midterm nr568

If someone is allergic to one antibiotic group, which do you prescribe in its place? 1. If the PCN allergy is mild, a 2. If the PCN allergy is severe, 3. If a pt has a Sulfa allergy what do you prescribe?

1. a cephalosporin is often an appropriate alternative 2. vancomycin, erythromycin, and clindamycin are effective and safe alternatives; AVOID carbapenems 3. Nitrofurantoin

Patient education for Nitrofurantoin 1. most adverse reactions are GI (anorexia, nausea, vomiting, diarrhea). These can be minimized by 2. Early symptoms of Peripheral neuropathy include: 3. Detecting acute pulmonary injury: 4. Inform pregnant women about risk birth defects and to avoid use 5. Severe liver damage may manifest as

1. administering nitrofurantoin with milk or with meals, 2. muscle weakness, tingling sensations, and numbness. Patients should report them immediately 3. Instruct pts to report: dyspnea, chest pain, chills, fever, cough; if present stop tx 4. especially in 3rd trimester 5. as hepatitis, cholestatic jaundice, and hepatic necrosis

Monitoring needs Macrolides 1. There is no Patient education 2. GI disturbances (epigastric pain, nausea, vomiting, diarrhea) are the most common side effects; These can be reduced by

1. baseline or routine monitoring required 2. administering with meals but should only be with acid stable formulations-enteric-coated

Onychomycosis (infection of toenails) 1. Onychomycosis is difficult to eradicate and requires prolonged treatment. Infections may be caused by (blank) or (blank) 2. Onychomycosis may be treated with

1. by dermatophytes or Candida species. 2. oral allylamine/azole (terbinafine and itraconazole both are active against Candida species and dermatophytes) OR with topical ciclopirox-only active against dermatophyte

Monitoring needs with Fluoroquinolones 1. Although no routine or baseline

1. monitoring is listed in book; Levofloxacin needs reduction if GFR is <50ml/min

Patient Education-Sulfonamides 1. Encourage hydration; pts should drink at least 2. To prevent photosensitivity reactions, advise patients 3. Pts should be instructed to observe for alterations that may indicate

1. 8-10 glasses of water/noncaffeinated fluids per day to decrease the risk for crystalluria. 2. to avoid prolonged exposure to sunlight, wear protective clothing, apply sunscreen, avoid tanning beds 3. hypersensitivity (esp with topical agents) (e.g., rash) and to report these promptly if they occur.

Superficial Infections: 1. The superficial mycoses are caused by two groups of organisms 2. Dermatophytoses are generally confined to the

1. Candida species and dermatophytes-ie, ringworm 2. skin, hair, and nails. dermatophytes are more common than superficial infections with Candida

Indications for use of Cephalosporins 1. First-generation-Cephalexin (Keflex) 2. Second generation-cefoxitin (Mefoxin) 3. Third-generation cefotaxime 4. Fourth generation cefepime (Maxipime)​ 5. ceftaroline (Teflaro)

1. narrow spectrum, skin, soft tissue infections, used for Gram + S. Aureus/epidermidis/streptococci, used as an alternative in pts with a mild PCN allergy, surgical prophylaxis 2. broader spectrum, otitis, sinusitis, respiratory tract, Klebsiella, E. coli Gr+ /Gr- 3. more resistant to β-lactamases; meningitis, gram - nosocomial infections 4. narrow spectrum-HAP and resistant pseudomonas​ 5. narrow spectrum; MRSA infections​

1. Systemic mycoses can be subdivided into two categories: 2. The opportunistic mycoses include— 3. nonopportunistic infections include . Treating systemic mycoses can be difficult; may require prolonged therapy with drugs that frequently prove toxic.

1. opportunistic infections and nonopportunistic infections. 2. candidiasis, aspergillosis, cryptococcosis, and mucormycosis—are seen primarily in debilitated or immunocompromised hosts 3. sporotrichosis, blastomycosis, histoplasmosis, and coccidioidomycosis; can occur in any host & are relatively uncommon

Treatment of C. Diff 1. Initial episode: mild or moderate 2. Initial episode: fulminant-characterized by shock, megacolon, or hypotension— 3. Alternative tx

1. oral vancomycin or fidaxomicin-a narrow spectrum macrolide 2. oral vancomycin is preferred. 3. Metronidazole can be used in situations where oral vancomycin or fidaxomicin is not available

Monitoring needs for Nitrofurantoin 1. Routine monitoring: None was listed in book but should undergo 2. Baseline Data

1. renal and liver fxn tests for in pts w/ liver impairment 2. Renal function, urinalysis with culture

Contraindications and high-risk patients Vancomycin-Glycopeptide 1. In patients with 2. Black Box Warning of Telavancin (Glycopeptide)

1. renal impairment, dosage must be reduced 2. when used to tx HAP/VAP in patients with a Cr clearance of less than 50 mL/min has been associated with increased mortality • can prolong the QT intervals • Contraindicated in pregnancy

Indications for use Tetracyclines 1. broad-spectrum abx with a variety of uses

1. rickettsial diseases, 2. Chlamydia trachomatis infections, (3) brucellosis; (4) cholera; (5) pneumonia caused by Mycoplasma pneumoniae; (6) Lyme disease; (7) anthrax; (8) gastric infection with H. pylori 9. severe acne vulgaris

Patient Education with Fluoroquinolones 1. fluoroquinolones should be discontinued at the first 2. fluoroquinolones pose a risk for phototoxicity

