Antimicrobial & Chemotherapy

🟢 Lite — Quick Review (1h–1d)

Rapid summary for last-minute revision before your exam.

Antimicrobial chemotherapy is the selective use of chemical agents to kill or inhibit infecting microbes (bacteria, mycobacteria, fungi, viruses, protozoa) while sparing the host — the principle of selective toxicity. Agents are classified by spectrum (narrow vs broad), activity (bacteriostatic vs bactericidal), and PK/PD drivers (time-dependent vs concentration-dependent killing).

Five mechanisms: cell-wall inhibition, protein synthesis (50S/30S), nucleic acid synthesis, antimetabolite action, membrane disruption.
Bactericidal drugs are mandatory in endocarditis, meningitis, and neutropenic sepsis.
PD targets: β-lactams need T>MIC ≥ 40–50%; aminoglycosides need Peak/MIC ≥ 8–10 and AUC/MIC ≥ 400; fluoroquinolones need AUC/MIC ≥ 25.

Category	Best PK/PD index	Dosing implication
β-lactams, vancomycin	T > MIC	Frequent dosing or continuous infusion
Aminoglycosides, fluoroquinolones, daptomycin	Peak/MIC, AUC/MIC	Once-daily high dose

🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Mechanism-based Classification

Every NEET PG question on this topic hinges on matching the drug to one of five molecular targets. Inhibitors of cell-wall synthesis (β-lactams, glycopeptides, fosfomycin, D-cycloserine) bind PBPs or block peptidoglycan cross-linking. Protein synthesis inhibitors bind either the 50S subunit (macrolides, clindamycin, chloramphenicol, linezolid) or the 30S subunit (aminoglycosides, tetracyclines). Nucleic acid inhibitors include fluoroquinolones (DNA-gyrase/topoisomerase IV) and rifampicin (bacterial RNA polymerase). Antimetabolites (sulfonamides, trimethoprim, dapsone, flucytosine) block folic acid pathways. Membrane disruptors (polymyxins, daptomycin, amphotericin B, azoles) breach or bind ergosterol.

Pharmacokinetic–Pharmacodynamic Categories

PK/PD class	Driver	Optimising index	Drugs
Concentration-dependent + PAE	Cmax, AUC	Peak/MIC ≥ 8–10; AUC/MIC ≥ 400 (AG) or ≥ 25 (FQ)	Aminoglycosides, fluoroquinolones, daptomycin
Time-dependent, minimal PAE	Duration above MIC	T > MIC ≥ 40–50%	β-lactams, vancomycin
Time-dependent, long PAE	AUC	AUC/MIC	Tetracyclines, macrolides, clindamycin

Loading dose = (Cₚ desired × Vd) × F, used for aminoglycosides and vancomycin to reach therapeutic levels fast.
Renal adjustment uses Cockcroft-Gault: CrCl = [(140 − age) × wt × 0.85 if female] ÷ (72 × SCr).
Resistance arises via β-lactamases, AMEs, PBP2′ in MRSA, 23S rRNA methylation, porin loss, efflux pumps (Tet), or target bypass.

Indications for Combination Therapy

Synergism — β-lactam + aminoglycoside in enterococcal endocarditis; TMP-SMX in Pneumocystis.
Spectrum broadening — empiric therapy in sepsis before cultures.
Resistance prevention — TB (HRZE), HIV (HAART), malaria (ACT).

🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

Worked Numeric — Renal-adjusted Aminoglycoside Dosing

A 65-year-old male, 70 kg, SCr 2.0 mg/dL, needs gentamicin for Pseudomonas pneumonia. Estimate CrCl: CrCl = [(140 − 65) × 70] ÷ (72 × 2.0) = 36.4 mL/min — so the dosing interval extends from 8 h to 24 h, or the dose is reduced by the same factor. A target Peak/MIC of 8–10 for an MIC of 2 mg/L requires Cmax 16–20 mg/L — achievable with a 7 mg/kg loading dose and once-daily extended-interval administration.

Edge Cases & Traps

Vancomycin is time-dependent, not concentration-dependent; trough monitoring (15–20 mg/L for MRSA pneumonia) is the surrogate for T>MIC.
Macrolides are bacteriostatic, but azithromycin concentrates inside macrophages, making it effective against intracellular Legionella and Chlamydia.
Bacteriostatic vs bactericidal matters clinically in endocarditis, meningitis, and neutropenic sepsis — use bactericidal agents there.
De-escalation from broad-spectrum empiric therapy to the narrowest agent guided by culture data reduces C. difficile and resistance.
β-lactamase inhibitors (clavulanate, sulbactam, tazobactam) lack intrinsic activity but protect the partner β-lactam — recall they themselves have no useful MIC.

Common Exam Mistakes

Mistake	Correction
Treating vancomycin as concentration-dependent	It is time-dependent (T>MIC)
Using broad-spectrum empirically forever	De-escalate to narrowest agent with sensitivity
Ignoring renal adjustment for AGs/vancomycin	Always Cockcroft-Gault before dosing
Calling daptomycin safe for pneumonia	It is inactivated by pulmonary surfactant

Practice prompts:

A neutropenic patient on imipenem develops ESBL Klebsiella — what is the drug of choice and why?
Calculate T>MIC percentage for ceftriaxone 1 g IV q12h when MIC = 4 mg/L and free drug stays above MIC for 8 h.

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Antimicrobial & Chemotherapy