Chemotherapy — Antimicrobials

🟢 Lite — Quick Review (1h–1d)

Chemotherapy — Key Facts for NEET PG

β-Lactam Antibiotics:

• Penicillins: Bactericidal, inhibit cell wall synthesis, inhibit transpeptidase (PBPs)
• Amoxicillin: Sensitive organisms — H. pylori, S. pneumoniae, S. pyogenes, E. coli
• Cephalosporins: 1st gen (Cefazolin) → gram-positive; 3rd gen (Ceftriaxone) → broad gram-negative
• Carbapenems (Meropenem): Very broad spectrum, last-resort

Fluoroquinolones:

• Ciprofloxacin, Levofloxacin, Moxifloxacin
• Mechanism: Inhibit DNA gyrase + topoisomerase IV → bactericidal
• Coverage: Gram-negative (incl. Pseudomonas); Levofloxacin/Moxifloxacin also atypicals

Aminoglycosides:

• Gentamicin, Amikacin, Streptomycin
• Mechanism: Inhibit 30S ribosomal subunit → bactericidal
• Use: Aerobic gram-negative (Pseudomonas, Klebsiella), synergy with β-lactams
• Toxicity: Ototoxicity, nephrotoxicity (monitor levels)

High-yield point: Bactericidal vs Static distinction — FQs, Aminoglycosides, Metronidazole = bactericidal

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🟡 Standard — Regular Study (2d–2mo)

Chemotherapy — NEET PG Study Guide

Mechanisms of Antimicrobial Action:

Mechanism	Drug Class	Example
Inhibit cell wall synthesis	β-lactams, Glycopeptides	Amoxicillin, Vancomycin
Inhibit protein synthesis (30S)	Tetracyclines, Aminoglycosides	Doxycycline, Gentamicin
Inhibit protein synthesis (50S)	Macrolides, Chloramphenicol, Lincosamides	Azithromycin, Chloramphenicol
Inhibit DNA synthesis	Fluoroquinolones	Ciprofloxacin
Inhibit RNA synthesis	Rifampicin	Rifampicin
Inhibit folate synthesis	Sulfonamides, Trimethoprim	Cotrimoxazole
Inhibit cell membrane	Polymyxins, Daptomycin	Colistin

β-Lactam Antibiotics — Detailed:

Penicillins:

• Natural: Benzylpenicillin (Penicillin G)
• Aminopenicillins: Amoxicillin, Ampicillin (broad spectrum)
• Anti-staphylococcal: Methicillin, Oxacillin, Cloxacillin (β-lactamase resistant)
• Antipseudomonal: Piperacillin (with tazobactam = Tazo)

Cephalosporin Generations:

Generation	Drug	Coverage
1st	Cefazolin	Gram-positive cocci (MRSA coverage: NO)
2nd	Cefuroxime	Gram-positive + some gram-negative
3rd	Ceftriaxone, Cefotaxime	Broad gram-negative, meningeal penetration
4th	Cefepime	Pseudomonas + gram-positive
5th	Ceftolozane	Broad incl. MDR Pseudomonas

Macrolides:

• Azithromycin, Clarithromycin, Erythromycin
• Mechanism: Bind 50S ribosomal subunit → bacteriostatic
• Coverage: Atypicals (Mycoplasma, Chlamydia, Legionella), gram-positive
• Key: Azithromycin = single dose for Chlamydia (1g stat)

Vancomycin:

• Glycopeptide — cell wall synthesis inhibitor
• Coverage: Gram-positive ONLY (MRSA, MRSE, Enterococcus faecalis)
• Toxicity: Red man syndrome (histamine release), nephrotoxicity, ototoxicity
• Monitor: Trough levels

Tetracyclines & Doxycycline:

• 30S inhibitor — bacteriostatic
• Coverage: Atypicals, Rickettsia, Chlamydia, Mycoplasma, Lyme disease
• DOXYCYCLINE: First-line for Rickettsial fevers, Chlamydia, Mycoplasma, prophylaxis (travel, malaria)

Metronidazole:

• Prodrug: Reduced by anaerobic bacteria → cytotoxic metabolites
• Coverage: Anaerobes (Bacteroides, C. diff), protozoa (Giardia, Entamoeba, Trichomonas)
• Use: Anaerobic infections, bacterial vaginosis, C. diff colitis, H. pylori

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🔴 Extended — Deep Study (3mo+)