1. sign of tendon pain, swelling, or inflammation• In addition, patients should refrain from exercise until tendinitis has been ruled out 2. (severe sunburn), characterized by burning, erythema, blistering, and edema. • This can occur even if sunscreen has been applied.• • Drug should be withdrawn at the first sign of a phototoxic reaction (e.g., burning sensation, redness, rash)

Indications for use Clindamycin-Lincosamides 1. DOC for severe group A 2. widely as an alternative

1. streptococcal infection and for gas gangrene & anaerobic infections outside the CNS 2. to penicillin b/c its effective against gram + cocci

MOA of Fluoroquinolones

Benefits derive from disrupting DNA replication/cell division; Fluoroquinolones DO NOT disrupt synthesis of proteins or the cell wall • fluoroquinolones are broad-spectrum agents;

- Understand broad spectrum vs narrow spectrum agents Broad-Spectrum: 1. Targets wider number of bacteria types. Acts on both 2. Commonly used against 3. Commonly used for (blank) therapy; when the pathogen is unknown or 4. A major con is disruption of Narrow-Spectrum: 1. Effective against a specific 2. Used when infecting pathogens

Broad-Spectrum: 1. gram- and gram + organisms 2. H. influenzae, E. coli, Proteus mirabilis, enterococci, N. gonorrhoeae 3. empiric; infection with multiple types of bacteria is suspected. 4. native bacteria and the development of antimicrobial resistance Narrow-Spectrum: 1. bacteria type 2. is known

Broad spectrum vs narrow spectrum

Broad-spectrum - Broad-spectrum penicillins: ampicillin and others - Extended-spectrum penicillins: piperacillin and others - Cephalosporins (third generation) - Tetracyclines: tetracycline and others - Carbapenems: imipenem and others - Trimethoprim - Sulfonamides: sulfisoxazole and others - Fluoroquinolones: ciprofloxacin and others narrow-spectrum - Penicillin G and V - Penicillinase-resistant penicillins: oxacillin and nafcillin - Vancomycin - Erythromycin - Clindamycin - Aminoglycosides: gentamicin and others - Cephalosporins (first and second generations) - Isoniazid - Rifampin - Ethambutol - Pyrazinamide

Clostridiodies difficile Infection-another section • Causes/Transmission

Causes/Transmission • CDI is almost always preceded by the use of abx, which kill off normal gut flora and allow C. diff. to flourish. • Antibiotics most likely to promote CDI are clindamycin, second- and third-generation cephalosporins, and fluoroquinolones

Patient-Centered Care Across the Life Span-Tetracyclines Children/adolescents • Tetracyclines should not be used in children younger than Pregnant women • Animal studies reveal that tetracyclines can cause Breastfeeding women • Use of tetracyclines during tooth development can cause Older adults • Tetracyclines can interact with drugs, including

Children/adolescents • 8 years because they may cause permanent discoloration of the teeth. Pregnant women • fetal harm in pregnancy. Thus this class of drugs should be avoided in pregnant women. Breastfeeding women • permanent staining. Tetracyclines should be avoided by breastfeeding women. Older adults • digoxin. & many medications, check for interactions.

Patient-Centered Care Across the Life Span-Fluoroquinolones Children/adolescents • (blank & blank) are the only Pregnancy • Although data reveal little potential for fluoroquinolone toxicity in the fetus, Breastfeeding women • Effects of fluoroquinolones on the nursing infant are largely Older adults • Fluoroquinolones are generally well tolerated in older adults.

Children/adolescents • Ciprofloxacin and levofloxacin; fluoros approved for use in children. Because of concerns of tendon injury, fluoros are generally avoided in this population. Pregnancy • flouros are generally avoided Breastfeeding women • unknown. Other medications should be considered if possible. Older adults • For safe dosing, creatinine clearance should be calculated

Itraconazole-Azole ○ clinical uses ○ MOA

Clinical Uses ○ is an alternative to amphotericin B for systemic mycoses and is the prototype for azole family. ○ also used in the oral tx of Onychomycosis-nail fungus MOA ○ itraconazole inhibits the synthesis of ergosterol, an essential component of the fungal cytoplasmic membrane. The result is leakage of cellular components

Which antibiotics require renal dose adjustments? Agents that must be reduced in renal impairment Fluoroquinolones Macrolides Antimetabolites Glycopeptides

Fluoroquinolones - Ciprofloxacin Reduce to 50-75% if GFR<50 ml/min - Levofloxacin Reduce if GFR<50 ml/min; Avoid if GFR<10 ml/min Macrolides - Clarithromycin Reduce by 50% if GFR<30 ml/min Antimetabolites - TMP-SMZ,( Bactrim) Reduce to 50% if GFR <30 ml/min Avoid if GFR<15 ml/min Glycopeptides - Vancomycin Adjust based on drug level&Cr Clearance

Mechanism of Action Macrolides

Protein synthesis inhibition: erythromycin binds to the 50S ribosomal subunit • The drug is usually bacteriostatic but can be bactericidal against highly susceptible organisms or when present in high concentrations

MOA for Clindamycin

- Clindamycin is usually bacteriostatic • Clindamycin binds to the 50S subunit of bacterial ribosomes and thereby inhibits protein synthesis

Which antibiotics require renal dose adjustments? Agents to avoid in severe Chronic Kidney Disease

- Penicillin G (Myoclonus, Seizures, coma risk) - Imipenem (Seizure risk); Meropenem safe - Tetracycline (Uremia); Doxycycline safe - Nitrofurantoin (peripheral neurotoxicity) - Aminoglycosides (close monitoring if used)

Know how to treat Different types of Oral candidiasis, also known as thrush, is seen often.

