Bit · Pharm/Tox
Antibiotic Mechanism Classes
Every antibiotic on Step 1 attacks one of five bacterial targets. Group them by target and the side effects fall out of the chemistry.
Mechanism
Five targets, five mechanism categories:
- Cell wall synthesis — β-lactams (penicillins, cephalosporins, carbapenems, monobactams), vancomycin. Bactericidal. Most bacteria die because they can't make peptidoglycan.
- Protein synthesis (30S) — aminoglycosides (bactericidal), tetracyclines (bacteriostatic).
- Protein synthesis (50S) — macrolides, clindamycin, chloramphenicol, linezolid (all bacteriostatic except linezolid in some contexts).
- DNA / RNA synthesis — fluoroquinolones (DNA gyrase, topo IV), metronidazole (free radicals damaging DNA), rifampin (RNA polymerase).
- Folate synthesis — sulfonamides (PABA → DHF), trimethoprim (DHF → THF). Synergistic.
Differentiator Table
| Target | Class | Examples | Coverage | Signature toxicities |
|---|---|---|---|---|
| Cell wall — PBPs | Penicillins, cephalosporins, carbapenems, monobactams | Penicillin G, ampicillin, ceftriaxone, meropenem, aztreonam | Wide range; depends on generation | Hypersensitivity (anaphylaxis), C. diff, seizures (high-dose carbapenems) |
| Cell wall — D-Ala D-Ala | Glycopeptides | Vancomycin | Gram-positive (incl. MRSA, C. diff oral) | Nephrotoxicity, ototoxicity, red man syndrome (infusion rate) |
| 30S ribosome | Aminoglycosides | Gentamicin, tobramycin, amikacin | Gram-negative aerobes; synergy w/ β-lactam | NEPHROTOXICITY + OTOTOXICITY + neuromuscular blockade |
| 30S ribosome | Tetracyclines | Doxycycline, minocycline, tetracycline | Atypicals, Rickettsia, Lyme | Tooth discoloration, photosensitivity, GI; AVOID in pregnancy and <8 yrs |
| 50S ribosome | Macrolides | Azithromycin, erythromycin, clarithromycin | Atypical pneumonia, URI | QT prolongation, GI motility (erythromycin), CYP3A4 inhibitors |
| 50S ribosome | Lincosamides | Clindamycin | Anaerobes above diaphragm; gram-positives | C. DIFFICILE colitis |
| 50S ribosome | Oxazolidinones | Linezolid | Gram-positive incl. VRE, MRSA | Thrombocytopenia, serotonin syndrome (MAOI activity), peripheral neuropathy |
| DNA gyrase / topo IV | Fluoroquinolones | Ciprofloxacin, levofloxacin, moxifloxacin | Gram-negative, atypical pneumonia, UTI | Tendinopathy / rupture, QT prolongation, AVOID in pregnancy + <18 yrs, aortic aneurysm |
| DNA | Nitroimidazoles | Metronidazole | Anaerobes below diaphragm, protozoa | Disulfiram reaction with alcohol, metallic taste, neuropathy |
| RNA polymerase | Rifamycins | Rifampin | TB, prophylaxis | Orange body fluids, hepatotoxicity, CYP450 INDUCER |
| Folate | Sulfonamides | TMP-SMX | UTI, PCP | SJS, hemolysis in G6PD, hyperkalemia (TMP), AVOID in late pregnancy |
The Pivot
The way to learn this is by target → class → drugs → toxicities. NBME loves the toxicity questions: nephro + oto = aminoglycosides; tendon rupture = fluoroquinolones; C. diff = clindamycin (and broad-spectrum); orange fluids = rifampin; red man = vancomycin rate; SJS = sulfa.
NBME-Style Stem
A 24-year-old woman is treated with a 7-day course of an antibiotic for acute pyelonephritis. Two days after completion, she develops bilateral Achilles tendon pain and is unable to bear weight. Which class of antibiotic is most likely responsible?
Concept Anchor
Five bacterial targets, five mechanism classes — and once you know the target, the side effects fall out of where the drug binds. The toxicity is the fingerprint.