Meningitis- Diagnosis

Diagnosis is made with a Lumbar Puncture (LP), which takes a sample of the Cerebrospinal Fluid (CSF) and analyzes it to help guide drug selection before the culture and susceptibility results are available. Some patients need a Computed Tomography (CT) scan prior to the LP to rule out other issues, such as stroke. It is preferable to get the LP prior to starting antibiotics, BUT, antibiotics should be given quickly, even when the LP is delayed.

Disulfiram-like Reaction

Disulfiram is a medication that is used in alcohol dependence, and works by inhibiting aldehyde dehydrogenase. This causes the alcohol to not be metabolized to its end product, and instead build up as the poison Acetaldehyde. This causes abdominal cramping, nausea, vomiting, headaches, and flushing, like an extremely bad hangover.

Sulfonamide Antibiotics- Dosing

Dose of SMX/TMP (including weight-based dosing) is *always based on the TMP component*. 1. Severe infections - PO/IV: 10-20 mg TMP/kg/day divided q6-8hrs (e.g. 2 DS tablets BID-TID) 2. Uncomplicated UTI - *1 DS tablet PO BID x 3 days* 3. Pneumocystis Pneumonia (PCP) Prophylaxis: - 1 DS or SS tablet DAILY 4. PCP Treatment: - IV/PO: 15-20 mg TMP/kg/day divided q6hrs - CrCl 15-30 ml/min: Dose adjustment required - CrCl <15: NOT RECOMMENDED

Lefamulin- Dosing, Contraindications, Warnings, Side Effects

Dosing - PO: 600 mg every 12 hours - IV: 150 mg every 12 hours Contraindications - Use with CYP3A4 substrates that prolong the QT interval Warnings - Avoid in pregnancy (teratogenic) - QT Prolongation - C Diff-associated diarrhea Side Effects - Diarrhea, nausea, injection site reactions

Vancomycin- Drug Names and Dosing

Drug Names - Vancocin, Firvanq Oral Solution - Available as a capsule, oral solution, and injection Systemic Infection Dosing (IV ONLY) - Typically 15-20 mg/kg every 8 to 12 hours - Dosing is based on TOTAL BODY WEIGHT - CrCl 20-49 mL/min: give every 24 hours - CrCl <20: Dose ONCE then dose based on levels - Peripheral IV infusions should NOT exceed 5 mg/mL C. Difficile Infection Dosing (PO ONLY) - Typically 125 to 500 mg QID for 10 days (upper end of dosing is used for severe, complicated disease) - NO DOSE ADJUSTMENT in renal impairment

Bacterial Vaginosis- Treatment Regimens

Drugs of Choice - Metronidazole 500mg PO BID for 7 days. - Metronidazole 0.75% gel, 1 applicatorful intravaginally once daily or BID for 5 days. - Clindamycin 2% cream, 1 applicatorful intravaginally at bedtime for 3 to 7 days. Alternatives - Clindamycin PO 300 mg BID for 7 days - Clindamycin ovules, 100 mg intravaginally at bedtime for 3 days - Tinidazole 2 grams PO daily for 2 days OR 1 gram PO daily for 5 days - Secnidazole 2 grams PO once The Clindamycin ovules use a base that can weaken latex or rubber products (i.e., condoms). Use an alternative form of contraception within 72 hours of Clindamycin ovules.

Cephalosporins- Drug Interactions

Drugs that decrease stomach acid can decrease the bioavailability of *some* cephalosporins. - Separate Cefuroxime, Cefpodoxime, Cefdinir, and Cefditoren by two hours from short-acting antacids. H2RAs and PPIs should be avoided.

Concentration-Dependent Killing

Drugs with concentration-dependent killing, such as Aminoglycosides, are typically dosed less frequently and in higher doses to maximize the concentration above the MIC. The goals are to have a very high peak concentration (to maximize killing) and a very low trough (to decrease toxicities) Common antibiotics that use CDK: - Aminoglycosides - Quinolones - Daptomycin The dosing strategy used in CDK antibiotics is to give a fairly high dose and have a long interval in between each dose.

Time-Dependent Killing

Drugs with time-dependent killing, such as beta-lactams, are typically dosed more frequently or administered for a longer total duration to maximize the time above the MIC. Examples to increase the duration includes extending the infusion time or administering the drug as a continuous infusion. Studies have shown that extended/continuous infusions of beta-lactams reduce hospital length of stay, mortality, and costs, particularly when treating pneumonia caused by MDR gram-negative pathogens like Pseudomonas. Common antibiotics that use TDK: - Beta-lactams (penicillins, cephalosporins, carbapenems) The common dosing strategies to maximize TDK is to use a shorter dosing interval, have an extended infusion, or place a continuous infusion.

Drugs of Choice- ESBL GNR

ESBL GNR, Extended Spectrum Beta-Lactamase Producing Gram-Negative Rods, includes E Coli, Klebsiella Pneumoniae, and Proteus Mirabilis - Carbapenems - Ceftolozane/Tazobactam - Ceftazidime/Avibactam - Cefepime (High dose) - Aminoglycosides - CYSTITIS ONLY: Fosfomycin

Extended-Spectrum Penicillins Coverage and Drugs

ESPs, combined with a beta-lactamase inhibitor have BROAD SPECTRUM activity. They cover the same organisms as the aminopenicillin/beta-lactamase inhibitor combinations, plus have expanded coverage of other gram-negative bacteria including the CAPES group and Pseudomonas Aeruginosa. - Streptococci - Enterococci - Gram-positive anaerobes (mouth flora) - More resistant HNPEK - Gram-negative anaerobes (B fragilis) - CAPES (Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia) - Pseudomonas aeruginosa - MSSA Drugs - Piperacillin/Tazobactam (Zosyn)

Ehrlichiosis- Organism and Treatment

Ehrlichiosis is caused by Ehrlichia chaffeensis, an obligate intracellular gram-negative bacteria. Treatment is with Doxycycline 100 mg PO/IV BID for 7 to 14 days.

Empiric Treatment

Empiric Treatment is the first round of antibiotics given before the pathogen is identified. This empiric regimen is usually broad-spectrum, meaning they cover several different types of bacteria, and is based on a best-guess of the likely organisms causing the infection. The supposed location of the infection, symptoms of the infection, local resistance patterns, and antibiotic guidelines are all typically considered when selecting empiric treatment. Local resistance patterns are identified based on an antibiogram or other methods. They take into account resistance at the hospital and resistance in the community.

Ethambutol- Name, Dosing, Administration

Ethambutol - Available by itself (Myambutol) Dosing - 15-20 mg/kg (max 1.6 grams) PO daily OR - 25-30 mg/kg (max 2.4 grams) 3x a week OR - 50 mg/kg (max 4 grams) 2x a week - CrCl <50: extend dosing interval

ASP Interventions and Guidance

Examples of ASP interventions include: - Pharmacokinetic monitoring of aminoglycosides and vancomycin to optimize doses and minimize toxicities - Rapid identification of pathogens and shortened time to starting effective treatment using specialized computer software that integrate rapid diagnostic test results with patient information - Preauthorization of select antimicrobials - Timely transitions from IV to PO antibiotics

Fidaxomicin

Fidaxomicin (Dificid) is a special antibiotic that is only used for C difficile infections. It inhibits C Diff RNA polymerase, resulting in inhibition of protein synthesis, causing cell death. Dificid is given as a tablet only, and is dosed at 200 mg twice a day for 10 days. There are no adjustments needed for renal impairment. Absorption of the compound is very minimal, making it very useful for C Diff, but not effective for systemic infections. Side effects include N/V, abdominal pain, GI bleeding, and anemia (due to bleeding).

Sinusitis- Treatment

First-Line: - *Amoxicillin/Clavulanate Second-Line (Failure of first-line treatment) - Oral 2nd/3rd generation cephalosporin + clindamycin, doxycycline, or a respiratory quinolone (levofloxacin, moxifloxacin, gemifloxacin). Treatment duration varies based on the antibiotic. Symptoms can be managed with OTC products such as decongestants, antihistamines, etc.

Folliculitis, Furuncles, Carbuncles- Presentation, Bacteria

Folliculitis - This is inflammation of a hair follicle that looks like a red pimple Furuncle (boil) - This is an infection in the hair follicle and the surrounding tissue Carbuncle - A group of infected Furuncles The common cause of these is typically S. aureus, including Community-Acquired MRSA (CA-MRSA).

Folliculitis, Furuncles, Carbuncles- Treatment

Folliculitis and Furuncles may require only warm compresses to decrease inflammation and help with drainage. Carbuncles require incision and drainage (I&D) to drain pus. If there are systemic signs and symptoms, use antibiotics that cover MSSA: *Cephalexin 500 mg* PO QID. If non-responsive to initial treatment, change to a drug with CA-MRSA coverage: - *SMX/TMP DS* 1 to 2 tablets PO BID - *Doxycycline 100 mg* PO BID Occasionally, Folliculitis is due to a fungal infection and can be treated with *Ketoconazole* cream.

Special Requirements: 1 to 1 IV to Oral Dosing

For these medications, the oral and IV dose are the same: - Levofloxacin, Moxifloxacin - Doxycycline, Minocycline - SMX/TMP - Linezolid, Tedizolid - Metronidazole - Fluconazole, Isavuconazonium, Posaconazole (tablets and IV only), Voriconazole

Fosfomycin

Fosfomycin (Monurol) is a urinary antibiotic that is used in females for uncomplicated UTI. It inhibits bacterial cell wall synthesis by inactivating the enzyme pyruval transferase, which is critical in the synthesis of cell walls. Fosfomycin is active against E Coli (including ESBL), and E Faecalis (including VRE). It is a single dose regimen of 3 grams (1 packet granules) mixed in 3 to 4 oz of cold water and taken by mouth. Side effects include headache, diarrhea, and nausea.

Genital Warts- Overview

Genital Warts is an STI that causes benign warts on the genitalia and they may or may not cause pain. It is caused by HPV, or Human Papillomavirus. If the patient has warts, they can be treated with *Imiquimod cream* (Aldara, or Zyclara). Certain strains of HPV have been found to cause cervical, vaginal, and penile cancer. The *Gardasil vaccine* protects against the strains that have been known to cause cancer and is recommended in patients at risk for HPV to reduce the risk of cervical and other types of cancer.

Aminoglycosides- Traditional Dosing

Gentamicin and Tobramycin: *1-2.5 mg/kg/dose* - Lower doses are used for gram-positive infections and higher doses are used for gram-negative infections Amikacin: 5-7.5 mg/kg/dose q8hrs Renal Dose Adjustments: - *CrCl 60+ mL/min: q8hrs* - CrCl 40-<60 mL/min: q12hrs - CrCl 20-<40 mL/min: q24hrs - CrCl <20 mL/min: Give 1 dose then dose again based on levels Plazomicin 15 mg/kg IV q24hrs (dose adjustments required if CrCl <60 mL/min).

Aminoglycosides- Extended Interval Dosing

Gentamicin and Tobramycin: *4-7 mg/kg/dose (commonly 7 mg/kg)* - Frequency of dosing is determined by a nomogram. - Avoid when clearance and/or the volume of distribution are altered (typically in pregnancy, ascites, burns, cystic fibrosis, or CrCl <30 mL/min [including ESRD on dialysis]).