- Topical agents—nystatin, clotrimazole, and miconazole—are generally effective. • In the immunocompromised host, oral therapy with fluconazole or ketoconazole is usually required.

Cephalosporins MOA

- disrupt cell wall synthesis - are bactericidal, often resistant to β-lactamases

Patient Education for Tetracyclines 1. Sun Exposure Risk With Tetracyclines-

1. All tetracyclines can increase the sensitivity of the skin to UV light resulting in sunburn. Advise patients to avoid prolonged exposure to sunlight, to wear protective clothing, and to apply sunscreen to exposed skin

Monitoring needs for Aminoglycosides 1. Baseline Data 2. Monitoring: 3. Provider monitoring

1. Blood and/or urine cultures. 2. Aminoglycoside levels (peaks-to have sufficient killl levels, and troughs-to prevent ototoxicity) and renal function must be monitored. 3. The first sign of impending cochlear damage (tinnitus, persistent headache, or both).

Contraindications and high-risk patients Clindamycin-Lincosamides 1. Black Box Warning: Clindamycin can cause potentially fatal

1. C. difficile assoc diarrhea (CDAD)- characterized by profuse, watery diarrhea (10 to 20 watery stools per day)

Contraindications and high-risk patients Cephalosporins 1. the Main risk with cephalosporins is 2. Cephalosporins have been reported with type I allergic reactions 3. Contraindicated for 4. Caution is needed if these drugs are combined with other bleeding agents

1. C. difficile infection 2. serum sickness-like reactions, and other skin rashes, arthralgia, and fever 3. pts with severe PCN allergy or Ceph allergy 4. (anticoags, NSAIDS, thrombolytic) they can interfere with Vit K

Indications for use Vancomycin-Glycopeptide 1. Principal indications are 2. MOA 3. indications for using Telavancin (Glycopeptide)

1. C. difficile infection, MRSA infection, or allergy to PCN 2. vancomycin inhibits cell wall synthesis 3. treating vancomycin-resistant infections;

Classification of Antimicrobial Drugs • There are two main classification schemes

1. Classification by Susceptible Organism Antibacterial Drugs • Narrow Spectrum-Gram+ cocci/bacilli, Gram- aerobes, M. tuberculosis • Broad Spectrum-Gram+ cocci and gram- bacilli Antiviral Drugs • Drugs for HIV infection • Drugs for influenza • Other antiviral drugs-acycolvir Antifungal Drugs-amphotericin B; Azoles 2. Classification by Mechanism of Action • Inhibitors of cell wall synthesis • Drugs that disrupt the cell membrane • Bactericidal inhibitors of protein synthesis • Bacteriostatic inhibitors of protein synthesis • Drugs that interfere with synthesis or integrity of bacterial DNA and RNA • Antimetabolites • Drugs that suppress viral replication

Community-Acquired Pneumonia (CAP) Treatment options 1. If pt HAS comorbidities: ETOH; CHF; heart/lung/liver/kidney disease; abx in the last three months; diabetes; splenectomy/asplenia or high rates (>25%) of macrolide-resistant S. pneumoniae 2. What other drug class can be used for high Antimicrobial Resistance

1. Combination therapy (beta-lactam + macrolide) ○ Amoxicillin/clavulanate (Augmentin) 1,000mg/62.5mg PO BID -or- Cephalosporin cefpodoxime or Ceph-cefuroxime + azithromycin (Z-pack) or clarithromycin 2. Respiratory fluoroquinolone; duration 5-7 days ○ Moxifloxacin ○ Gemifloxacin

Know how to treat Different types of ○ tinea pedis (ringworm of the foot, or "athlete's foot"), 1. Is the most 2. generally responds well to

1. Common fungal infection 2. topical allylamine ■ Terbinafine, Butenafine

Community-Acquired Pneumonia (CAP) Treatment options for Typical pneumonia 1. If pt has NO comorbidities: 2. What other class can be used for penicillin-sensitive S. pneumoniae 3. If those therapies FAIL and a resistant organism is suspected

1. First-line agents: Beta-lactam or doxycycline ○ Amoxicillin 1,000 mg PO TID x 5-7 days OR ○ Doxycycline 100mg PO BID x 5-7 days ● Alternative: Macrolides ○ Azithromycin (Z-pack) daily x 5 days ○ Clarithromycin 2. Linezolid (Zyvox) 3. the use of respiratory fluoroquinolones active against S. pneumoniae is warranted

Adverse reactions/High-Risk Patients • Adverse effects 1. Common ones are 2. Black Box Warning 3. Drug Interactions 3a. Avoid use with drugs metabolized by CYP3A4 3b. (blank drugs) can greatly reduce the absorption of oral itraconazole.

