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Antimicrobial Therapeutics Flashcards

Overview and exam-context reminders

  • NCCPA guidance on drug names: generic names are always provided on exams; trade/brand names are listed in parentheses only if deemed necessary by the NCCPA.
  • This content is a subset of the pharmacotherapeutics blueprint focused on antimicrobials, including indications, mechanisms of action (MOA), and mechanisms of resistance (MOR).
  • When testing scenarios present antibiotics, focus on:
    • Site of infection and whether the site is sterile (e.g., deep lung, CSF) or not (e.g., skin, urine).
    • Likely organisms at that site (gram-positive vs gram-negative).
    • Patient tolerances and allergies; local resistance patterns via antibiograms.
  • Antibiotic classification in this material splits into two broad groups:
    • Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams)
    • Non-beta-lactams (all other agents).
  • “ADX” in the lecture references antibiotics in general.
  • Important testing strategy terms:
    • Antibiogram: local susceptibility patterns
    • Incidence vs prevalence with C. difficile across antibiotics (highest incidence with clindamycin; highest prevalence with high-volume agents like oral aminopenicillins, oral cephalosporins, and oral fluoroquinolones).
  • Pregnant patients and antibiotics:
    • Use the pregnancy-letter safety categories (FAST mnemonic provided later).
    • Example: aminoglycosides and tetracyclines are generally avoided in pregnancy; doxycycline has caveats in kids and pregnancy.
  • Common exam pitfalls and tricks:
    • Epstein-Barr virus + aminopenicillin rash is a classic exam theme.
    • Doxycycline is the drug of choice for tick-borne infections (Rickettsia, Ehrlichia, Borrelia burgdorferi).
    • Do not rely on amantadine/rimantadine for influenza due to resistance.
    • Vancomycin trough goals and infusion-rate management to minimize red man syndrome.

Mechanisms and classification: beta-lactams vs non-beta-lactams

  • Beta-lactams: contain a beta-lactam ring; MOA = arrest cell wall synthesis by binding penicillin-binding proteins (PBPs).
    • MOR (common resistance): beta-lactamase production; alteration of PBPs.
    • Beta-lactamases cleave the beta-lactam ring, inactivating the drug.
  • Non-beta-lactams: various structures; broader variability in gram-positive/gram-negative coverage.
  • Common beta-lactams include penicillins, cephalosporins, carbapenems, and monobactams.
  • Key adverse-event themes across classes: QT prolongation (notably macrolides and fluoroquinolones), ototoxicity (aminoglycosides), nephrotoxicity (aminoglycosides and vancomycin in some contexts), and disulfiram-like reactions (metronidazole with alcohol).

Penicillins: classifications, MOA, MOR, and coverage

  • MOA (penicillins): arrest cell wall synthesis by binding PBPs; MOR primarily via beta-lactamase production and PBPs alterations.
  • Natural penicillins (e.g., penicillin G IV, penicillin VK oral; benzathine penicillin long-acting IM)
    • Good Streptococcus coverage; Strep pyogenes; syphilis treatment; limited gram-negative coverage.
  • Anti-staphylococcal penicillins (nafcillin IV; dicloxacillin oral)
    • Excellent Staph aureus coverage for MSSA; some Strep coverage; no MRSA coverage.
  • Aminopenicillins (ampicillin IV; amoxicillin oral)
    • Good Strep coverage including Streptococcus pneumoniae; Borrelia burgdorferi (Lyme); Listeria coverage; indications include respiratory infections, dental/oral infections, Lyme disease in kids <8 and in pregnancy; endocarditis prophylaxis in dental procedures.
  • Augmented aminopenicillins (ampicillin-sulbactam Unasyn IV; amoxicillin-clavulanate Augmentin oral)
    • Clavulanate/sulbactam inhibit beta-lactamase; extend activity to beta-lactamase–producing organisms; common uses include dental/oral infections, animal bites (pasteurella), URIs, COPD exacerbations, skin/soft tissue infections; no MRSA coverage.
  • Augmented extended-spectrum penicillins (piperacillin-tazobactam, Zosyn IV)
    • Very broad spectrum; covers both gram-positive and gram-negative organisms; includes Pseudomonas coverage; used in severe hospital- acquired infections; no MRSA coverage.