Gonorrhea- Overview

Gonorrhea, a classic STI, is caused by Neisseria gonorrhoeae, a gram-negative diplococcus. It causes either genital discharge or no symptoms at all. Gonorrhea does not like to infect alone, and is often present with Chlamydia, which also causes the same symptoms. Treatment is typically aimed at just treating for both, as it is difficult to differentiate between the two. Monotherapy with an antibiotic used to not be recommended, but due to increased resistance of N. gonorrhoeae to Azithromycin, monotherapy with high-dose Ceftriaxone is not the preferred regimen. If necessary, patients can be tested for Gonorrhea via the urethral, vaginal, cervical, rectal, or pharyngeal route.

Gram-Negative Stain Results

Gram-Negative organisms have a thin cell wall and take up the safranin counterstain, resulting in a pink or reddish color. When stained we can see the morphology, which can be cocci, rods, coccobacilli, or anaerobes. Cocci gram-negatives are balls, and typically means the infection is Neisseria spp. Rod gram-negatives are split into three different types, those that colonize the gut, those that do not colonize the gut, or those that appear curved or spiral shaped on the stain. - If it colonizes the gut, these are "enteric" pathogens, or part of the enteric GNR group. These pathogens are typically Proteus mirabillis, Escherichia coli, Klebsiella spp, Serratia spp, Enterobacter cloacae, or Citrobacter spp. - If it does not colonize the gut, then it is a "non-enteric" GNR. These pathogens are typically Pseudomonas aeruginosa, Haemophilus influenzae, or Providencia spp. - The special curved or spiral shaped GNRs appear tell us the infection is typically H pylori, Campylobacter spp, Treponema spp, Borrelia spp, or Leptospira spp. Coccobacilli are a special type of gram-negatives that appear as oblong balls (oval shaped) or rods that are in lines. Common coccobacilli infections are Acinetobacter baumanii, Bordetella pertussis, and Moraxella catarrhalis. Other gram negatives include the anaerobes, which are typically Bacteroides fragilis and Prevotella spp.

Gram Positive Stain Results

Gram-Positive organisms have a thick cell wall and stain dark purple or bluish from the crystal violet stain. When stained, we can see the morphology, whether they are cocci (balls), rods, or an anaerobe. Gram-positive cocci will typically appear in either clusters or pairs/chains. - A cluster typically means the organism is Staphylococcus spp, which includes MRSA or MSSA. - A pair/chain typically means the organism is Streptococci or Enterococci. Streptococci, usually streptococci pneumoniae, appears in pairs (termed diplococci). Other Streptococci, including Streptococci pyogenes, will be in chains. A rod morphology typically means the infection is Listeria monocytogenes An anaerobe infection typically means the infection is Peptostreptococcus, Actinomyces spp, or Clostridium (clostridioides) spp.

HAP and VAP

HAP and VAP are Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia. HAP is diagnosed when the onset is >48 hours after hospital admission while VAP is diagnosed when it occurs >48 hours after the start of mechanical ventilation. HAP is the leading infectious cause of death in ICU patients, whereas VAP can negatively impact patient outcomes (prolonged duration of ventilation and hospitalization). The rate of VAP can be reduced by proper handwashing, elevating the head of the bed by 30+ degrees, weaning off the ventilator ASAP, removing nasogastric tubes when possible and discontinuing stress ulcer prophylaxis.

Drugs of Choice- HNPEK

Haemophilus, Neisseria, Proteus, E. Coli, Klebsiella - Beta-Lactam/Beta-Lactamase Inhibitor - Amoxicillin (if beta-lactamase negative) - Cephalosporins (except *1st Generation*) - Carbapenems - SMX/TMP - Aminoglycosides - Quinolones

Secondary Peritonitis and Cholangitis- High-severity Infections Treatment Regimens

High-severity infections will typically be caused by PEK, CAPES, Pseudomonas, Anaerobes, Streptococci +/- Enterococci - Carbapenems (EXCEPT Ertapenem) - Piperacillin/Tazobactam - Cefepime or Ceftazidime PLUS Metronidazole - Ciprofloxacin or Levofloxacin PLUS Metronidazole - Cefazolin PLUS Metronidazole PLUS Aztreonam or an Aminoglycoside Remember, PEK is Proteus, E Coli, and Klebsiella. CAPES are nosocomial GNRs: Citrobacter, Acinetobacter, Providencia, Enterobacter, and Serratia.

Hydrophilic Antibiotic Properties

Hydrophilic antibiotics such as beta-lactams, aminoglycosides, vancomycin, daptomycin, and the polymyxins have the following characteristics: - Small volume of distribution causing poor tissue perfusion - Renal elimination, potentially causing nephrotoxicity or accumulation of the drug in renal dysfunction/impairment - Low intracellular concentrations, meaning they will not be active against atypical (intracellular) pathogens - Increased clearance and/or distribution in sepsis, due to the dynamics of sepsis. Consider loading doses and/or aggressive dosing if using these agents in the setting of sepsis - Poor/Moderate bioavailability. These agents are either not used PO, or the IV:PO ratio is NOT 1:1

Hydrophilic vs Lipophilic Antibiotics

Hydrophilicity or Lipophilicity of the antibiotic can be used to predict a number of the pharmacokinetic parameters of the drug, which determines its effectiveness in certain infections and how the body manages it. Hydrophilic Agents - Beta-Lactams - Aminoglycosides - Glycopeptides (Vancomycin) - Daptomycin - Polymyxins Lipophilic Agents - Quinolones - Macrolides - Rifampin - Linezolid - Tetracyclines

Infective Endocarditis- Treatment Overview

IE is generally fatal if left untreated. Empiric therapy often includes Vancomycin and Ceftriaxone. Definitive treatment, and the antibiotic duration, are dependent on the pathogen, the type of infected valve (native or prosthetic) and the susceptibility results. Gentamicin is added to the antimicrobial regimen for synergy when the infection is more difficult to eradicate, such as with prosthetic valve infections or when treating more resistant organisms. In some cases the risk of additive nephrotoxicity outweighs the benefit and it is left off the regimen (such as when Vancomycin is used for streptococcal endocarditis in patients with a beta-lactam allergy). When Gentamicin is used for synergy, traditional dosing is typically used to target peak levels of 3-4 mcg/mL and trough levels of <1 mcg/mL. Extended interval dosing of aminoglycosides is less common when treating IE. Some bacteria can form a biofilm, a slime layer, on the valve (especially on prosthetic valves). This makes it very difficult for some antibiotics to penetrate. Rifampin is used in cases of Staphylococcal prosthetic valve endocarditis, due to its ability to treat organisms in a biofilm.

Clostridium Difficile Infection- Subsequent Episodes

If after the first recurrence patients have another infection, treatment must be creative and/or combine multiple regimens. 1. Vancomycin tapered and pulsed regimen OR 2. Vancomycin 125 mg PO QID for 10 days then Rifaximin 400 mg TID for 20 days OR 3. Fidaxomicin 200 mg PO BID for 10 days OR 4. Fecal microbiota transplant

Acute Uncomplicated UTI- Prophylaxis

If patients have 3+ episodes of UTIs in 1 year, prophylaxis with antibiotics may be warranted. Recommended prophylactic regimens include: 1. SMX/TMP SS 1 tablet PO daily 2. Nitrofurantoin 50mg PO daily 3. SMX/TMP DS 1 tablet PO after sexual intercourse

Complicated UTI- Moderate Treatment

If the local Quinolone resistance is 10% or less, treatment is with either: - Ciprofloxacin 500 mg PO BID (or ER 1,000 mg PO QD) for 7 days OR - Levofloxacin 750 mg PO daily for 5 days If the local Quinolone resistance is >10%, treatment must be with another type of antibiotic. - Ceftriaxone 1 gram IM/IV once OR Aminoglycoside extended-interval dose IM/IV once, then continue with a Quinolone as above for 5 to 7 days - SMX/TMP for 14 days - Beta-lactam (Augmentin, Cefdinir, Cefaclor, or Cefpodoxime) for 10-14 days

Treatment and Antibiotic Criteria in ABECB

If the patient has ABECB, they are immediately started on *supportive treatment* (e.g. oxygen, short-acting inhaled bronchodilators, IV or PO steroids). They are started on antibiotics for 5 to 7 days IF: 1. All three of the following: increased dyspnea, increased sputum volume, and increased sputum purulence OR 2. Increased sputum purulence plus 1 additional symptom OR 3. Mechanically ventilated The preferred antibiotics are Amoxicillin/Clavulanate, Azithromycin, or Doxycycline

CAP Antibiotic Treatment with MRSA/Pseudomonas Risk Factors

If the patient has risk factors for MRSA and/or Pseudomonas, the antibiotic therapy changes. If MRSA risk factors, add coverage with Vancomycin or Linezolid. If Pseudomonas risk factors, add coverage with *Piperacillin/Tazobactam*, *Cefepime*, Ceftazidime, Imipenem/Cilastatin, *Meropenem*, or *Aztreonam*.

Acute Uncomplicated Pyelonephritis- Moderate Treatment

If the patient is only moderately ill, so they are able to treat the infection as an outpatient, treatment depends on the resistance patterns of the pathogen, particularly resistance against Quinolones. If the local Quinolone resistance is 10% or less, treatment is with either: - Ciprofloxacin 500 mg PO BID (or ER 1,000 mg PO QD) for 7 days OR - Levofloxacin 750 mg PO daily for 5 days If the local Quinolone resistance is >10%, treatment must be with another type of antibiotic. - Ceftriaxone 1 gram IM/IV once OR Aminoglycoside extended-interval dose IM/IV once, then continue with a Quinolone as above for 5 to 7 days - SMX/TMP for 14 days - Beta-lactam (Augmentin, Cefdinir, Cefaclor, or Cefpodoxime) for 10-14 days

Acute Uncomplicated UTI- Pregnancy Options

If the patient is pregnant and has all the other characteristics of an uncomplicated UTI (15-45 years old), they can be treated with: - *Cephalexin* - *Amoxicillin* - Fosfomycin (if beta-lactam allergy) Pregnant women with acute cystitis should be treated for 7 days. Those that are asymptomatic should be treated for 3-7 days.

Acute Uncomplicated Pyelonephritis- Severe Treatment

If the patient is severely ill, meaning they are in the hospital or requires inpatient treatment, they will get IV therapy then step down to oral treatment options based on culture and susceptibility. Total treatment duration is 14 days (including IV and PO therapy). Initial therapy is with Ciprofloxacin or Levofloxacin, Gentamicin (+/- Ampicillin, Ceftriaxone, or Piperacillin/Tazobactam), or a Carbapenem. After the patient is stable and able to tolerate PO medications, step down to oral antibiotics based on the C&S. If the patient is at risk for a Pseudomonas infection or has a documented Pseudomonas infection, consider Piperacillin/Tazobactam or Meropenem +/- an aminoglycoside.

Impetigo- Common Bacteria, Presentation

Impetigo is a superficial skin infection that is very common in children. It presents as a blister-like rash that can be found anywhere on the skin, but usually around the nose, mouth, hands, and arms. The blisters produce a thick, yellowish clear fluid that dries and forms honey-colors crusts over the area. The common causes of Impetigo are Streptococci spp., and Staphylococci aureus (most often MSSA).

