Pharmacology · USMLE Step 1

USMLE Antibiotics

Antibiotic classes, mechanism, spectrum of coverage, and one signature side effect per class.

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What is the mechanism of action of penicillins?
Inhibit bacterial cell wall synthesis by binding penicillin-binding proteins and cross-linking peptidoglycan
Penicillin G gram-positive and gram-negative coverage
Gram-positive cocci and rods; narrow gram-negative coverage (mainly Neisseria)
Most common allergic reaction to penicillins
IgE-mediated hypersensitivity (anaphylaxis, rash, urticaria)
Ampicillin gram-negative spectrum compared to penicillin G
Better gram-negative coverage (includes E. coli, Proteus, Haemophilus), but still susceptible to beta-lactamase
What does clavulanic acid do when combined with amoxicillin?
Irreversibly inhibits beta-lactamase, protecting amoxicillin from degradation
Cephalosporin mechanism of action
Inhibit bacterial cell wall synthesis like penicillins; beta-lactam ring binds penicillin-binding proteins
First-generation cephalosporin spectrum (e.g., cephalexin)
Good gram-positive (including Staphylococcus aureus), limited gram-negative, no anaerobes
Third-generation cephalosporin spectrum (e.g., ceftriaxone)
Improved gram-negative (including Enterobacteriaceae, Neisseria, Haemophilus), reduced gram-positive vs first-gen
Cephalosporin cross-reactivity with penicillin allergy
Low cross-reactivity (~1-2%) with modern cephalosporins; safe in most penicillin-allergic patients
Carbapenem spectrum (e.g., meropenem, ertapenem)
Broad spectrum: gram-positive, gram-negative, anaerobes; resistant to most beta-lactamases
Aminoglycoside mechanism of action
Inhibit bacterial protein synthesis by binding to 30S ribosomal subunit and causing misreading of mRNA
Aminoglycoside spectrum coverage
Gram-negative aerobes (e.g., Pseudomonas, E. coli, Klebsiella); poor activity against anaerobes and against gram-positive organisms when used alone (though useful in synergistic combination with cell wall-active agents against some gram-positive organisms like Enterococcus or Staphylococcus).
Dose-dependent nephrotoxicity caused by which antibiotic?
Aminoglycosides; risk increases with prolonged use, baseline renal impairment, and concurrent nephrotoxic drugs
Aminoglycoside-induced ototoxicity affects which cranial nerve?
Cranial nerve VIII (vestibulocochlear); causes irreversible hearing loss and vestibular dysfunction
Tetracycline mechanism of action
Inhibit bacterial protein synthesis by binding to 30S ribosomal subunit and blocking aminoacyl-tRNA entry

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