Cephalosporins: generations, MOA, MOR, and coverage

  • Generations concept: as generations increase, gram-positive coverage tends to decrease while gram-negative coverage tends to increase.
  • First generation: strong gram-positive coverage; limited gram-negative coverage; MSSA and Strep coverage; examples: cefazolin (Ancef IV), cephalexin (Keflex oral).
    • Uses: skin/soft tissue infections; perioperative prophylaxis; uncomplicated cystitis; pregnancy considered generally safe.
  • Second generation: better coverage for respiratory pathogens; examples: cefuroxime (Ceftin oral, Zinacef IV).
  • Third generation (oral): cefdinir (Omnicef), cefpodoxime (Vantin)
  • Third generation (parenteral): ceftriaxone (Rocephin) – note biliary sludging/pseudochololithiasis risk; broad gram-negative coverage; crosses BBB; indications include meningitis, CAP, gonorrhea; also used for abdominal/pelvic infections; gonorrhea treatment role is with Rocephin in US practice.
  • Fourth generation: cefepime (Maxipime)
    • Primarily gram-negative with good Pseudomonas coverage; used in hospitalized/severe infections.
  • Fifth generation: ceftaroline (Teflaro)
    • Covers MRSA in addition to typical gram-positive/negative coverage; approved for community-acquired pneumonia and skin/soft tissue infections.
  • Beta-lactamase inhibitors combined with cephalosporins are not common in the standard cephalosporin classes (the main inhibitors are paired with penicillins in Augmentin-like products, not cephalosporins).

Beta-lactamase inhibitors and combination penicillins (augmentation strategy)

  • Purpose: inhibitors like clavulanic acid, sulbactam, and tazobactam block bacterial beta-lactamases, thereby preventing inactivation of the penicillin.
  • This extends penicillin activity against beta-lactamase–producing organisms and enables activity against more resistant strains.

Non-beta-lactams: key agents and features

  • Vancomycin (glycopeptide)
    • MOA: inhibits cell wall synthesis; MOR: alterations in binding site.
    • Formulations: IV (systemic infections, MRSA), oral (local GI infections, e.g., C. difficile) with no systemic absorption.
    • Adverse effects: ototoxicity, nephrotoxicity; vancomycin infusion reaction (red man syndrome) mitigated by slower infusion (60 minutes) and trough monitoring.
    • Dosing/monitoring: trough levels (taken just before next dose) aimed at ext{trough} o 10-20 (mcg/mL). If >20, dose reduction considered.
  • Lipoglycopeptides (delbavancin, oritavancin)
    • Derivatives of vancomycin; long-acting, often single-dose or weekly dosing; approvals include SSTIs; favorable for outpatient use due to less IV-line maintenance; generally lower nephrotoxicity than vancomycin; may cause mild infusion reactions.
  • Vancomycin family notes
    • Oral vancomycin has no systemic absorption; IV vancomycin is used for systemic MRSA and other gram-positive infections; dalbavancin and oritavancin are outpatient-friendly due to long half-lives.

Tetracyclines

  • MOA: inhibit 30S ribosomal subunit; MOR: efflux pumps as a key resistance mechanism.
  • Agents: doxycycline (most commonly used), minocycline, tetracycline.
  • Important drug interactions and cautions:
    • Do not combine with isotretinoin (risk of pseudotumor cerebri).
    • Chelation with multivalent cations (e.g., calcium) reduces absorption; separate dosing by 2–4 hours when taking dairy or calcium supplements.
    • Photosensitivity; increased sun sensitivity.
    • Pregnancy category D; tooth and bone development risks; avoided in pregnancy and in children <8 years (though short courses in children may have less risk per some studies).
  • Indications and coverage:
    • Tick-borne diseases (Rickettsial infections: Rocky Mountain spotted fever, etc.; Ehrlichia; Borrelia burgdorferi)
    • MRSA coverage in some settings (variable by region)
    • Respiratory pathogens including Streptococcus pneumoniae; atypical pathogens (Chlamydia, Legionella, Mycoplasma)
    • Non-gonococcal urethritis and cervicitis; chlamydial infections in pregnancy; CAP; alternative for tick-borne illnesses; drug of choice for rickettsial infections.
  • Doxycycline-specific notes:
    • Most commonly used tetracycline; central role in tick-borne illness; also used for Lyme in kids and pregnancy (with caveats, see FAST antibiotics).