Infective Endocarditis- Treatment Duration

In general, 4-6 weeks of IV antibiotics are required. When prosthetic valves and/or more resistant organisms are involved, treatment durations are at the upper end of this range or longer. The duration of Gentamicin synergy varies from 2-6 weeks, depending on the organism being treated and the presence or absence of a prosthetic valve.

Acute Uncomplicated UTI- Alternative Options

In patients where the primary treatment options are not optimal (either due to CrCl, sulfa allergy, or urine culture shows resistance), patient may use these as well. 1. Beta-lactam (Amoxicillin/Clavulanate or a Cephalosporin) for 3 to 7 days 2. Ciprofloxacin 250 mg PO BID (or ER 500 mg PO QD) for 3 days 3. Levofloxacin 250 mg PO QD for 3 days HOWEVER, Quinolones should NOT be used in children, pregnant patients, those with seizures, neuropathy, or QT prolongation risk. Watch for tendonitis/rupture, and BG changes (especially in patients with diabetes). If using a Quinolone, DO NOT USE Moxifloxacin or Gemifloxacin for UTIs. Moxifloxacin does not reach high enough levels in the urine and Gemifloxacin has limited activity against normal UTI pathogens.

Acute Uncomplicated Pyelonephritis- Last-Line Therapy

In patients who have no options (due to resistance, severe infection, allergies, etc.) Cefiderocol (Fetroja), a novel Cephalosporin antibiotic and Plazomicin (Zemdri), an Aminoglycoside, are approved for pyelonephritis and complicated UTIs in adults who have no other treatment options.

Complicated UTI- Last Line Therapy

In patients who have no options (due to resistance, severe infection, allergies, etc.) Cefiderocol (Fetroja), a novel Cephalosporin antibiotic and Plazomicin (Zemdri), an Aminoglycoside, are approved for pyelonephritis and complicated UTIs in adults who have no other treatment options.

Drugs of Choice- Severe SSTIs requiring IV Therapy or Hospitalization

In these conditions MRSA and Streptococci are typically needed to be covered. - Vancomycin (consider alternative if MIC 2+) - Linezolid, Tedizolid - Daptomycin - Ceftaroline - Telavancin, Oritavancin, Dalbavancin - Quinupristin/Dalfopristin, Tigecycline

C. Difficile Collateral Damage

Inactivated C Difficile spores are present in GI flora, and when an antibiotic kills off the normal flora, these spores can become activated and infectious. Activated spores produce toxins that inflame the GI mucosa, causing mild to severe symptoms. Mild symptoms of a CDI include just loose stools and some abdominal cramping. However, severe CDI can cause Pseudomembranous Colitis, which is extreme inflammation and diarrhea, to the point that it may require a colectomy and be fatal if not treated. Antibiotic regimens have in recent years become streamlined and/or discontinued to reduce CDI risk. Clindamycin is the antibiotic with the highest risk of CDI, and this should be counseled on when dispensing.

Antibiotic Selection- Infection Characteristics

Infection characteristics include the infection *site*, *severity*, and whether it is community- or hospital-acquired. Infections are that hospital-acquired often involve multi-drug resistant MDR organisms. The presence of infection is determined via the signs and symptoms. For example, bacteria in the urine does not necessarily mean there is an infection. A UTI is diagnosed based on that sign and symptoms such as dysuria, urgency, leukocytosis and/or fever.

Infective Endocarditis- Overview, Diagnosis

Infective Endocarditis is an infection of the inner tissue of the heart, typically the heart valves. Patients who have prosthetic heart valves, chronic IV access, IV drug abuse, or frequent/chronic healthcare exposure are some of those who are the most at risk. The majority of patients present with fever, with or without a heart murmur. IE is diagnosed using the Modified Duke Criteria, which includes an Echocardiogram to visualize the vegetation, and positive blood cultures. The three most common species of organisms that cause IE are Staphylococci, Streptococci, and Enterococci

Influenza- Causes, Presentation, Treatment

Influenza is caused by the Influenza virus. It is different from the common cold because it presents with a *sudden onset of fever, chills, fatigue, body aches*, dry cough, sore throat, and headache. The symptoms are more severe than a cold. Because it is a viral infection, there is no treatment with antibiotics. However, there are antivirals that can be used for influenza, BUT, the criteria is early on in the infection. The antivirals that can be used are Oseltamivir, Baloxavir, Zanamivir, or Peramivir. Typically Oseltamivir is used, BUT one must be started *within 48 hours since symptom onset*. Severe illness, such as hospitalization, or symptoms plus risk factors for complications will also be treated, regardless of time since symptom onset. During severe outbreaks patients may also start prophylactic regimens with these antivirals as well, or if they are at high risk for complications.

Complicated UTI- Severe Treatment

Initial therapy is with Ciprofloxacin or Levofloxacin, Gentamicin (+/- Ampicillin, Ceftriaxone, or Piperacillin/Tazobactam), or a Carbapenem. After the patient is stable and able to tolerate PO medications, step down to oral antibiotics based on the C&S. If the patient is at risk for a Pseudomonas infection or has a documented Pseudomonas infection, consider Piperacillin/Tazobactam or Meropenem +/- an aminoglycoside.

Preferred Active TB Regimen

Intensive Phase: 4 drugs for 2 months (until C&S is available) - RIPE: Rifampin (RIF), Isoniazid (INH), Pyrazinamide (PZA), and Ethambutol - Treatment is daily or 5x a week for 8 weeks Continuation Phase: 2 drugs for 4 months (based on C&S results) - INH and RIF, daily, 5x daily, or 3x per week for 18 weeks

Intra-abdominal Infections- Overview

Intra-abdominal infections are a common cause of hospital admission and the second most common cause of infectious mortality in the ICU. They are usually polymicrobial and can occur in any intra-abdominal organ or space. Types of infections include: - Primary, secondary, or tertiary peritonitis - Biliary tract infections (Cholecystitis, Cholangitis)

Isoniazid- Name, Dosing, Administration

Isoniazid (INH) - Available by itself (INH), or in combination with Rifampin (Rifamate), or in combination with Rifampin and Pyrazinamide (Rifater) Dosing - 5 mg/kg (max 300 mg) PO daily OR - 15 mg/kg (max 900 mg) PO 1-3x per week - *Give with Pyridoxine 25-50 mg PO daily* to reduce the risk of INH-associated peripheral neuropathy Take on an empty stomach

Assessment of Treatment for Antibiotics

It is important to monitor the patient throughout the treatment of the antibiotic. There are three major signs to monitor that let us know the patient is getting better. 1. Fever trend (and other vital signs) 2. WBC trend (shows the course of infection) 3. Reduction in signs and symptoms of infection Other clinical characteristics to monitor include: - Radiographic findings (such as chest X-ray) - If repeat cultures are negative - Decreased pain/inflammation. Markers of inflammation include pro-calcitonin levels, which are more specific for bacterial infection, C-reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR).

Latent vs Active TB

Latent TB - TB is present but does not grow in the body - No symptoms - Not contagious - Treated with 1 to 2 drugs for 3 to 4 months, preferably. - Can advance to ACTIVE TB. Active TB - Diagnosed with an Acid-fast Bacilli stain, which is not specific to MTB. A PCR or culture is needed. - Patient is symptomatic: Chest pain, Hemoptysis, Dyspnea, Chills/Shaking/Night sweats, Fatigue - Treated with RIPE (or alternatives)

Latent TB Diagnosis

Latent disease can be diagnosed using the tuberculin skin test (TST), AKA a Purified Protein Derivative test (PPD) or the Interferon Gamma Release Assay (IGRA). In the PPD, the solution is injected intradermally and the area is inspected for induration, a raised area, 48-72 hours later. A false positive TST can occur in those who have received the Bacille Calmette-Guerin vaccine, the BCG, which is used in areas of the world with high TB rates. The size of the induration that indicates a positive test is different based on the patient characteristics. The Interferon Gamma Release Assay (IGRA), a diagnostic blood test, is available and preferred over TST in some groups, especially in those who have received the BCG vaccine. The IGRA does not require a follow-up visit as well. If an IGRA is not available, the TST is acceptable.

Lefamulin- Overview

Lefamulin (Xenleta) is a first-in-class Pleuromutilin. It inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. It is available as both a tablet and an injection, and is currently only approved for CAP. It has activity against the common pathogens, including MRSA.

Drugs of Choice- Atypical Organisms

Legionella, Chlamydia, Mycoplasma, and Mycobacterium Avium Complex - Azithromycin, Clarithromycin - Doxycycline, Minocycline - Quinolones

Lipoglycopeptides- Overview

Lipoglycopeptides, typically with the suffix "-vancin," inhibit bacterial cell wall synthesis in two ways: 1. Binding to the D-alanyl-D-alanine portion of the cell wall, blocking peptidoglycan polymerization and cross-linking 2. Disrupting bacterial membrane potential and changing the cell permeability (due to the presence of a lipophilic side chain Lipoglycopeptides have *concentration-dependent* antibacterial activity and have similar coverage to Vancomycin (except for C Difficile, as these medications are IV only). Telavancin has different warnings and side effects (including a few boxed warnings) possibly due to the difference in dosing.

Lipophilic Antibiotic Properties

Lipophilic antibiotics such as the quinolones, macrolides, rifampin, linezolid and the tetracyclines have the following characteristics: - Large volume of distribution, meaning they have excellent tissue penetration, including the bone, lung and brain tissues. - Hepatic metabolism. These agents may cause hepatotoxicity, require dose adjustments in hepatic dysfunction/failure, and will probably be subject to a lot more DDIs - High intracellular concentrations, meaning they will be active against atypical (intracellular) pathogens - Sepsis clearance/distribution changes is minimal, so dose adjustments in the setting of sepsis are typically not needed - Excellent bioavailability. These agents often have IV:PO ratios of 1:1.

Lyme Disease- Organism and Treatment

Lyme Disease is caused by either Borrelia burgdorferi or Borrelia mayonii, Spirochetes. Treatment of choice is *Doxycycline 100 mg PO BID* for 10 to 21 days. Other treatment options include: - Amoxicillin 500 mg PO TID for 14 to 21 days - Cefuroxime 500 mg PO BID for 14 to 21 days

Macrolides- Overview

Macrolides bind to the 50S Ribosomal Subunit, resulting in inhibition of RNA-dependent protein synthesis. They have excellent coverage of atypicals (Legionella, Chlamydia, Mycoplasma, and Mycobacterium Avium Complex), and Haemophilus. Macrolides are treatment options for community-acquired upper and lower respiratory infections and certain sexually transmitted infections, such as chlamydia and gonorrhea, but utility against S pneumoniae, Haemophilus, Neisseria, and Moraxella can be limited due to increasing resistance.

