Antimicrobial Agents: Mechanisms, Classes & Resistance

Antibiotics succeed because of selective toxicity — they attack structures bacteria have and we don’t. The cleanest way to learn them is by where they strike the bacterial cell. Map the target, and the class, spectrum, and key toxicities fall into place.

1. Cell-wall synthesis inhibitors

• β-lactams (penicillins, cephalosporins, carbapenems, monobactams) bind penicillin-binding proteins, blocking peptidoglycan cross-linking — bactericidal. Resistance is mainly via β-lactamases.
• Glycopeptides (vancomycin) bind the D-Ala-D-Ala terminus — used for MRSA and C. difficile.

2. Cell-membrane agents

Polymyxins (colistin) disrupt the Gram-negative outer membrane — a last-resort drug, nephrotoxic. Daptomycin depolarises the Gram-positive membrane.

3 & 4. Protein-synthesis inhibitors

• 30S: aminoglycosides (gentamicin — bactericidal, nephro/ototoxic) and tetracyclines (bacteriostatic; avoid in children/pregnancy — teeth).
• 50S: macrolides (azithromycin), chloramphenicol (grey baby syndrome, aplastic anaemia), clindamycin (C. difficile colitis), linezolid.

Mnemonic — “buy AT 30, CCEL at 50“: Aminoglycosides & Tetracyclines at 30S; Chloramphenicol, Clindamycin, Erythromycin (macrolides), Linezolid at 50S.

5. Nucleic-acid inhibitors

• Fluoroquinolones (ciprofloxacin) inhibit DNA gyrase / topoisomerase IV — tendon rupture, QT prolongation.
• Rifampicin inhibits bacterial RNA polymerase — a potent enzyme inducer; colours secretions orange.

6. Folate / anti-metabolites

Sulfonamides block dihydropteroate synthase and trimethoprim blocks dihydrofolate reductase — together (co-trimoxazole) they give sequential blockade, synergistic and bactericidal.

Bactericidal vs bacteriostatic

Cidal (kill): β-lactams, vancomycin, aminoglycosides, fluoroquinolones, rifampicin, metronidazole. Static (inhibit): tetracyclines, macrolides, chloramphenicol, clindamycin, sulfonamides, trimethoprim, linezolid.

How resistance arises

• Enzymatic inactivation — β-lactamases, aminoglycoside-modifying enzymes.
• Target modification — altered PBPs (MRSA), ribosomal/DNA-gyrase mutations.
• Reduced uptake / efflux pumps, and bypass pathways.

Exam tip: anchor every antibiotic to its target site first (the diagram above). From the site you can reconstruct the class, whether it’s cidal or static, and its signature toxicity — exactly the structure examiners reward.

Selective toxicity is the thread running through the whole topic. Learn the six targets, hang each drug on its hook, and antimicrobial chemotherapy becomes one of the most logical chapters in pharmacology.