Macrolides

  • MOA: inhibit 50S ribosome.
  • MOR: ribosomal mutations and efflux; resistance patterns vary by organism.
  • Drugs: erythromycin, clarithromycin, azithromycin (oral; erythrocin also IV/other forms).
  • Adverse effects and cautions:
    • Erythromycin: GI motility effects; less favored as an antibiotic due to GI issues.
    • Azithromycin: QT prolongation risk; generally well tolerated; minimal CYP interactions but still watch QT risk.
    • Clarithromycin: potent CYP3A4 inhibitor; significant drug interaction potential (warfarin, statins, etc.); FDA warning about potential increased risk of cardiac events in patients with heart disease.
  • Indications:
    • Bordetella pertussis (whooping cough) – macrolide of choice.
    • Community-acquired pneumonia (CAP) – resistance concerns; not always first-line due to resistance, but still used.
    • Pharyngitis, otitis media, nongonococcal urethritis and cervicitis (especially azithromycin for chlamydia in pregnancy).
    • H. pylori treatment regimens (with other agents).
  • Fidaxomicin (Dificid) as a macrolide-class note:
    • Fidaxomicin is a macrolide-like agent, oral only, with a single indication for C. difficile infection; dosing: typically 200\,\text{mg} PO BID for 10\,\text{days}, recurrent disease may use the same dose or a pulse dosing regimen (two 200 mg BID for 10 days, then 200 mg BID every other day for 20 days).

Oxazolidinones

  • Drugs: linezolid (Zyvox), tedizolid (sivextro).
  • MOA: inhibit 50S ribosome; MOR: relatively rare; ribosomal mutations.
  • Spectrum: gram-positive organisms including MRSA and VRE.
  • Pharmacology: available IV and oral; generally well tolerated but watch for drug interactions.
  • Notable adverse effects:
    • Serotonin syndrome risk with concomitant SSRIs (due to MAOI-like effects).
    • Bone marrow suppression (usually reversible after drug cessation).
    • Hypertensive crisis (rare).
  • Indications: community-acquired pneumonia, hospital-acquired pneumonia, skin and soft tissue infections; MRSA and VRE coverage.

Lincosamides

  • Drug: clindamycin (IV or oral).
  • MOA: inhibits 50S ribosome; MOR: ribosomal target modification.
  • Coverage: good anaerobic coverage, particularly above the diaphragm; dental infections; lung abscesses; some skin/soft tissue infections.
  • MRSA coverage is variable and regional resistance can be high; watch for C. diff risk with clindamycin use.

Aminoglycosides

  • Drugs: gentamicin, tobramycin (IV); gentamicin also available as topical/ophthalmic; tobramycin also available IV and inhaled.
  • MOA: inhibit 30S ribosomal subunit; MOR: ribosomal modification and efflux mechanisms.
  • Spectrum: primarily gram-negative organisms; good Pseudomonas coverage; often used in hospital settings.
  • Toxicities: nephrotoxicity (often reversible with stopping), ototoxicity (can be permanent); trough monitoring essential to minimize toxicity.
  • Dosing considerations: consider trough levels just prior to next dose; careful dosing in hospital settings.
  • Special notes: inhaled tobramycin for cystic fibrosis infections; topical forms for local infections.