Key Antibiotics Requiring NO Renal Adjustment

Many antibiotics are cleared through the kidney and require dose adjustments based on renal function, which includes most beta-lactams and quinolones. It is useful to know which antibiotics require NO renal adjustment. - Antistaphylococcal penicillins (Dicloxacillin, Nafcillin, Oxacillin) - Azithromycin - Ceftriaxone - Clindamycin - Doxycycline - Erythromycin - Metronidazole - Moxifloxacin - Linezolid

Preventing SSTIs

Measures to prevent bacterial skin infections include: - Wash hands often - Cover open/draining wounds with clean bandages - Avoid water, including hot tubs, swimming pools and rivers/oceans if an open wound/skin infection is present - Follow first aid measures

Meningitis- Overview and Symptoms

Meningitis is inflammation of the meninges (membranes) that cover the brain and the spinal cord. The meninges swell, causing the classic symptoms of *fever, headache, stiff neck, and altered mental status*. Other symptoms include chills, vomiting, seizures, rash, and photophobia. Meningitis symptoms MUST be quickly recognized and treated to avoid severe complications, including death.

Meningitis- Common Causes

Meningitis is most commonly caused by viral infections, but can also be due to bacteria or fungi. The risk of meningitis caused by the most common bacteria *Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae* can be decreased with vaccinations. *Listeria monocytogenes* is prevalent in select patient groups and requires additional treatment with Ampicillin. Recent surgery increases the risk of MRSA and MDR organisms, which requires different antibiotics as well.

Metronidazoles- Overview

Metronidazole (Flagyl) and its related drugs, Tinidazole (Tindamax), and Secnidazole (Solosec), are special antibiotics that work by causing a loss of helical DNA structure and strand breakage, resulting in inhibition of protein synthesis. Metronidazole has activity against Anaerobes and Protozoal infections, and is effective for bacterial vaginosis, trichomoniasis, giardiasis, amebiasis, C. difficile, and is used in combination for Intra-abdominal infections. Tinidazole is structurally related to Metronidazole, but activity is limited to protozoa (giardiasis, and amebiasis), trichomoniasis and bacterial vaginosis organisms. Secnidazole, the newest drug in this class, is only indicated for bacterial vaginosis.

Secondary Peritonitis and Cholangitis- Mild to Moderate Treatment Regimens

Mild to Moderate infections will typically be caused by PEK, anaerobes, Streptococci, +/- Enterococci - Cefoxitin - Ertapenem - Moxifloxacin - Cefazolin, Cefuroxime, or Ceftriaxone PLUS Metronidazole - Ciprofloxacin or Levofloxacin PLUS Metronidazole

Daptomycin- Monitoring and Clinical Considerations

Monitoring - CPK levels WEEKLY, and more frequently if on a statin or in those with renal impairment - Muscle pain/weakness - Signs and symptoms of neuropathy - Dyspnea Clinical Considerations - Cubicin is compatible with NS or LR (no dextrose) - Cubicin RF is compatible with NS (no dextrose), BUT it must be used only in sterile or bacteriostatic water for injection to reconstitute the lyophilized powder before it can be diluted further with NS

Carbapenems- Monitoring and Clinical Pearls

Monitoring - Renal function - Symptoms of anaphylaxis with first dose - CBC, LFTs Clinical Pearls - Imipenem is combined with cilastatin to prevent drug degradation by renal tubular dehydropeptidase - Recarbio is approved for complicated UTI/Pyelonephritis and intra-abdominal infections - Vabomere is approved for complicated UTI/Pyelonephritis ONLY - Ertapenem: *No coverage of pseudomonas, Acinetobacter, or Enterococcus* - Ertapenem: Commonly used in diabetic foot infections

Diabetic Foot Infections- Monotherapy

Monotherapy is done when MRSA coverage is not needed. However, an antibiotic is still typically chosen that has Pseudomonas coverage. - Ampicillin/sulbactam - *Piperacillin/tazobactam* - Carbapenem (*Imipenem/cilastatin, Meropenem*, Ertapenem) - Tigecycline - Moxifloxacin Bolded antibiotics cover Pseudomonas. Tigecycline is an overly broad antibiotic (covers MRSA as well), and should only be used when all other alternatives have been exhausted.

Storage Requirements: IV Antibiotics- DO NOT REFRIGERATE

Most IV medications are refrigerated, but there are a few exceptions: - Metronidazole - Moxifloxacin - SMX/TMP - Acyclovir (refrigeration causes crystallization)

Urinary Tract Infections- Overview

Most UTIs occur in the lower urinary tract, which includes the bladder (Cystitis) and the urethra. More severe infections can occur in the kidneys (Pyelonephritis) or the upper urinary tract. UTIs are more common in females than in males, as the female urethra provides a shorter route for organisms to travel up into the bladder. Sexual intercourse can facilitate this movement. Women who commonly develop UTIs after intercourse may be prescribed prophylactic antibiotics. UTIs are classified as uncomplicated or complicated, and this classification usually determines the antibiotic choice. UTIs have classic symptoms, but some patients may present asymptomatic. In these patients, a urinalysis can indicate if an infection is present.

Special Requirements: With/Without Food

Most antibiotics can be taken with food to decrease GI upset. The exceptions are either Empty Stomach or within one hour of finishing a meal. Take on an empty stomach: - Ampicillin capsules and suspension - Ceftibuten suspension - Levofloxacin solution - Penicillin VK - Rifampin - Isoniazid - Itraconazole solution - Voriconazole Take within ONE HOUR of finishing a meal: - Amoxicillin ER

Necrotizing Fasciitis- Presentation, Bacteria, Treatment

Necrotizing Fasciitis is a fast moving type of skin infection that rapidly destroys tissue and can penetrate down to the muscle, causing sepsis. It presents with intense pain/tenderness over the affected skin and underlying muscle, with reddish or purplish skin discoloration, edema, and systemic signs. Patients presenting with this should be referred for emergency treatment in a hospital with a surgical ICU. The most common bacteria that causes NF is S pyogenes (Group A Strep, GAS), but some other bacteria, like Clostridium spp. may be the culprit as well. Empiric therapy of NF is very broad. Typically *Vancomycin + Beta-lactam* (piperacillin/tazobactam, imipenem/cilastatin, or meropenem) is used.

Nitrofurantoin- Overview

Nitrofurantoin (commonly Macrobid or Macrodantin) is a bacterial cell wall inhibitor that is used for uncomplicated UTI (cystitis only). It covers E Coli, Klebsiella, Enterobacter, S Aureus, and VRE. It is the drug of choice for uncomplicated UTI. The dosing of Nitrofurantoin is different based on what brand name is, due to the salt forms. Macrobid dissolves more slowly, and therefore is given twice daily whereas Macrodantin is given four times a day.

Cephalosporins- Contraindications

No serious contraindication except for *Ceftriaxone*. - Ceftriaxone is contraindicated in hyperbilirubinemic neonates (causes biliary sludging and kernicterus). - Ceftriaxone is also contraindicated in neonates 28 days or younger used concurrently with calcium-containing IV products

HAP/VAP Pathogens and Treatment Overview

Nosocomial pathogens are the most common causes of HAP/VAP. These include MRSA, and MDR Gram-Negative Rods, which include P aeruginosa, Acinetobacter spp., Enterobacter spp., E coli, and Klebsiella spp. The degree of risk with regards to MRSA or MDR Pathogens helps to guide empiric treatment of HAP/VAP, and can end up being a total of three antibiotics, if necessary. Treatment is typically for 7 days, but shorter or longer treatment durations may be indicated based on clinical, radiologic, and laboratory parameters.

Cellulitis- Treatment

Oral antibiotics are used that must be active against Streptococci (+/- MSSA). - *Cephalexin 500mg* PO QID - Clindamycin 300mg PO QID (if beta-lactam allergy)' Other antibiotics that cover Streptococcus can be used as well, such as Penicillin VK, or Dicloxacillin. The duration of therapy is 5 days, but can be longer if there is no improvement within 5 days. Moderate to severe infections require IV treatment.

Infective Endocarditis- Dental Prophylaxis Regimens

Oral: - Amoxicillin 2 grams, 30-60 minutes before dental procedure Oral (Beta-lactam Allergy): - Cephalexin or Cefadroxil 2 grams (do not use in patients with a history of anaphylaxis, angioedema, or urticaria with penicillins) - Clindamycin 600 mg - Azithromycin or Clarithromycin 500 mg If unable to take oral medication: - Ampicillin 2 grams IM/IV, OR - Cefazolin 1 gram IM/IV Parenteral (Beta-lactam Allergy): - Cefazolin or Ceftriaxone 1 gram IM/IV (do not use in patients with a history of anaphylaxis, angioedema, or urticaria with penicillins) - Clindamycin 600 mg IM/IV

Outpatient CAP Treatment Algorithm

Outpatient CAP treatment requires an assessment of patient comorbidities and risk factors for drug-resistant pathogens. Patients with comorbidities or immunosuppression require broader coverage of possible drug-resistant S pneumoniae. After co-morbidities are analyzed (looking for chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancy, or asplenia), MRSA or Pseudomonas risk factors should be checked for. This includes prior respiratory isolation of either pathogen or hospitalization with receipt of parenteral antibiotics in the past 90 days. If the patient has these risk factors, they will probably be treated inpatient, and different antibiotics will be chosen. If they do not, the antibiotic choice is based on the presence of comorbidities or no comorbidities.

Oxazolidinones- Overview

Oxazolidinones, which include Linezolid and Tedizolid, bind to the 50S subunit of the bacterial ribosome, inhibiting translation and protein synthesis. They have coverage similar to Vancomycin, but ALSO cover VRE, both E Faecium and E Faecalis. Tedizolid is specifically approved for SSTI, while Linezolid has a wide range of approvals. Drugs - Linezolid (Zyvox) - Tedizolid (Sivextro)

PEK, HNPEK, CAPES, Mouth Flora

PEK - Proteus, E. Coli, Klebsiella HNPEK - Haemophilus, Neisseria, Proteus, E. Coli, Klebsiella CAPES - Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia Mouth Flora (Anaerobes) - Peptostreptococcus, Actinomyces

Antibiotic Selection- Patient Characteristics

Patient characteristics also impact antibiotic selection. These include Age, Weight, Renal/Hepatic function, Allergies, recent antibiotic use, colonization with resistant bacteria, recent environmental exposure, vaccination status, pregnancy status, immune function, and comorbid conditions.

Genital Warts- Treatment

Patients should apply the Imiquimod cream topically to the entire treatment area before bedtime and then be washed off after 8 hours. It is applied 3x a week until cleared or 16 weeks (whichever comes first). Treatment is not required if the patient is asymptomatic. Aldara is also approved for *superficial basal cell carcinoma* and actinic keratosis.

Acute Uncomplicated UTI- Other Therapies

Patients with UTIs may also add *Phenazopyridine (Pyridium) 200 mg PO TID for 2 days MAX* to relieve dysuria. This is OTC or an Rx as Azo Urinary Pain Relief or as Pyridium, respectfully. It should be *taken with 8 oz of water, with or immediately following food* to limit stomach upset. Phenazopyridine is contraindicated in patients with renal impairment or liver disease. It should also be used with caution in patients who have G6PD deficiency, as it can cause hemolytic anemia (discontinue if hemolysis occurs). It can cause headache, dizziness, stomach cramps, and can cause a *red-orange coloring of the urine and other body fluids*. This coloring can also *stain contact lenses and clothes*.