1. GI reactions (nausea, vomiting, diarrhea) are most common. Other reactions include rash, headache, abdominal pain, and edema (pg. 716). ○ serious effects: cardiac suppression and liver injury 2. Negative Inotropic Actions: can cause a transient decrease in ventricular EF%, should not be used for in pts with HF, a hx HF, or other indications of ventricular dysfxn 3a. (warfarin, dofetilide-Tikosin, cyclosporine, digoxin, quinidine-antiarrhythmic . 3b. Drugs that decrease gastric acidity—antacids, H2 antagonists, and PPIs— ○ administer at least 1 hour before itraconazole or 2 hours after

Penicillins-Examples 1. Narrow-spectrum PCNs (penicillinase sensitive) 2. Narrow-spectrum penicillins: (penicillinase-resistant) 3. Broad-spectrum penicillins (aminopenicillins) 4. Extended-Spectrum Penicillins (Antipseudomonal Penicillins)

1. Penicillin G, Penicillin V 2. Nafcillin, Oxacillin, Dicloxacillin 3. Ampicillin, Amoxicillin 4. piperacillin

Patient-Centered Care Across the Life Span-Antimicrobials 1. Infants Infants are highly vulnerable to drug toxicity. Because of 2. Children/adolescents The tetracyclines are toxic b/c 3. Pregnant women Antimicrobial drugs can cross the 4. Breastfeeding women Antibiotics can enter breast milk, possibly affecting the 5. In the older adult, heightened drug sensitivity is due in large part

1. Infants • ​poorly developed kidney and liver function, neonates eliminate drugs slowly. Use of sulfonamides in newborns can produce kernicterus, a severe neurologic disorder caused by displacement of bilirubin from plasma proteins . 2. Children/adolescents • ​They bind to developing teeth, causing discoloration. 3. Pregnant women • ​placenta, posing a risk to the developing fetus. For example, when gentamicin is used during pregnancy, irreversible hearing loss in the infant may result. 4. Breastfeeding women • ​the nursing infant. ie, sulfonamides can reach levels in milk that are sufficient to cause kernicterus As a general guideline, benefits should outweigh the risks. 5. Older adults • to reduced rates of drug metabolism and drug excretion, which can result in accumulation of antibiotics to toxic levels.

Community-Acquired Pneumonia (CAP) Treatment options for Atypical Pneumonia 1. What is the 1st DOC cause by Mycobacterium Pneumoniae

1. Macrolide-Erythromycin

1. Monitoring needs for Clindamycin-Lincosamides 2. Patient education

1. Monitor for CDAD 2. Patients should promptly report any diarrhea to their health care provider.

Monitoring needs for Sulfonamides and trimethoprim 1. Monitoring for Sulfonamides 2. Monitoring for trimethoprim 3. Monitoring for both 4. Baseline Data: Establish infection:

1. Monitor renal fx for sulfas; In pts with renal impairment (Cr clearance-15-30 mL/min), dosage should be decreased by 50% 2. If hyperkalemia is suspected due to trimethoprim, K must be checked 4 days after starting treatment. 3. CBC should be monitored if the patient develops S/S of blood disorders, as should CD4+ count for patients with HIV infection; S/S of hypersensitivity reactions 4. UA (if UTI is suspected) with C&S as indicated. Obtain CBC with diff if indicated or if treatment will be prolonged. Renal function should be checked if there is concern that it may be compromised.

Contraindications and high-risk patients for Nitrofurantoin 1. Pulmonary: can induce serious pulmonary reactions: 2. Can cause hematologic reactions: 3. Can cause Peripheral neuropathy: may be irreversible; highest risk in pts with 4. Do NOT use nitrofurantoin in pts with 5. Hepatotoxicity: has caused severe liver injury, 6. Birth defects: should absolutely be avoided in pregnant

1. Most common-manifest as dyspnea, chest pain, cough-stop drug if these sx are observed 2. agranulocytosis, leukopenia, thrombocytopenia, and megaloblastic anemia; Avoid in newborns <1 mo, pregnant women near term, pts with G6PD deficiency 3. renal impairment taking nitrofurantoin chronically 4. renal impairment 5. Deaths have occurred. Patients should undergo periodic tests of liver function 6. women near term: 38-42 weeks of gestation

1. Monitoring Carbapenems 2. Baseline Data:

1. No routine laboratory monitoring is suggested. 2. Take samples for culture to determine the identity and sensitivity of the infecting organism.

Contraindications and high-risk patients of PCNs 1. What is the main contraindication in general? 2. Penicillin G, Penicillin V 3. Ampicillin, Amoxicillin (Broad) 4. piperacillin (extended)

1. PCN allergy- it can range from a minor rash to anaphylaxis; it can decrease over time but if severe should NOT be used; if no other alternative pts can undergo skin testing but this still carries a risk 2. The next most common ADR is non-allergic rash; Probenecid (antigout med) prolongs the half-life of PCNs and increases risk for toxicity 3. rash and diarrhea are most common 4. can cause bleeding by disrupting plt function • Dosage should be reduced in patients with renal impairment

Monitoring needs for PCNs 1. Monitoring for renal impairment which can cause 2. Identifying High-Risk Patients 3. Baseline data

1. PCNs to accumulate to toxic levels. Also monitor for allergy symptoms​, C.diff diarrhea​ 2. Penicillins should NOT be used in patients with a history of severe allergic reactions to penicillins, cephalosporins, or carbapenems 3. Obtain a culture

Community-Acquired Pneumonia (CAP) - pneumonia acquired outside hospital or healthcare facilities - most often seen in primary care. Causative agents 1. Most common bacteria is 2. What other pathogens can cause CAP in the General population 3. What causes CAP in Smokers and those with COPD 4. What causes CAP in those with cystic fibrosis (CF) 5. What is the Gold Standard for CAP dx 6. What pathogen is usually transmitted by inhaling mist or aspiration liquid that comes from a water source

1. Streptococcus Pneumoniae (aka pneumococcus); gram positive; also most deadly 2. Atypical bacteria (Mycoplasma pneumoniae)-often seen in people of close proximity (correctional facilities, college dormitories, SNFs) or Viruses (influenza, RSV) 3. Haemophilus influenzae (gram-neg) 4. Pseudomonas aeruginosa (gram neg) 5. Chest x-ray 6. Legionella sp

Monitoring needs for Vancomycin-Glycopeptide 1. Baseline Data: 2. Monitoring: Vancomycin (blank) should be monitored during IV administration.