Fluoroquinolones

  • MOA: inhibit bacterial DNA topoisomerases (DNA gyrase and topoisomerase IV); MOR: mutations in these targets.
  • Key cautions:
    • Do not co-administer with QT-prolonging drugs; risk amplified.
    • Multivalent cations (e.g., magnesium) reduce absorption; many antacids contain magnesium, so separate dosing from fluoroquinolones.
  • Major adverse effects: arthropathy in children (<18 years) due to effects on developing cartilage; possible Achilles tendon rupture; CNS effects; photosensitivity; dysglycemia; QT prolongation.
  • Spectrum and agents:
    • Ciprofloxacin (Cipro): non-respiratory fluoroquinolone; good gram-negative coverage including Pseudomonas; available oral/IV; limited gram-positive coverage.
    • Levofloxacin (Levaquin) and Moxifloxacin (Avelox): respiratory fluoroquinolones with enhanced Streptococcus pneumoniae and atypical coverage; oral/IV available.
  • Indications:
    • Ciprofloxacin: complicated abdominal/pelvic infections, traveler's diarrhea, diverticulitis (often with metronidazole), complicated UTIs (pyelonephritis, prostatitis).
    • Levofloxacin/Moxifloxacin: CAP; abdominal-pelvic infections similar to ciprofloxacin; broad coverage including atypicals.
  • Important notes:
    • Fluoroquinolones are among the few oral agents with reliable Pseudomonas coverage (especially ciprofloxacin).

Trimethoprim-sulfamethoxazole (TMP-SMX)

  • MOA: inhibition of folate synthesis; MOR: altered dihydrofolate reductase and related pathways.
  • Interactions:
    • Inhibits CYP2C9; increases INR with warfarin; watch drug interactions and bleeding risk.
    • Potassium retention risk with concomitant ACE inhibitors/ARBs and spironolactone leading to hyperkalemia.
  • Adverse effects:
    • Hypersensitivity reactions; reversible myelosuppression with higher doses.
    • Hemolytic anemia in G6PD-deficient patients.
  • Indications:
    • Pneumocystis jirovecii pneumonia (PJP), broader gram-negative coverage including UTIs; MRSA coverage in some contexts.
  • Dosing notes: oral and IV formulations available.

Nitroimidazoles

  • Drugs: metronidazole (Flagyl), tinidazole (Tindamax).
  • MOA: DNA damage in anaerobic organisms; MOR: limited documented resistance.
  • Indications:
    • Anaerobic infections (below the diaphragm) and intra-abdominal infections; BV; trichomoniasis; Gardnerella vaginalis; C. difficile (historical first-line; now preferred regimens include fidaxomicin or oral vancomycin).
  • Adverse effects:
    • Metallic taste; disulfiram-like reaction with alcohol; teratogenic concerns in early pregnancy; caution with first-trimester use.
  • Dosing notes: metronidazole available oral/IV; tinidazole oral only.

Nitrofurantoin

  • MOA: mechanism not fully understood; primarily urinary tract activity.
  • Indication: urinary pathogens; concentrated in urine, not effective for pyelonephritis or prostatitis (stays in bladder).
  • Cautions: long-term use associated with pulmonary fibrosis.
  • Formulations: nitrofurantoin (Macrobid/Macrodantin) oral.

Anti-mycobacterial agents (anti-tuberculosis therapy)

  • Latent TB vs active TB:
    • Latent TB: typically a single-drug regimen; active TB requires multidrug therapy. Latent treatment examples include isoniazid (INH) for 9 months (historical standard) vs rifampin for 4 months (preferred now for latent TB).
  • Isoniazid (INH)
    • Latent TB: 9-month therapy; active TB component possible.
    • Adverse considerations: alcohol increases risk of transaminase elevations; peripheral neuropathy risk mitigated with pyridoxine (vitamin B6).
  • Rifampin (rifampin)
    • Preferred latent TB agent now; 4 months of therapy; urine discoloration and stains on clothing are common warnings.
    • Induces hepatic enzymes; contraindicated with certain HIV meds due to drug interactions (enzyme induction can inactivate some HIV therapies).
  • Pyrazinamide (PZA)
    • Component of active TB therapy; main risk: non-gouty polyarthralgia; NSAIDs used for relief.
  • Ethambutol (EMB)
    • Component of active TB therapy; main risk: color vision changes; color blindness testing recommended during treatment.