Chemotherapy — Comprehensive NEET PG Notes

Antimicrobial Resistance Mechanisms:

1. Enzymatic inactivation: β-lactamases (blunted by β-lactamase inhibitors: clavulanic acid, tazobactam)
2. Altered target: MRSA (altered PBP2a), VRSA (altered cell wall precursor)
3. Decreased permeability: Gram-negative outer membrane barrier
4. Efflux pumps: Tetracycline resistance (Tet efflux)
5. Bypass pathway: Trimethoprim resistance

β-Lactam + β-Lactamase Inhibitor Combos:

Combination	Use
Amoxicillin + Clavulanic acid	Respiratory, skin, UTI
Piperacillin + Tazobactam	Nosocomial,Pseudomonas, neutropenic fever
Ceftriaxone + Sulbactam	Resistant gram-negatives

Carbapenems:

• Meropenem, Imipenem, Ertapenem, Doripenem
• Imipenem: Dehydropeptidase I inhibitor (add Cilastatin to prevent renal toxicity)
• Ertapenem: Once daily, no Pseudomonas coverage
• “Carbapenem-sparing” when treating ESBL producers: Use cephamycins or β-lactam/β-lactamase inhibitor combos

Fluoroquinolone Details:

Drug	Gram-negative	Gram-positive	Atypicals	Pseudomonas
Ciprofloxacin	+++	+	++	+++
Levofloxacin	++	++	+++	++
Moxifloxacin	++	+++	+++	—

FQ Black Box Warning: Tendon rupture, QT prolongation, C. difficile, exacerbate myasthenia gravis

Aminoglycoside Practical Points:

• Once-daily dosing (post-antibiotic effect allows concentration-dependent killing)
• Monitoring: Peak + trough levels, renal function
• Synergy with β-lactams: Cell wall agents facilitate aminoglycoside entry

Polymyxins (Last-Resort):

• Colistin (Polymyxin E), Polymyxin B
• Mechanism: Binds LPS → disrupts gram-negative outer membrane
• Use: MDR Pseudomonas, Acinetobacter, CRE
• Toxicity: Nephrotoxicity, neurotoxicity

Sulfonamides & Trimethoprim:

• Cotrimoxazole (SMX + TMP): Synergistic blocking of folate pathway
• Coverage: PCP (first-line prophylaxis/treatment), Nocardia, Stenotrophomonas, Salmonella
• TMP alone: UTI, bacterial diarrhea

Rifampicin:

• RNA synthesis inhibitor — potent inducer of CYP450 (↓ levels of OCP, warfarin, many drugs)
• Use: TB (4-drug therapy), MRSA prophylaxis, H. influenzae, N. meningitidis prophylaxis
• Dis colors body fluids orange/red

Antifungal Basics:

Class	Drug	Use
Polyenes	Amphotericin B, Nystatin	Systemic mycoses, oral candidiasis
Azoles	Fluconazole (candidiasis), Voriconazole (aspergillosis)
Echinocandins	Caspofungin	Invasive aspergillosis, candidemia

Antiviral Key Points:

• HIV: NRTIs (Tenofovir, Emtricitabine) + NNRTIs (Efavirenz) + PIs (Ritonavir) — HAART
• Hepatitis B/C: Tenofovir, Sofosbuvir, Ledipasvir — Direct-acting antivirals (DAAs)
• Herpes: Acyclovir (HSV, VZV) — guanine analog, needs viral thymidine kinase
• Influenza: Oseltamivir (neuraminidase inhibitor)

High-Yield Combinations:

• Synergy (1+1>2): β-lactam + aminoglycoside; SMX + TMP
• Antagonism: Bacteriostatic (Tetracycline) + Bactericidal (Penicillin)
• Broad gram-negative cover (PIPERACILLIN-TAZO + AMIKACIN): Nosocomial pneumonia, neutropenic fever

Clinical Scenarios Frequently Asked in NEET PG:

1. MRSA infection → Vancomycin OR Linezolid OR Daptomycin
2. ESBL-producing E. coli UTI → Carbapenem OR Nitrofurantoin
3. Pseudomonas aeruginosa pneumonia → Piperacillin-tazobactam OR Cefepime OR Meropenem
4. C. difficile colitis → Oral Vancomycin OR Fidaxomicin (NOT systemic metronidazole)
5. Meningitis (empiric) → Ceftriaxone + Vancomycin + Dexamethasone
6. TB first-line (4-drug): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol

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