1. Take samples for culture to determine the identity and sensitivity of the infecting organism. 2. drug levels

Other ways to organize classes of Drugs - Bacteriostatic Inhibitors of Protein Synthesis include

1. Tetracycline 2. Macrolide 3. Clindamycin

Know how to treat Different types of ○ tinea capitis (ringworm of the scalp), 1. Is difficult to treat and (blank) drugs don't typically work 2. Usually responds well to

1. Topical 2. Oral griseofulvin, taken for 6 to 8 weeks, is considered standard therapy. • However, oral terbinafine, taken for only 2 to 4 weeks, may be more effective. ■ Griseofulvin, terbinafine

Indications for use Sulfonamides and trimethoprim combo is abbreviated SMZ/TMP 1. 1st line drug for Uncomplicated UTIs 2. sulfonamides are alternatives to pt's with allergies to 3. Topical sulfonamides are used to tx infections 4. TMP/SMZ is valuable for

1. Trimethoprim/sulfamethoxazole 3 days -OR- Nitrofurantoin 5 days 2. PCN, doxycycline & erythromycin 3. of the eyes and to suppress bacteria in burn patients and bacterial vaginosis caused by G. vaginalis 4. UTIs, otitis media, bronchitis

Contraindications and high-risk patients for Tetracyclines 1. Tetracyclines bind to calcium in developing teeth, 2. Hepatotoxicity-Tetracyclines can cause fatty infiltration of 3. Renal Toxicity-tetracycline and demeclocycline are 4. Drug and Food Interactions

1. causing staining of teeth of the infant; Discoloration of permanent teeth occurs when taken by children aged 4 months to 8 years; avoid in children <8 yrs 2. the liver; highest risk-Pregnant and postpartum 3. contraindicated in pts with renal impairment; doxycycline or minocycline are safe with renal impairment as they're eliminated by liver 4. Can bind with certain metal ions (calcium, iron, magnesium, aluminum, zinc) found in milk products, calcium/iron supplements, magnesium-containing laxatives, and most antacids resulting in decreased absorption

- Treatment of chlamydial pneumonia: 1. C. pneumoniae (atypical pneumonia) is more commonly seen in 2. 1st line Treatment is

1. children and young adults 2a. Macrolides Azithromycin (5 days total) 2b. Tetracycline - 250 mg orally every 6 hours for 14-21 days 2c. Doxycyclines for 10 days - Do not use doxy in pregnant women 2d. Fluoroquinolones-Levofloxacin for 7-14 days

Monitoring needs for Cephalosporins 1. In patients with renal insufficiency, 2. Baseline Data: Take samples Patient Education 3. Instruct patients to report increase in 4. cefazolin-1st gen and cefotetan—2nd gen; can induce a state of alcohol intolerance

1. dosages of most cephalosporins must be reduced 2. for culture to determine the identity and sensitivity Patient Education 3. stool frequency; All cephalosporins can promote C. difficile infection. 4. the disulfiram effect can be very dangerous pts taking these drgs should avoid alcohol

Indications for use Macrolides 1. erythromycin is the treatment of choice 2. may be used as an alternative to 3. macrolides are all considered first-line treatments 4. Like are also tetracyclines are DOC for

1. for acute diphtheria & Bordetella pertussis 2. PCNs in pts w/allergy 3. for patients with CAP who have no comorbidities or risk factors for drug-resistant pathogens 4. certain chlamydial infections (urethritis, cervicitis)

Indications for use Carbapenems 1. imipenem is the most effective beta-lactam 2. Mechanism of Action

1. for anaerobic bacteria & serious infections caused by gram-pos/neg cocci, gram-neg bacilli (broad spect) 2. Imipenem binds to two PBPs, causing weakening of the bacterial cell wall; resistant to all beta-lactamases

Contraindications and high-risk patients of Fluoroquinolones 1. Older adults are at high risk for (HINT two things) 2. Others at high risk for tendon rupture include 3. Black Box Warning: Ciprofloxacin and other fluoroquinolones can 4. These broad spectrum abx can also cause infections such as 5. Like tetracylcines Absorption can be reduced by 6. Ciprofloxacin can increase plasma levels of

1. for confusion, somnolence, psychosis, and visual disturbances; cartilage damage(tendon rupture), usually of the Achilles tendon highest risk are those >60 years, 2. those taking glucocorticoids, those with a heart, lung, or kidney transplantation 3. exacerbate muscle weakness in patients with myasthenia gravis-avoid in these pts 4. Candida infections of the pharynx and vagina may develop and C. Diff during treatment 5. compounds that have aluminum/magnesium-containing antacids, iron salts, zinc salts, sucralfate, calcium supplements, and milk and dairy 6. theophylline, warfarin, and tinidazole (an antifungal)

Indications for use Aminoglycosides ie gentamicin, tobramycin 1. Parenteral Therapy: tx of serious infections 2. Topical Therapy: is used for 3. Often given in Combination therapy with drugs that