Antivirals: herpes, influenza, and older agents

  • Antiherpetic agents (for HSV and VZV):
    • Acyclovir (IV and oral and topical forms), Valacyclovir (oral), Famciclovir (oral).
    • Indications: HSV, VZV (shingles, chickenpox).
    • Tolerability: generally well tolerated; mild GI or headache; IV formulation for severe infections.
  • Anti-influenza agents:
    • Oseltamivir (Tamiflu) – oral; Zanamivir (Relenza) – inhaled; Baloxavir marboxil (Xofluza) – oral; all cover influenza A and B.
    • Pregnancy considerations: baloxavir cautioned; limited data; oseltamivir or zanamivir preferred in pregnancy.
    • Zanamivir cautions: inhaled formulation; can cause bronchospasm; avoid in asthma.
  • Older influenza agents (not effective now): Amantadine and Rimantadine; resistance has developed; not recommended as first-line choices.

Antifungals

  • Polyenes:
    • Amphotericin B: broad-spectrum, highly effective but with significant toxicity (nephrotoxicity and hepatotoxicity); not first-line; reserved for severe/refractory infections.
    • Nystatin: topical azole-adjacent agent; used for oral thrush (swish-and-swallow) and oropharyngeal candidiasis; minimal systemic toxicity.
  • Azoles (end in -azole): topical and systemic formulations
    • Systemic example: Fluconazole (Diflucan)
    • Common uses: candidal esophagitis, vulvovaginal candidiasis; oral or IV; inhibits CYP2C9; potential QT prolongation; careful with warfarin and other CYP2C9 substrates.
    • Interactions and cautions: CYP inhibition can increase levels of other drugs; monitor QT in susceptible patients.
  • Allylamines:
    • Terbinafine (Lamisil): topical and oral; used for onychomycosis and dermatophyte infections; potentially hepatotoxic; liver enzyme monitoring recommended.

Practical notes and exam-oriented pearls

  • MRSA coverage: oral agents (high-yield) – doxycycline and minocycline; TMP-SMX; linezolid and tedizolid also active but typically more expensive with higher adverse-effect burden; clindamycin may be used but resistance varies by locale.
  • Pseudomonas coverage:
    • Oral: ciprofloxacin and levofloxacin are the main options with Pseudomonas activity; moxifloxacin has poor urinary penetration and is less favored for UTIs.
    • IV/Parenteral broad-spectrum options include piperacillin-tazobactam, cefepime, carbapenems (with caveats), fluoroquinolones, and aminoglycosides.
  • MRSA-active beta-lactams:
    • Ceftaroline (5th gen cephalosporin) is the notable beta-lactam with MRSA coverage.
    • Daptomycin and tigecycline are other intravenous options for certain MRSA infections, but they were not the focus here.
  • Pseudomonal coverage specifics:
    • Piperacillin-tazobactam (Zosyn) offers robust Pseudomonas coverage; cefepime also covers Pseudomonas; aminoglycosides and certain fluoroquinolones provide additional access.
  • Dosing and monitoring highlights:
    • Vancomycin trough target typically ext{trough} o 10-20\text{ mcg/mL}; adjust dosing if troughs exceed 20; infusion over at least 60\text{ min} to reduce red man syndrome.
    • Metronidazole: avoid alcohol due to disulfiram-like reaction; avoid in first trimester where risk is discussed; monitor for GI symptoms.
    • Tetracyclines: avoid in pregnancy; separate calcium-containing products from dosing by 2-4\text{ hours}; watch for photosensitivity.
    • Fluoroquinolones: monitor for tendon risk, CNS effects; avoid in children; avoid coadministration with QT-prolonging drugs and with multivalent cations.
    • TMP-SMX: monitor INR if on warfarin; risk of hyperkalemia with other potassium-sparing meds; avoid in G6PD deficiency where hemolytic anemia risk higher.
    • Macrolides: azithromycin QT prolongation risk; clarithromycin interacts with CYP3A4 substrates; erythromycin GI effects.
    • Aminoglycosides: monitor troughs; watch renal function due to nephrotoxicity; risk of irreversible ototoxicity.
  • Pregnancy and safety (FAST antibiotic mnemonic):
    • F – Fluoroquinolones: potential joint/cartilage toxicity (arthropathy)
    • A – Aminoglycosides: cranial nerve VIII toxicity risk (fetal hearing loss)
    • S – Sulfonamides: kernicterus risk in neonates; avoid near term
    • T – Tetracyclines: tooth/bone development concerns
    • Use these associations as rough guides; consult current guidelines for specifics.
  • Penicillin allergy evaluation strategy (on exams):
    • Cross-reactivity with cephalosporins depends on the R1 side chain similarity; if the patient’s penicillin reaction involved a simple rash, cephalosporin with no shared R1 side chain may be considered; if a serious reaction (anaphylaxis, angioedema), avoid beta-lactams as a whole; skin testing alone does not predict anaphylaxis risk; always clarify the reaction details before choosing alternatives.
  • Epstein-Barr virus (EBV) and antibiotic rash:
    • In EBV infection, giving an aminopenicillin (e.g., ampicillin) commonly provokes a generalized maculopapular rash in >90% of cases; this is a classic exam pearl.
  • C. difficile considerations:
    • Highest incidence with clindamycin; highest prevalence with high-volume antibiotics (oral aminopenicillins, oral cephalosporins, and oral fluoroquinolones) due to widespread use.
    • First-line C. difficile therapy now tends to favor fidaxomicin or oral vancomycin over metronidazole as part of updated guidelines.