Diabetic Foot Infections

Patients with diabetes are at high risk for foot infections because of the neuropathic damage and compromised blood flow to the lower extremities. Foot infections are the most common cause of amputation. Ulcers are evaluated for the presence of inflammation and purulence, and then classified by severity, which guides management (e.g. surgery, and/or antibiotics). Staphylococcus spp., and Streptococcus spp. are the most prominent pathogens in diabetic foot infections, but, these infections can be *polymicrobial*, so broad-spectrum empiric therapy is usually necessary. Cultures should be performed in order to narrow therapy whenever possible. Knowledge of antibiotics that cover common MDR pathogens (e.g. MRSA, Pseudomonas) and anaerobic organisms is important for identifying appropriate therapy. It is imperative that patients follow *proper foot care* and evaluation, in order to prevent these infections. If a deeper infection is present, such as *osteomyelitis*, longer courses of antibiotics, often IV, are required.

Neurosyphilis- Treatment

Patients with neurosyphilis are treated with Penicillin G Aqueous Crystalline, 18-24 million units daily divided into 6 doses (every 4 hours) or by continuous infusion for 10-14 days. The only alternative for patients with neurosyphilis is Penicillin G Procaine.

Penicillins

Penicillins are the largest sub-class of the beta-lactams, and within this sub-class are various subgroups and types, giving this sub-class widely variable coverage of bacteria. However, no penicillin is active against MRSA or atypical organisms. The subgroups of the penicillin class are: - Natural Penicillins - Aminopenicillins - Extended-spectrum Penicillins - Antistaphylococcal Penicillins

Pharyngitis- Causes, Presentation, Antibiotic Criteria

Pharyngitis is inflammation of the pharynx, which is the area of the throat and tonsils. It can be caused by either respiratory viruses or by S Pyogenes. It is most commonly known as Strep Throat. It often presents with a sore throat, swollen lymph nodes, and white patches on the tonsils, fever, and a headache. The key feature in strep throat vs a cold is that there is an absence of cough or runny nose. Patients will get antibiotic therapy for Pharyngitis if they have a positive rapid antigen diagnostic test (a tonsil swab) or a positive S pyogenes culture.

Key Counseling Points- Mupirocin Nasal Ointment

Place 1/2 the ointment from the tube into one nostril and the other 1/2 into the other nostril. Press the nostrils at the same time and let go. Do this many times (for about 1 minute) to spread the ointment into the nose. Wash hands after use. Can cause burning and itching in the nose.

Travelers' Diarrhea- Treatment Regimens

Preferred treatment if fever, bloody stools, pregnant, or pediatric: - Azithromycin 1,000 mg PO once OR 500 mg PO daily for 1 to 3 days If the patient does not meet any of those criteria, choose one of these: - Ciprofloxacin 750 mg PO once OR 500 mg PO BID for 3 days - Levofloxacin 500 mg PO once OR daily for 1-3 days - Ofloxacin 400 mg PO once OR BID for 3 days - Rifaximin 200 mg PO TID for 3 days

Primary Peritonitis

Primary Peritonitis, referred to as Spontaneous Bacterial Peritonitis (SBP), is an infection of the peritoneal space that often occurs in patients with liver disease (e.g. cirrhosis). The most likely pathogens are Streptococci, enteric gram-negative organisms (Proteus, E Coli, Klebsiella, or PEK) and rarely anaerobes. The drug of choice is Ceftriaxone for 5 to 7 days. Alternative treatments include Ampicillin, Gentamicin, or a Quinolone. SMX/TMP, Ofloxacin, and/or Ciprofloxacin can be used for primary and secondary prophylaxis of SBP.

HAP/VAP Treatment- Antibiotics for Pseudomonas and MRSA

Pseudomonas Antibiotics (do NOT use two beta-lactams together) - Piperacillin/Tazobactam - Cefepime, Ceftazidime, Ceftolozane/Tazobactam - Levofloxacin, Ciprofloxacin - Imipenem/Cilastatin, Meropenem - Tobramycin, Gentamicin, Amikacin (these three are ALWAYS used in combination with another antipseudomonal drug) - Colistimethate, Polymyxin B (these two are ALWAYS used in combination with another antipseudomonal drug) MRSA Antibiotics - Vancomycin - Linezolid

Sputum Purulence in ABECB

Purulent sputum is thick and often yellow or green. If sputum purulence is increased, only 1 additional symptom (increased dyspnea, or increased sputum volume) is needed to justify antibiotic therapy. Without purulent sputum, all 3 primary symptoms are needed to justify antibiotic therapy.

Pyrazinamide- Name, Dosing

Pyrazinamide (PZA) - Available by itself (PZA) or in combination with Rifampin and Isoniazid (Rifater) Dosing - 20-25 mg/kg PO daily (max daily dose varies based on weight) - CrCl <30: Extend dosing interval

Quinolones

Quinolones are antibiotics that inhibit bacterial DNA Topoisomerase IV and DNA Gyrase (Topoisomerase II) inside the bacteria. This prevents supercoiling of DNA and promotes breakage of the double-stranded DNA. Quinolones have *concentration-dependent* killing, and are broad-spectrum against a variety of gram-negative, gram-positive, and atypical organisms. However, there are some distinctions between the drugs in this class.

Quinupristin/Dalfopristin- Overview

Quinupristin/Dalfopristin (Synercid) is a Streptogramin. It binds to the 50S ribosomal subunit and inhibits protein synthesis. Synercid covers most gram-positive bacteria, including MRSA, but only ONE species of Enterococci, Enterococcus Faecium (both regular and VRE). It does NOT cover E. Faecalis. Synercid is approved for complicated SSTIs, but it is not well-tolerated. Use is typically limited to VRE Faecium infections.

RMSF- Organism and Treatment

RMSF, Rocky Mountain Spotted Fever, is caused by Richettsia rickettsii, an obligate intracellular gram-negative bacteria. Treatment is with *Doxycycline 100 mg* PO/IV twice daily for 5 to 7 days. This is also the treatment of choice in *pediatric patients*.

Antibiotic Prophylaxis- Cardiac or Vascular Surgeries

Recommend Antibiotics: - *Cefazolin*, or Cefuroxime - For procedures and/or patients where MRSA is a likely pathogen, include Vancomycin in the prophylactic regimen Beta-Lactam Allergy - Vancomycin - Clindamycin

Antibiotic Prophylaxis- Hip Fracture Repairs/Total Joint Replacements

Recommended Antibiotics - *Cefazolin* - For procedures and/or patients where MRSA is a likely pathogen, include Vancomycin in the prophylactic regimen Beta-Lactam Allergy - Vancomycin - Clindamycin

Antibiotic Prophylaxis- Colorectal or Other Surgeries Involving the Abdominal Space

Recommended Antibiotics - Cefotetan - Cefoxitin - Ampicillin/Sulbactam - Ertapenem - Metronidazole + Cefazolin OR Ceftriaxone - For procedures and/or patients where MRSA is a likely pathogen, include Vancomycin in the prophylactic regimen Beta-Lactam Allergy - Clindamycin + Aminoglycoside OR Quinolone OR Aztreonam - Metronidazole + Aminoglycoside OR Quinolone

Storage Requirements: Liquid Oral Antibiotics- Refrigeration Recommended and DO NOT REFRIGERATE

Refrigeration Recommended - Amoxicillin (improves taste) Do NOT Refrigerate - *Cefdinir* - Azithromycin - Clarithromycin (bitter taste, thickens/gels) - Doxycycline (Vibramycin) - Ciprofloxacin - Levofloxacin - Clindamycin (thickens, may crystallize) - Linezolid (Zyvox) - SMX/TMP - Acyclovir - Fluconazole - Posaconazole - Voriconazole - Nystatin

Aminoglycosides- Weight-Based Dosing

Regardless of the dosing strategy used, Aminoglycosides are dosed based on body weight. If the patient is UNDERWEIGHT (< IBW), use their total body weight for dosing. If the patient is not obese or underweight, use their ideal body weight or their total body weight for dosing (typically based on hospital protocol). If the patient is OBESE, use their adjusted body weight for dosing. The clinical definition of obesity varies. For the NAPLEX, obesity will be obvious, and may be stated in the question, indicating that adjusted body weight should be used for weight-based dosing.

Community Acquired Pneumonia- Antibiotic Regimen

Regimens for CAP are designed to provide reliable coverage of S pneumoniae and Atypical bacteria. Coverage must be considered by specific antibiotic, rather than using class trends. An example of this is *Ciprofloxacin*, which is NOT used for CAP as it does NOT have reliable coverage of S pneumoniae. Therefore Ciprofloxacin is not considered a respiratory quinolone. Duration of treatment for CAP is generally 5 to 7 days. However, the choice of the antibiotic is based on whether the patient will be treated as an outpatient or in the hospital.

Richettsial Diseases and Related Infections- Overview

Rickettsial infections are caused by a variety of bacteria that are carried by many *ticks, fleas, and lice*. The rickettsial diseases caused in humans are: - Rocky Mountain Spotted Fever - Typhus - Lyme Disease - Ehrlichiosis - Tularemia RMSF is the *most common and most fatal* of rickettsial illness in the US. Initial signs and symptoms include fever, headache, and muscle pain, followed by the development of a rash.

Rifampin- Name, Dosing, Administration

Rifampin (Rifadin) - Available by itself (Rifadin), in combo with Isoniazid (Rifamate), or in combo with Isoniazid and Pyrazinamide (Rifater) Dosing - 10 mg/kg (max 600 mg) PO daily or 2-3x a week - Dosing differs for other indications Take on an empty stomach

Rifampin Drug Interactions

Rifampin is a *potent inducer* of CYP450 1A2, 2C8, 2C9, 2C19, 3A4, and P-glycoprotein. This means it can significantly decrease the concentration and therapeutic effect of many other drugs. Some notable interactions include the serum concentrations of: - Protease Inhibitors (substitute Rifabutin) - Warfarin (a very LARGE decrease in INR is common) - Oral contraceptives (decreased efficacy, requiring additional back-up contraceptive methods) DO NOT USE Rifampin with *Apixaban, Rivaroxaban, Edoxaban, or Dabigatran*. It is very important to screen the medication profile for drug interactions with Rifampin.

Rifaximin- Overview

Rifaximin (Xifaxan) is an antibiotic structurally related to Rifampin, although it is not used for mycobacterium. Rifaximin inhibits bacterial RNA synthesis by binding to DNA-dependent RNA polymerase. It's main use is for Travelers' Diarrhea (E Coli), but it is also used off-label for C Diff infections as a second or subsequent recurrence. Rifaximin can also be used to decrease the recurrence of hepatic encephalopathy and to treat Irritable Bowl Syndrome with Diarrhea (IBS-D). The dosing of Rifaximin is different based on the indication. Like other C Diff medications, it is *not effective* for systemic infections, as there is little to no absorption. Therefore, there is no adjustments needed for renal impairment.

Bacteriuria and Pregnancy- Dangers of Therapy

SMX/TMP can cause hyperbilirubinemia and kernicterus in the newborn if used close to deliver, and Nitrofurantoin can cause hemolytic anemia in the infant. Nitrofurantoin should be avoided in the third trimester. Quinolones should be avoided due to cartilage toxicity and arthropathies.