1. from aerobic gram-neg bacilli ie: E. coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, and P. aeruginosa-common in Cystic Fibrosis 2. Gentamicin and tobramycin can treat eye infections, neomycin is for infections of ear and eye 3. weaken the cell wall-PCNs, cephs, Vanc

Patient Education for Aminoglycosides 1. hearing loss begins 2. • The first sign of impending vestibular damage is 3. Pts should be informed about the

1. in the high-frequency range then progresses to Loss of low-frequency headache, which may last for 1 or 2 days; After that, nausea, unsteadiness, dizziness, and vertigo begin to appear. 3. sx of vestibular and cochlear damage and instructed to report them

Miscellaneous Abx-Metronidazole 1. MOA 2. Clinical uses 3. Adverse effects

1. interacts with DNA to cause strand breakage of structure, inhibition of synthesis and cell death 2. used in combo with a tetracycline and bismuth subsalicylate to eradicate H. pylori in PUD; used as an alternative to vanc in tx of C. difficile infection 3. Black Box Warning: has been assoc with increased carcinogenic risk in mice and rats

Contraindications and high-risk patients Aminoglycoside 1. • Black Box Warning: All aminoglycosides can accumulate within the inner ears, causing 2. Black Box Warning: Neurotoxicity: sx may include 3. Black Box Warning: (blank) has highest risk increases in pts w/ prolonged use and with preexisting renal impairment; 3. These drugs readily cross the placenta and may be

1. irreversible injury ototoxicity that can impair both hearing and balance 2. numbness, tingling, muscle twitching, and seizures 3. Nephrotoxicity; injury to the kidneys usually reverses after aminoglycoside use is stopped; risk increased when pts are on loop diuretics, other nephrotoxic drugs and with prolonged used of aminoglycosides. 4. toxic to the fetus

Indications for use Nitrofurantoin 1. Nitrofurantoin is indicated for acute infections of the 2. can also be used for prophylaxis of 3. Can used used as an alternative for a

1. lower urinary tract (uncomplicated cystitis) NOT the upper urinary tract 2. recurrent lower UTI (called urinary antiseptics) 3. Sulfa allergy

Indications for use of PCNs 1. Penicillin G, Penicillin V (Narrow/PCN-ase S) 2. Nafcillin, Oxacillin, Dicloxacillin (Narrow/PCN-ase R) 3. Ampicillin, Amoxicillin (Broad) 4. piperacillin (extended)

1. streptococcal pharyngitis​, N. Meningitis/gonorrhoeae; active against most gram +/- cocci and spirochetes-T. pallidum 2. use for all PCN-ase R Staph infections ie: S. aureus and S. epidermidis, NOT MRSA 3. Amoxicillin-1st line for ENT/Skin/UTIs ie: AOM and sinusitis​, Amoxicillin + clavulanate first line for Severe AOM & animal/human bites, Ampicillin-1st line for infants with UTIs 4. used mainly for P. aeruginosa; often combined with β-lactamase inhibitor (Zosyn), also used for H. influenzae, E. coli, enterococci, N. gonorrhoeae,

Indications for use Fluoroquinolones ie: Cipro, ofloxacin (Floxin), levofloxacin (Levaquin) and moxifloxacin 1. approved for a variety of infections including 2. For CAP they should only be used if 3. What are preferred agents for complicated UTIs & Pyelonephritis 4. Also used as 1st line therapy for 4. This is DOC for prevention of 5. Two approved used in children

1. the respiratory tract, urinary tract, (GI) tract, bones, joints, skin, and soft tissues 2. individual has been treated with an antimicrobial agent in the last 90 days that could increase the risk of a drug-resistant microbe 3. Ciprofloxacin, levofloxacin 4. acute prostatitis 4. anthrax 5. (1) complicated UTIs/kidney infections-E. coli, (2) postexposure prophylaxis of anthrax

Contraindications and high-risk patients Macrolides 1. When erythromycin is combined with a CYP3A4 inhibitors (ie: verapamil, diltiazem, azole antifungals-ketoconazole, HIV protease inhibitors (e.g., ritonavir, saquinavir) 2. erythromycin should be avoided by patients with 3. food decreases absorption of all except erythromycin 4. As a CYP3A4 inhibitor erythromycin can raise levels of

1. there is 5x the risk for sudden cardiac death 2. congenital QT prolongation and by those taking class IA or III antidysrhythmic drugs 3. ethylsuccinate or enteric-coated formulations 4. theophylline, carbamazepine (used for szs and bipolar disorder), and warfarin

Know how to treat Different types of ○ tinea cruris (ringworm of the groin), 1. responds well to 2. Treatment should continue for 3. If the infection is severely inflamed

1. topical allylamine/azole therapy. ■ Terbinafine, Butenafine, Clotrimazole - if severe 2. at least 1 week after symptoms have cleared. 3. a systemic antifungal drug (e.g. Clotrimazole) may be needed; topical or systemic glucocorticoids may be needed as well.

Know how to treat Different types of ○ tinea corporis (ringworm of the body), 1. usually responds to a 2. Treatment should continue for 3. Severe infection may require

1. topical azole (Clotrimazole-Lotrimin) or allylamine (Terbinafine, Butenafine) or Ciclopirox (shampoo) 2. at least 1 week after symptoms have cleared. 3. a systemic antifungal agent (e.g., griseofulvin).