Quick-reference drug highlights (selected highlights for study nav)

  • MRSA coverage (oral): doxycycline, minocycline, TMP-SMX; +/- clindamycin depending on local resistance.
  • MRSA coverage (IV): vancomycin; linezolid; tedizolid; ceftaroline (5th-gen cephalosporin).
  • Pseudomonas coverage (oral): ciprofloxacin; levofloxacin.
  • Pseudomonas coverage (IV): piperacillin-tazobactam, cefepime, meropenem, doripenem, imipenem, aminoglycosides.
  • MRSA coverage with beta-lactams: ceftaroline.
  • C. difficile therapy: fidaxomicin or oral vancomycin preferred over metronidazole in many guidelines.
  • Tick-borne infections: doxycycline (drug of choice for many tick-borne pathogens).
  • TB regimens:
    • Latent TB: rifampin 4 months or isoniazid + pyridoxine (with monitoring) depending on guidelines.
    • Active TB: multidrug regimen including isoniazid, rifampin, pyrazinamide, ethambutol; monitor liver enzymes and vision testing for ethambutol.

Summary: key takeaways for exam prep

  • Know major MOAs and MORs for each class; especially beta-lactams (beta-lactamases and PBPs) and non-beta-lactams (ribosome or DNA-targeted mechanisms).
  • Memorize generation-based cephalosporin coverage trends and standout agents (ceftriaxone for meningitis, ceftriaxone + gonorrhea role, cefepime for Pseudomonas, ceftaroline for MRSA).
  • Remember safety profiles and pregnancy categories (FAST mnemonic) and specific cautions (e.g., tetracyclines in pregnancy/kids, fluoroquinolones in children, macrolide QT considerations).
  • Use antibiogram-based reasoning to tailor empiric therapy to local resistance patterns.
  • Distinguish correct use-cases for vancomycin oral vs IV, and recognize the role of newer lipoglycopeptides (dalbavancin, oritavancin) for outpatient therapy.
  • Be prepared to apply exam classics (EBV-rash with ampicillin, C. difficile therapy changes, pontential drug interactions with statins/warfarin, and antibiotic-associated adverse effects).

References and quick glossary

  • Antibiogram: local susceptibility patterns by organism
  • MOR: mechanism of resistance
  • MOA: mechanism of action
  • FAST antibiotics: F=Fluoroquinolones, A=Aminoglycosides, S=Sulfonamides, T=Tetracyclines
  • MRSA: methicillin-resistant Staphylococcus aureus
  • Pseudomonas: a common gram-negative pathogen often requiring broad coverage
  • C. difficile: Clostridioides difficile infection, often associated with broad-spectrum antibiotic use
  • R1 side chain: structural feature in penicillins/cephalosporins critical for cross-reactivity decisions

Final notes

  • Always cross-check against current guidelines and local resistance data when preparing for exams or clinical decisions.
  • The content above mirrors the lecture’s emphasis on categorization, MOA/MOR, organism coverage, safety, pregnancy considerations, and practical testing strategies.