Skin and Soft-Tissue Infections- Overview

SSTIs can involve any or all layers of the skin (epidermis, dermis, and subcutaneous fat), fascia, and muscle. SSTIs usually result from the introduction of bacteria through breaks in the skin barrier, and less frequently from an infection that spreads from the bloodstream to the skin. Minor local trauma, such as small cuts, or insect bites, can be the provoking event and can progress to a deeper infection. SSTIs can be broadly divided into infections that are superficial (impetigo, furuncles, and carbuncles), nonpurulent infections that penetrate the subcutaneous tissues (cellulitis) and purulent infections (abscesses). Each are further divided as mild, moderate, or severe, which impacts the choice of antibiotics and the route of administration (topical, PO, or IV).

Secondary Peritonitis

Secondary Peritonitis is caused by a traumatic event (e.g. ulceration, ischemia, obstruction, or surgery). Abscesses are common and should be drained, and damaged tissue may require surgery. The most likely pathogens are Streptococci, enteric Gram-negatives and anaerobes (Bacteroides fragilis). In more severe cases (critically ill patients in the ICU), coverage of Pseudomonas and CAPES organisms may be necessary.

Severe Skin and Soft Tissue Infections

Severe purulent infections or those in more complicated patients (e.g. failed initial treatment, immunocompromised) require IV antibiotics initially. Drugs that are active against MRSA should be selected. Once the patient is stable and the pathogen/s have been identified, it is often possible to transition to oral antibiotics to complete treatment. Severe SSTIs can be classified as severe abscesses/purulent infections, or Necrotizing Fasciitis. Severe purulent infections are essentially the same as mild-moderate purulent infections except they are in those who are more complicated. Necrotizing Fasciitis is a life-threatening infection that must be treated ASAP.

Linezolid- Side Effects, Monitoring, Clinical Considerations

Side Effects - Decreased platelets, Hemoglobin, WBCs - Headache - Nausea, Diarrhea - Increased LFTs Monitoring - HR, BP - Blood glucose (especially in Diabetes) - Weekly CBCs - Visual function Notes - DO NOT SHAKE SUSPENSION

Nitrofurantoin- Side Effects, Key Features

Side Effects - GI upset (take with food) - Headache, rash - Brown urine discoloration (harmless) Key Features - Drug of choice for uncomplicated UTI - Contraindicated for use when CrCl is <60 mL/min HOWEVER, this restriction is per packaging label and some sources (such as the Beer's Criteria) recommend use if CrCl >30. - Macrodantin is QID, Macrobid is BID

Other Lipoglycopeptides- Side Effects, Monitoring

Side Effects - Infusion reactions, Red Man Syndrome - N/V/D - Headache - Rash Monitoring - Signs of osteomyelitis (in Oritavancin) - LFTs, Renal function

Telavancin- Side Effects, Monitoring

Side Effects - Metallic taste - Nausea/Vomiting - Increased SCr - Foamy urine Monitoring - Renal function - Pregnancy status

Tetracyclines- Side Effects, Monitoring, Notes

Side Effects - N/V/D, Rash Monitoring - LFTs, renal function, CBC Notes - IV to PO is 1:1 (Doxycycline and Minocycline) - Tablets and capsules should be taken with 8 oz of water. - DOXYCYCLINE: Take with the 8 oz of water then make sure to sit UPRIGHT for at least 30 MINUTES after the dose to avoid esophageal irritation.

Penicillins- Side Effects, Monitoring

Side Effects - Seizures (with accumulation) - GI upset, diarrhea - Rash (including SJS/TEN) - Allergic reactions, anaphylaxis - Hemolytic anemia - Renal failure - Myelosuppression with prolonged use - Increase Liver Function Tests (LFTs) Monitoring - Renal function - Symptoms of anaphylaxis with 1st dose - CBC and LFTs with prolonged courses

Monobactams- Adverse Effects and Clinical Pearls

Side Effects - Similar to penicillins, including rash, N/V/D, and increased LFTs Clinical Pearls - Can be used in patients with a penicillin allergy

Complicated UTI- Treatment Overview

Similar treatments are used for complicated UTI as are used for pyelonephritis. If the bacteria is an ESBL-producing bacteria, use a carbapenem. Treatment duration can range from 7-14 days based on symptom relief. Treat for 7 if there is prompt symptom relief and 10 to 14 days if there is a delayed response. A urinalysis, urine, and blood cultures are required in Complicated infections. If there is a catheter in place, it should be removed and changed if possible. Treatment options again are based on moderate or severe.

Sinusitis- Causes, Presentation, Antibiotic Criteria

Sinusitis is inflammation of the sinuses. It can be due to respiratory viruses, S pneumoniae, H influenzae, and M catarrhalis. Staphylococci, Anaerobes, and Gram-negative rods can also be present in chronic sinusitis. It typically presents with *nasal congestion*, purulent nasal discharge, *facial/ear/dental pain* or pressure, *headache*, fever, and fatigue. Patients are ONLY treated with antibiotics if they have: - 10+ days of symptoms OR - 3+ days of *severe symptoms* (which include fever >102, face pain, purulent nasal discharge) OR - The patient experiences worsening symptoms after an initial improvement.

Topical Decolonization

Some patients have MRSA colonization of their nares, typically due to nasal cannula or other long-term nasal devices. The only medication that is approved for decolonization of the nares is Mupirocin (Bactroban). Mupirocin nasal ointment is available in 1 gram tubes, and to decolonize the patient is to apply 1/2 the tube into each nostril twice a day for 5 days. There are minimal side effects with Mupirocin topical. The most common ones are headache, burning, localized irritation, rhinitis, and pharyngitis.

Acute Bacterial Meningitis Empiric Therapy

Step 1: COVER THE MOST COMMON BACTERIA - Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, for most patients. - Add coverage for Listeria monocytogenes in neonates, those aged >50 years, and immunocompromised patients. Age < 1 Month (Neonates) - Ampicillin (for Listeria coverage) + Cefotaxime (NOT ceftriaxone) OR Gentamicin Age 1 Month to 50 years - Ceftriaxone OR Cefotaxime + Vancomycin Age >50 years OR Immunocompromised - Ampicillin (for Listeria coverage) + Ceftriaxone OR Cefotaxime + Vancomycin If patients have a severe penicillin allergy, use a quinolone (Moxifloxacin or Levofloxacin) + Vancomycin with or without SMX/TMP (for Listeria coverage).

Penicillin Pregnancy Puzzler- STIs

Syphilis MUST be treated during pregnancy with Penicillin. But, what if a pregnant female has syphilis AND a penicillin allergy? Per the CDC, follow these steps: 1. Confirm the allergic reaction with a skin test 2. Desensitize the patient with an approved desensitization protocol. 3. Treat with IM Penicillin G Benzathine (Bicillin L-A).

Syphilis- Overview

Syphilis is an STI that is caused by Treponema pallidum, a Spirochete. It is an insidious STI that has a very long duration of illness if left untreated, ending in brain infection and death. Within 1 year of infection it progresses through three stages: Primary, Secondary, and Early Latent. After one year or so, it progresses into Late Latent and eventually infects the brain where is causes Neurosyphilis (including ocular syphilis) and can cause Congenital Syphilis if passed onto a baby from the mother. Syphilis is diagnosed using the Rapid Plasma Reagin (RPR) or the Venereal Disease Research Lab (VDRL) blood test.

MDR Active TB

TB can be resistant to INH and/or Rifampin, and if it is resistant to both, it is considered MDR-TB. Resistant TB requires use of second-line agents and longer durations of therapy (up to 24 MONTHS). While many agents can be used, preferred drugs include Quinolones (like Moxifloxacin or Levofloxacin), or injectables (Streptomycin, Amikacin, or Kanamycin). Streptomycin given IM is an alternative to Ethambutol, but it has toxicities and resistance is increasing. In extremely drug-resistant TB (XDR-TB), Bedaquiline (Sirturo) can be used, but it has a *Boxed Warning* for QT prolongation and an increased risk of death compared to placebo. Pretomanid is FDA approved for MDR-TB or XDR-TB of the lung, in combination with Bedaquiline and Linezolid. It has many ADEs, including hepatotoxicity, peripheral neuropathy (which can be severe), optic neuropathy, myelosuppression, and QT prolongation.

Tetracyclines- Overview

Tetracyclines inhibit bacterial protein synthesis by reversibly binding to the 30S ribosomal subunit. They cover many gram-positive bacteria (Staphylococci, Streptococci, Enterococci, Nocardia, Bacillus, Propionibacterium spp.), gram-negative bacteria, including respiratory flora (Haemophilus, Moraxella, and atypicals) and other unique pathogens (e.g. spirochetes, Richettsiae, Bacillus anthracis, Treponema pallidum). Doxycycline specifically has broader indications, including respiratory tract infections (e.g. CAP), tick-borne/rickettsial diseases, spirochetes, and STIs like Gonorrhea and Chlamydia. Doxycycline is an option for the treatment of mild skin infections, caused by CA-MRSA, and VRE UTIs. Minocycline is often preferred for skin infections, including acne.

Common Cold- Causes, Presentation, Treatment

The Common Cold typically is caused by a respiratory virus, such as the Rhinovirus or a Coronavirus. It presents with *sneezing, runny nose, cough*, mucus production, sore throat, and a mild (low-grade) fever. It generally clears up in a few days. Because it is a viral infection, there is no treatment with antibiotics. Treatment is symptomatic only with OTC products such as analgesics, decongestants, cough suppressants, and antihistamines. There is NO criteria for Anti-infective treatment.

Culture and Susceptibility

The Culture and Susceptibility report (C & S) is usually available within 24-72 hours of the culture/sample. This report identifies the organism and the results of the susceptibility testing. Empiric antibiotics can then be streamlined to narrower-spectrum based on this report. On the left of the report are all the possible antibiotics that can be tested in these reports, and to the right of these antibiotics is a letter (either S, I, or R). Sometimes the report will also have the MIC of the organism, or the Minimum Inhibitory Concentration. S means the organism is Susceptible or Sensitive to the antibiotic. Any antibiotic marked S could be an effective treatment. Preferably, the narrowest-spectrum antibiotic that is marked S should be used if it adheres to guidelines. I means that is has Intermediate susceptibility, meaning it may be susceptible under certain circumstances, such as extended infusions, higher concentrations, etc. Therefore an antibiotic marked, "I" may not be the best choice. R means the organism is resistant to the antibiotic and should not be used.

Gonorrhea- Treatment

The DOC for Gonorrhea is *Ceftriaxone 500 mg IM once (<150 kg) or 1 gram IM once (150 kg or more)* OR Doxycycline 100 mg BID for 7 days. Doxycycline can be added if chlamydial infection has not been ruled out. Ceftriaxone is most effective for pharyngeal infections, BUT if Ceftriaxone is not available, Cefixime (Suprax) 400 mg PO once with Azithromycin (or Doxycycline) may be used. A test for cure in 1 week is required, however. If the patient has a severe Cephalosporin allergy, use Azithromycin (+ Gemifloxacin or Gentamicin) with a test for cure in one week.