Contraindications and high-risk patients Sulfonamides and trimethoprim 1. Hypersensitivity Reactions; are frequent with 2. Can cause Hematologic: blood dyscrasias including 3. Sulfonamides promote (blank) in newborns by displacing bilirubin from plasma proteins 4. Because older sulfas can form crystalline aggregates they are contraindicated in 4. trimethoprim should be avoided in pts with folate deficiency such 5. Trimethoprim suppresses renal excretion of potassium and can 6. SMZs can intensify the effects of

1. topical sulfas and include: Mild reactions—rash, drug fever, photosensitivity to Severe reaction- Stevens-Johnson syndrome; d/c use if a rash is observed 2. including hemolytic anemia in patients with G6PD deficiency, agranulocytosis, leukopenia, thrombocytopenia, & bone marrow suppression 3. kernicterus 4. patients with severe renal disease and req reduced dosage for pts with renal impairment 5. as ETOH abuse and in pregnant women 6. promote hyperkalemia; Risks are elevated in those with renal impairment, & those taking drugs that elevate K+, including ACEIs, ARBs, aldosterone antagonists 7. warfarin, phenytoin, and sulfonylureas

Contraindications and high-risk patients Carbapenems 1. Imipenem can reduce blood levels of 2. Dosage should be reduced in patients

1. valproate, an anti-seizures med; the combo should be avoided 2. with renal impairment

- Understand empiric treatment and when to use: 1. It is used when 2. is initiated based on two main things: 3. Can be used in severe illnesses when 4. What is the protocol for these pts 5. IV vs. PO? 6. Bactericidal vs. Bacteriostatic

1. when cultures are not available or results are not back yet 2a. NP's knowledge of the patient's history, typical pathogens, gram stain results, and 2b. local susceptibility reports on which abx work best in certain geographic locations. 3. Critically ill pts need immediate empiric antibiotics 4. after first set of cultures is obtained, do not wait for results.​ Give empiric (broad-spectrum) abx 5. IV-for Critical or severe infections PO for Mild/moderate or pts; Switch from IV to PO once the patient is stable 6. Bactericidal antibiotics directly kill bacteria preferred for immunocompromised patients such as those with diabetes, HIV, cancer or overwhelming infections

Treatment for Systemic Fungal Infections List the two main types

Amphotericin B - Broad-spectrum antifungal - Highly toxic medication - Black box warning: Use in life-threatening infections only - Administered IV only: refusion reactions are common - Premedicate: acetaminophen plus diphenhydramine Azoles ie, Ketoconazole - Broad-spectrum antifungals - Inhibit CYP450

Antibiotics that require NO renal dose adjustment

Azithromycin-macrolide Ceftriaxone-Ceph 3rd gen Clindamycin-Lincosamides Doxycyline-tetra Linezolid Moxifloxacin-fouro Nafcillin Rifampin

Treatment Overview - List drugs for systemic infections - List drugs for superficial (local infections)

Clotrimazole is not active against onychomycosis (nail fungus) Fluconazole [Diflucan] is active against all three

Patient-Centered Care Across the Life Span-Aminoglycosides Infants • Aminoglycosides are approved to treat bacterial infections in infants younger than Children/adolescents • Aminoglycosides are Pregnant women • There is evidence that use of aminoglycosides in pregnancy can Breastfeeding women • (blank) is probably safe to use during lactation Older adults • Caution must be used regarding decreased

Infants • 8 days. Dosing is based on weight and length of gestation. Children/adolescents • safe for use against bacterial infections in children and adolescents. Pregnant women • harm the fetus. Breastfeeding women • Gentamicin; although there is limited information Older adults • renal function in the older adult.

Another Urinary AntiSeptic: Methenamine

Mechanism of Action • Methenamine is a prodrug that, under acidic conditions (pH <5.5), breaks down into ammonia and formaldehyde • formaldehyde denatures bacterial proteins, causing cell death

Patient-Centered Care Across the Life Span-Drugs for UTI: Nitrofurantoin, Methenamine & Fluoroquinolones Infants • (blank & blank) are recommended to treat infants with UTI. Children/adolescents • Methenamine hippurate is approved for use in children between Pregnant women • UTIs in pregnancy must be treated as Breastfeeding women • Fluoroquinolones have been Older adults • Nitrofurantoin should be

Infants • Ampicillin and gentamycin; Nitrofurantoin is contraindicated in infants less than one month of age. Trimethoprim/sulfamethoxazole should also be avoided in the early stages of infancy. Children/adolescents • 6-12 years of age. Methanamine mandelate can be used in children < 6 years of age. Pregnant women • complicated infections. Nitrofurantoin is contraindicated in the third trimester of pregnancy. Fluoroquinolones should also be avoided in pregnancy. Breastfeeding women • detected in breast milk at low doses. Short-term use during breastfeeding is acceptable. For greatest safety, breastfeeding should be avoided between 4 and 6 hours after a dose. Older adults • avoided in older adults with decreased renal function.

Patient-Centered Care Across the Life Span-Penicillins Infants • Penicillins are used safely in infants with Children/adolescents • Penicillins are a common drug used to treat Pregnant women • Although there are no well-controlled studies in pregnant women Breastfeeding women • (blank) is safe for use in breastfeeding mothers. Older adults • Doses should be adjusted in older adults with

Infants • bacterial infections, including syphilis, meningitis, and group A streptococcus. Children/adolescents • bacterial infections in children. Pregnant women • evidence we do have suggests there is no second or third trimester fetal risk. Breastfeeding women • Amoxicillin; Data are lacking regarding transmission of some other penicillins from mother to infant through breast milk. Older adults • renal dysfunction.