Aminopenicillins Coverage and Drugs

The aminopenicillins cover: - Streptococci - Enterococci - Gram-positive anaerobes (like the natural penicillins) PLUS - the gram-negative bacteria Haemophilus, Neisseria, Proteus, and E. Coli (due to the addition of the amino group). - The aminopenicillins can also have a beta-lactamase inhibitor added to them for additional coverage. - Amoxicillin (Moxatag, Amoxil) - Ampicillin

Sexually Transmitted Infections- Overview

The common STIs that are treated with antibiotics are Bacterial Vaginosis, Chlamydia, Gonorrhea, Syphilis, Trichomoniasis, Herpes and HPV. The other major STI that is treated with antimicrobials is HIV/AIDS. The best way to prevent STIs is abstinence, but there are ways to decrease the rate of transmission without. Safer sex practices and education are important to prevent STIs. Condoms, both male and female, can help decrease transmission. Oral sex has a much lower risk of HIV transmission than vaginal or anal sex, but still carries a risk for Herpes, Syphilis, Hepatitis B, Gonorrhea, and HPV. The Sheer Glyde dental dam is FDA-approved for safer sex, as it has proven to be safe and effective at blocking passage of infectious organisms during oral contact. Screening and prevention counseling should be performed for timely diagnosis of STIs and prevention of complications, including cervical cancer, infertility, or transmission to partners. *Sexual partners should be treated concurrently to prevent re-infection*, except in bacterial vaginosis.

Latent TB Diagnosis- TST Positive Criteria

The criteria for a positive is based on the risk factors and characteristics of the person being tested. If the patient has had close contact with a recent TB case, has significant immunosuppression (such as HIV, or using transplant medications), then 5+ mm induration is considered positive. If the patient is a recent immigrant, an IV drug user, has moderate immunosuppression, or is a resident/employee of a "high risk" congregate setting (prison, healthcare setting), then a 10+ mm induration is considered positive. If the patient has no risk factors, then a 15+ mm induration is considered positive.

Syphilis- Treatment

The drug of choice for Syphilis depends on the stage of the infection. In primary, secondary, or in the early latent stage (<1 year duration), the DOC is *Penicillin G Benzathine (Bicillin L-A)*. It should NOT be substituted with Bicillin C-R. The dose of Bicillin L-A is *2.4 million units IM ONCE*. Alternative treatments include: - *Doxycycline 100 mg PO BID* for 14 days OR - Tetracycline 500 mg PO QID for 14 days *Pregnant patients allergic to penicillin* should be desensitized and treated with Bicillin L-A. Desensitization and administration of Penicillin G Benzathine is also recommended in *HIV-Positive* patients with a penicillin allergy and poor compliance/follow-up. Patients who have Late Latent Syphilis are still treated with Penicillin G Benzathine (Bicillin L-A), but the dose is increased to *2.4 million units IM weekly for 3 weeks* (7.2 million units total). Alternatives to this is still Doxycycline 100mg PO BID or Tetracycline 500mg PO QID, but for 28 days instead of 14.

Clostridium Difficile Infection- First Episode Treatment

The first episode of C Diff is treated based on whether it is Non-severe, Severe, or Fulminant/Complicated. Non-severe OR Severe: Vancomycin 125 mg PO QID for 10 days OR Fidaxomicin 200 mg PO BID for 10 days. If the above treatments are not available and the episode is NON-SEVERE, use Metronidazole 500 mg PO TID for 10 days. If the episode is Fulminant/Complicated, use Vancomycin 500 mg PO/NG/PR QID AND Metronidazole 500 mg IV Q8hrs.

Clostridium Difficile Infection- Treatment Categories

The guidelines recommend treatment based on whether it is a first infection or a recurrence. The criteria for treatment also includes either Non-severe, Severe, or Fulminant/Complicated Disease. Non-severe CDI is classified as a WBC <15,000 cells/mm3 AND SCr <1.5 mg/dL. Severe CDI is classified as WBC 15,000+ cells/mm3 OR SCr >1.5 mg/dL. Fulminant/Complicated disease is present when there are significant systemic toxic effects, such as hypotension, shock, ileus, or toxic megacolon.

Overview of Non-AOM Upper Respiratory Tract Infections

The majority of upper respiratory tract infections are viral and antibiotics are not beneficial. The other common types of URIs include Common Cold, Influenza, Pharyngitis, and Sinusitis. With Pharyngitis and Sinusitis, antibiotics can be used if symptoms are severe or chronic and/or if there is diagnostic evidence of a bacterial infection.

Testing for C & S

The microbiology lab at the hospital or other institution uses various methods to determine which organism is present in the sample. For example, some gram-negative bacteria (e.g. E Coli) break down lactose in a unique way that others do not (such as Pseudomonas). Lactose can be used to determine the types of bacteria that are present. Once the organism is ID'd, susceptibility testing is performed to determine which antibiotics are useful for treatment. The organism is cultured (grown on an agar plate) and exposed to various concentrations of select antibiotics. The lab ID's the MIC of each antibiotic, which is specific to each antibiotic and organism. This MIC should NOT be compared among different antibiotics. The lab compares this MIC to the susceptibility breakpoint, which is the usual drug concentration that inhibits bacterial growth (and is determined by the Clinical and Laboratory Standards Institute [CLSI]). An interpretation is made as to which drugs inhibit growth, what concentration they inhibit growth at, and which drugs do not inhibit growth.

Infective Endocarditis- Dental Prophylaxis

The mouth contains bacteria that can enter the blood during dental procedures. This bacteria can travel to the heart, where they can settle on the myocardial lining, a heart valve, or a blood vessel. IE after dental procedures is rare, but risk is increased with certain cardiac conditions. In patients who are high risk, antibiotics should be used before all dental procedures that involve manipulation of the gingival tissue (gums), the periapical region (root of the mouth) or perforation of the oral mucosa.

Natural Penicillins Coverage and Drugs

The natural penicillins are active against gram-positive cocci (streptococci and enterococci only, they do NOT cover staphylcocci) and gram-positive anaerobes (the mouth flora). They have little gram-negative activity. - Penicillin V Potassium (Pen VK) - Penicillin G Aqueous (Pfizerpen-G) - Penicillin G Benzathine (Bicillin L-A)

Monobactams

The only monobactam antibiotic available is Aztreonam (Azactam). Aztreonam has a mechanism of action similar to beta-lactams, so it inhibits bacterial cell-wall synthesis by binding to the penicillin-binding proteins (PBPs), preventing the final step of peptidoglycan synthesis in the bacterial cell walls. However, Aztreonam has a different ring structure than the beta-lactams (penicillins, cephalosporins, and carbapenems), therefore making cross-sensitivity in patients with beta-lactam allergies unlikely. Aztreonam is typically used when a beta-lactam allergy is present. Aztreonam covers many gram-negative organisms, including Pseudomonas. However, it has NO gram-positive or anaerobic activity.

Dose Optimization of Antibiotics

The pharmacodynamics of the antibiotics can help decide how the antibiotic will be dosed. There are three common dosing strategies to maximize the antibiotic efficacy against the pathogen: 1. Cmax:MIC, Concentration-dependent 2. AUC:MIC, area under the curve between the concentration and the MIC. 3. Time > MIC, Time-dependent

Clostridium Difficile Infection- Second Episode Treatment

The second episode of C Diff (first recurrence) is treated based on what the first therapy was. If Metronidazole was used for the initial episode, use Vancomycin 125 mg PO QID for 10 days. If Vancomycin was used for the initial episode, use Fidaxomicin 200 mg PO BID for 10 days. If Vancomycin OR Fidaxomicin was used for the initial episode, use a Vancomycin tapered and pulsed regimen. An example of this is 125 mg PO QID for 10 days, then BID for 1 week, then daily for 1 week, then 125 mg every 2 to 3 days for 2 to 8 weeks.

Sulfonamides- Overview

The sulfonamide antibiotic that is most commonly used is Sulfamethoxazole (SMX) in combination with Trimethoprim (TMP). SMX inhibits Dihydrofolic acid formation from para-aminobenzoic acid, which interferes with bacterial folic acid synthesis. TMP inhibits Dihydrofolic acid reduction to Tetrahydrofolate, resulting in inhibition of the folic acid pathway. SMX/TMP covers Staphylococci (including MSSA and CA-MRSA). S. pneumoniae and group A streptococci coverage is unreliable. Activity against gram negative bacteria is broad and includes Haemophilus, Proteus, E Coli, Klebsiella, Enterobacter, *Shigella, Salmonella, and Stenotrophomonas*. Coverage also includes some opportunistic pathogens such as *Nocardia, Pneumocystis, and Toxoplasmosis*. Pseudomonas, Enterococci, Atypicals, and Anaerobes are NOT COVERED.

Special Requirements: Protect From Light

These antibiotics require specific light protection or they can degrade and become nonfunctioning or unstable: - Doxycycline - Micafungin - Pentamidine

Antistaphylococcal Penicillins Coverage and Drugs

These are penicillins that specifically cover Staphylococci (only MSSA, methicillin-susceptible staphylococcus aureus) and streptococci. They lack coverage against Enterococcus, gram-negative pathogens, or anaerobes. Drugs - Nafcillin - Oxacillin - Dicloxacillin

AUC to MIC Killing

This is a dosing concept that has the goal of having the most exposure over time, or the largest area under the curve over the MIC. Common antibiotics that use AUC to MIC: - Vancomycin - Macrolides - Tetracyclines - Polymyxins The dosing strategies for this concept are variable and still being studied.

Intrinsic Antibiotic Resistance

This is antibiotic resistance that is natural to the organism. An example of intrinsic resistance is E. Coli being resistant to Vancomycin because it is too large of a molecule to penetrate the cell wall.

Enzyme Inactiviation Resistance

This is resistance due to enzymes that the bacteria can produce that breaks down the antibiotic. A very common enzyme bacteria can produce are beta-lactamases, which break down beta-lactams (e.g. penicillin). These enzymes will break down beta-lactams before the antibiotic reaches their site of activity. We have developed new beta-lactams that contain Beta-Lactamase Inhibitors (clavulanate, sulbactam, tazobactam, avibactam). These inhibitors are combined with a beta-lactam and are released first, inhibiting the bacteria beta-lactamases so the beta-lactam antibiotic can come in and reach their target site of activity. Because of this, bacteria have developed Extended-Spectrum Beta-Lactamases (ESBLs), which are beta-lactamases that can break down all penicillins and most cephalosporins. Organisms that produce ESBLs can be very difficult to kill, and serious infections involving these organism are typically treated with carbapenems or the newer cephalosporin/beta-lactamase inhibitors. However, because of the increase in carbapenem usage, there are now special multi-drug resistant (MDR) gram-negative organisms known as Carbapenem-Resistant Enterobacteriaceae (CRE). Common bacteria in this family are Klebsiella spp., and E. Coli. These bacteria are capable of breaking down all penicillins, most cephalosporins, and most carbapenems. CRE infections typically require treatment with a combination of antibiotics that include drugs such as the polymyxins, which is an older drug class with a very high risk of toxicities. There is also newer, but costly cephalosporin/beta-lactamase inhibitors that can be used on CRE, for now. The most common one used is Ceftazidime/Avibactam (Avycaz).

Selection Pressure Resistance

This is resistance that occurs when antibiotics kills off susceptible bacteria, leaving behind more resistant strains to multiply. For example, normal GI flora includes Enterococcus. When antibiotics eliminate susceptible Enterococcus, the only remaining bacteria are those Enterococci that are resistant to that antibiotic. This is how Vancomycin-Resistant Enterococcus (VRE) develops.

Tigecycline- Overview

Tigecycline (Tygacil) is a glycylcycline, and is structurally related to the Tetracyclines. It works essentially the same way, by binding to the 30S ribosomal subunit of the bacteria, inhibiting protein synthesis. Tigecycline has *broad-spectrum* activity against gram-positive bacteria, including MRSA, and VRE, plus gram-negative bacteria, anaerobes, and atypical organisms. However, among the gram-negatives, it has NO activity against the three "P's," Pseudomonas, Proteus, and Providencia. Tigecycline is approved for complicated SSTIs, Intra-abdominal Infections, and CAP, but use is limited due to and increased risk of death when used (black box warning). Use is only when there are no other alternative treatments available.

Travelers' Diarrhea- Overview

Travelers' Diarrhea (TD) is a common travel-related illness and is primarily caused by ingestion of contaminated food and water. *Escherichia coli* causes 80-90% of TD cases, but may also be caused by *Campylobacter jejuni, Shigella spp., and Salmonella spp*. Viral causes can be multiple, but the common implicated viruses are *norovirus and rotavirus*. Patients typically present with a sudden onset of symptoms, including loose stools, abdominal cramps/pain, fever, vomiting, and/or *dysentery (bloody diarrhea)*. These symptoms limit traveler activity.

Acute Otitis Media- Treatment Failure Therapies and Dosing

Treatment Failure (if symptoms NOT improved after 48-72 hours of initial treatment): - Amoxicillin/Clavulanate: 90 mg/kg/day of Amoxicillin and 6.4 mg/kg/day of Clavulanate in 2 divided doses - Ceftriaxone 50 mg/kg IM/IV daily for 3 days

Inpatient CAP Treatment Algorithm

Treatment for patients who are ill enough to require hospitalization for CAP is more complex. Selection of an empiric regimen is based on the severity of illness and often includes IV antibiotics initially. Treatment is split into Non-severe and Severe. Non-severe is typically those that do not require ICU care whereas Severe is when the patient is in the ICU. Patients will be treated inpatient if they have any risk factors for Pseudomonas and/or MRSA, just to be on the safe side, which will also change the antibiotics that are chosen for treatment.

Diabetic Foot Infections- Treatment

Treatment is based on if MRSA or Pseudomonas coverage is needed. Monotherapy is when no MRSA coverage is needed, which may mean that Pseudomonas coverage is needed, but at least not MRSA. Combination therapy is used when both MRSA and Pseudomonas coverage is needed. The duration of therapy is 7-14 days with more severe, deep tissue infections needing 2-4 weeks of therapy. Severe, limb-threatening or bone/joint infections need 4-6 weeks of therapy. If osteomyelitis is present, very long courses of therapy over 6 weeks are needed, and may also require chronic, suppressive therapy.

Intra-abdominal Infections- Treatment Overview

Treatment of intra-abdominal infections, with the exception of Primary Peritonitis, consists of selecting one or more antibiotics that will cover the likely pathogens, including anaerobes. This is accomplished with a single drug in some cases, but if the antibiotic does not have anaerobic coverage, an additional antibiotic (usually *Metronidazole*) must be added. Duration of treatment is 4-7 days for mild to moderate cases and 7-14 days in more severe cases. If an intra-abdominal abscess is present, 14+ days of treatment may be required.

Latent TB Treatment Overview

Treatment of latent TB with one of the following regimens greatly reduces the risk of developing active disease. There are advantages and disadvantages of each regimen, but in general, *shorter regimens* (3-4 months) are preferred due to higher completion rates and less risk of hepatotoxicity compared to the longer courses of Isoniazid (INH).

Clostridium Difficile Infection- Treatment Overview

Treatment recommendations vary based on whether it is the *first infection or a recurrence*. Review the profile to determine the recommended treatment. Probiotics are NOT beneficial for treatment, but may be helpful for prophylaxis. If CDI is suspected (e.g. multiple loose stools), discontinue antibiotics ASAP and isolate the patient in a single room with a dedicated bathroom. Contact precautions should be taken (e.g. use PPE, so gowns and gloves). After patient care/visits, wash hands with soap and water (DO NOT USE alcohol-based hand sanitizers as the alcohol does not penetrate the spores and kill them). Diagnose C Diff ASAP using a C Difficile stool toxin test, or a culture. The C Diff toxin test is an enzyme immunoassay combined with a glutamate dehydrogenase test. It is important to NOT USE anti-diarrheal medication (such as Pepto-Bismol, Immodium, Lomotil). Only start CDI antibiotics, which can be PO Vancomycin, Metronidazole, or Fidaxomicin (Dificid).

Trichomoniasis- Overview, Treatment

Trichomoniasis is caused by Trichomonas vaginalis, a flagellated protozoan. It causes a yellow/green frothy vaginal discharge plus soreness/pain with intercourse. It is a female-only STI. Treatment is typically with *metronidazole 2 grams PO once* or Tinidazole 2 grams PO once. Metronidazole may also be given 500 mg PO BID for 7 days as an alternative. If the patient is pregnant, metronidazole is *still recommended per the CDC*. Per the package labeling, metronidazole is CI'd in the 1st trimester, but based on additional safety data, the CDC recommends metronidazole in ALL trimesters of pregnancy.

Tuberculosis- Overview

Tuberculosis, TB, is caused by Mycobacterium tuberculosis, an aerobic, non-spore forming bacillus. It primarily infects the lungs, but can disseminate to other organs. TB can be fatal if not treated properly. TB infection has two phases: Latent and Active. Latent disease is when the immune system is able to contain the infection and the patient lacks symptoms. Active pulmonary TB is extremely symptomatic and highly contagious. It most often presents with cough/hemoptysis (coughing up blood), purulent sputum, fever, and night sweats. Active TB is spread very easily through aerosolized droplets (through sneezing, coughing, talking). Hospitalized patients with active TB are isolated in a single negative pressure room. Healthcare workers caring for an Active TB patient MUST wear a respirator mask (such as an N95 face mask).

Tularemia- Organism and Treatment

Tularemia is caused by Francisella tularensis, an aerobic gram-negative coccobacilli. Treatment is with either Gentamicin or Tobramycin 5 mg/kg/day IV divided q8hrs for 7 to 14 days.

Typhus- Organism and Treatment

Typhus is caused by Rickettsia typhi, an obligate intracellular gram-negative bacteria. Treatment is with Doxycycline 100 mg PO/IV for 7 days.

Urinary Tract Infections- Diagnosis

UTI symptoms are typically used to diagnose a UTI, but patients may be asymptomatic. In these cases, or cases where cultures are to be obtained, a urinalysis is done. A urinalysis is considered positive when there is evidence of pyuria (positive leukocyte esterase or >10 WBC/mm3) and bacteriuria (10^5+ bacteria/mL in asymptomatic patients, 10^3+ bacteria/mL in symptomatic males, and 10^2+ bacteria/mL in symptomatic females or catheterized patients).

Complicated vs. Uncomplicated UTI

UTIs are classified as complicated or uncomplicated. Uncomplicated UTIs are those that occur in *non-pregnant*, premenopausal women who have no urologic abnormalities or comorbidities. An infection in males is considered to be complicated because it is likely due to some type of abnormality or obstruction, such as an enlarged prostate. Complicated infections can also result from a neurogenic bladder (e.g. spinal cord injury, stroke, MS), an obstruction (e.g. a stone), or the presence of an indwelling catheter. All patients with catheters are at risk for catheter-associated infections.

Impetigo- Treatment

Use warm, wet compresses to help remove dried crusts. Apply a topical antibiotic, typically *Mupirocin* (Bactroban). Retapamulin (Altabax) and Ozenoxacin (Xepi) are new, alternative treatments approved for impetigo and can work as well. However, if there are numerous lesions, systemic antibiotics that cover MSSA are typically necessary. Use *Cephalexin* 250 mg PO QID.

Aminoglycosides- Warnings

Use with caution in patients with impaired renal function, in the elderly, and those taking nephrotoxic medications. Examples of nephrotoxic medications include: - Amphotericin B - Cisplatin - Polymyxins - Cyclosporine - Loop Diuretics - NSAIDs - Radiocontrast Dye - Tacrolimus - Vancomycin

Tedizolid- Warnings and Side Effects

Warnings - Consider an alternate treatment in patients with neutropenia - There are NO contraindications related to MAOIs Side Effects - Nausea, diarrhea - Paresthesias - Hypertension - Visual impairment, blurry vision - Overall there are less GI side effects and myelosuppression compared to Linezolid

Colistimethate Sodium- Warnings and Clinical Considerations

Warnings - DOSE-DEPENDENT NEPHROTOXICITY, monitor renal function and electrolytes - Neurotoxicity (dizziness, headache, tingling, oral paresthesia, vertigo are all common signs/symptoms) Clinical Considerations - Be careful with the dosing on the packaging, as Colistimethate is a prodrug that is converted to Colistin. The dose can be expressed in three different ways: units of base drug, mg of base drug, and mg of Colistin base activity. - Avoid use with other nephrotoxic medications - Neurotoxicity can result in respiratory paralysis from neuromuscular blockade

Perioperative Antibiotic Prophylaxis

When a surgeon cuts into the skin during an operative/surgical procedure, organisms that live on the surface of the skin (primarily Staphylococci and Streptococci) can cause an infection. IV antibiotics are given prior to surgery to reduce this risk. The start time for antibiotics is important to achieve adequate tissue penetration at the start of the surgery. If the antibiotic is a quinolone or vancomycin, the start of the infusion is 120 minutes before the incision (start of the surgery). Essentially any other antibiotic is given 60 minutes before the incision (start of surgery). Antibiotics are usually not needed after the initial antibiotic prior to surgery. An intra-operative antibiotic is given if the surgery is >3 to 4 hours in duration, or if there is any major blood loss during the surgery. If post-operative antibiotics are needed, their use should be discontinued within 24 hours.

Aminoglycosides- Traditional Dosing Target Peaks and Troughs

When peaks and trough levels are drawn with the 4th aminoglycoside dose, the levels are compared to the goal peaks and troughs to determine if dose adjustments are needed. When dosing based on the MIC, peak goals are typically 10+ times the MIC of the bacteria causing infection. Typical goal peaks and troughs are: - Gentamicin Gram-Positive: Peak of 3-4 mcg/mL, Trough of <1 mcg/mL (due to synergy) - Gentamicin Gram-Negative: Peak of 5-10 mcg/mL, Trough of *<2 mcg/mL* - Tobramycin: Peak of 5-10 mcg/mL, Trough of *2 mcg/mL* - Amikacin: Peak of 20-30 mcg/mL, Trough of <5 mcg/mL

Aminoglycosides- Extended Interval Dosing Nomograms

With the extended-interval dosing, a random level is drawn after the first dose with the timing dependent on the type of nomogram. The Hartford Nomogram, commonly used, uses a window of 6-14 hours after the start of the infusion. This nomogram is used to plot the patient's level and determine the appropriate dosing interval. If the level plots on a line, round UP to the next dosing interval to avoid potential toxicity.