Lifespan considerations for Sulfonamides and trimethoprim Infants • Use of sulfonamides in infants younger than 2 months Pregnant women • Systemic sulfonamides & trimethoprim may cause birth defects if taken during Breastfeeding women • Sulfonamides are secreted in breast milk. Women should be warned that Older adults • Older patients are more likely to

Infants • can cause kernicterus, a potentially fatal condition. Pregnant women • the first semester. If taken near term, the infant may develop kernicterus; trimethoprim may impact folate levels Breastfeeding women • breastfeeding an infant younger than 2 months can cause kernicterus Older adults • adverse effects, and when experienced, the effects are more likely to be severe. Life-threatening effects—including neutropenia, Stevens-Johnson syndrome, and toxic epidermal necrolysis—occur more frequently in older adults.

Patient-Centered Care Across the Life Span Cephalosporins, Carbapenems, and Others Infants • Third-generation cephalosporins are used to Children/adolescents • Cephalosporins are commonly used to treat Pregnant women • (blank) carries a black box warning Breastfeeding women • (blank) are generally not expected to cause adverse effects in breastfed infants. Older adults • Doses should be adjusted in older adults with

Infants • treat bacterial infections in neonates as well as infants. Children/adolescents • bacterial infections in children, including otitis media and gonococcal and pneumococcal infections. Pregnant women • Televancin (Glycopeptide); secondary to risk for adverse developmental outcomes. All cephalosporins appear safe for use in pregnancy. Breastfeeding women • Cephalosporins Older adults • decreased renal function.

Patient Education-in general 1. Finishing the Prescribed Course

It is imperative that antibiotics not be discontinued prematurely. Early discontinuation is a common cause of recurrent infection, and the organisms responsible for relapse are likely to be more drug resistant than those present when treatment began

What drugs are considered safe during pregnancy?

PCNs, cephalosporins & erythromycin

Which antibiotics require renal dose adjustments? Agents that must be reduced in renal impairment Penicillins Cephalosporins

Penicillins - Penicillin Reduce to 50% if GFR <30 ml/min - Amoxicillin GFR<10 ml/min - Augmentin Reduce if GFR<30 ml/min Cephalosporins - Cefazolin GFR <50 ml/min; Reduce to 50% if GFR<10 - Cefuroxime - Cephalexin

MOA for Sulfonamides/Trimethoprim

Sulfonamides suppress bacterial growth by inhibiting key precursors of folate; Remember* all organisms depend on folate for DNA, RNA, and protein synthesis • Selective toxicity: it doesn't harm humans b/c mammalian cells can take up folate from their diet whereas bacteria must synthesize it from precursors

Other ways to organize classes of Drugs What are Antimetabolites?

Sulfonamides, Trimethoprim & Nitrofurantoin

Know how to treat Different types of Vagina - candida (vaginal yeast infection).

Topical miconazole. Oral fluconazole

Other ways to organize classes of Drugs - Bactericidal antibiotics directly kill bacteria and include

aminoglycosides, beta-lactams, fluoroquinolones, metronidazole, most antimycobacterial agents, streptogramins, vancomycin.

What types of infections are usually viral and do not warrant antibacterial agents?

community-acquired, mostly viral, upper respiratory tract infections​; - these infections are usually viral patients are exposed to all the risks of abx but have no chance of receiving benefits

MOA for Tetracyclines

tetracyclines suppress bacterial growth by inhibiting protein synthesis by binding to the 30S ribosomal subunit and thereby interfering with the messenger RNA-ribosome complex.

Alternative drugs to patients with a history of penicillin allergy

• If the allergy is mild, a cephalosporin is often an appropriate alternative • For many infections, vancomycin, erythromycin, and clindamycin are effective and safe alternatives

MOA for PCNs

• disruption of the bacterial cell wall • they are bactericidal; bacteria must be actively growing for them to work

Nitrofurantoin Mechanism of Action

• is a broad-spectrum antibacterial drug • produces bacteriostatic effects at low concentrations and bactericidal effects at high concentrations • Nitrofurantoin injures bacteria by damaging DNA

Mechanism of Action for Aminoglycosides

• these drugs bind to the 30S ribosomal subunit, causing inhibition & termination of protein synthesis, & production of abnormal proteins which is why they are bactericidal & NOT bacteriostatic

Other ways to organize classes of Drugs What is Beta Lactams?

• they have a β-lactam ring in their structure, the penicillins are known as β-lactam antibiotic • The β-lactam family also includes the cephalosporins, carbapenems, and aztreonam • All of the β-lactam antibiotics share the same mechanism of action: disruption of the bacterial cell wall • they are bactericidal; bacteria must be actively growing for them to work

List the 10 classes of Antibiotics name examples HINT (acronym): Abx Can Terminate Protein Synthesis For Microbial Cells Like Germs

● Aminoglycosides-gentamicin, streptomycin ● Cephalosporins-Cephalexin (Keflex)​ ● Tetracyclines-tetra/doxyclycline ● Penicillins-PCN G/V, amoxicillin ● Sulfonamides-trimethoprim/sulfamethoxazole ● Fluoroquinolones-ciprofloxacin ● Macrolides-erythromycin, Azithromycin ● Carbapenems-imipenem, meropenem ● Lincosamides-Clindamycin ● Glycopeptides-Vancomycin