Antimicrobial Agents: Quinolones, Aminoglycosides, and Tetracyclines covers quinolones, aminoglycosides, and tetracyclines for INI CET (AIIMS PG).
Fluoroquinolones:
- Mechanism: Inhibit bacterial DNA gyrase (topoisomerase II) and topoisomerase IV — essential for DNA supercoiling and replication
- Bactericidal
- Examples: Ciprofloxacin (highest Pseudomonas activity), Levofloxacin (L-isomer), Moxifloxacin (broadest — anaerobic coverage), Ofloxacin, Norfloxacin (UTI only — poor systemic absorption)
Spectrum:
- Gram-negatives: E. coli, Klebsiella, Salmonella, Shigella, Neisseria, Pseudomonas
- Gram-positives: Some coverage (S. pneumoniae — levofloxacin, moxifloxacin; atypicals — Mycoplasma, Chlamydia, Legionella)
- Atypical mycobacteria (ciprofloxacin)
Adverse Effects (all fluoroquinolones — BLACK BOX WARNINGS):
- Tendon rupture (Achilles tendon — especially >60 years, corticosteroids): Fluoroquinolone-associated tendinopathy
- QT prolongation (moxifloxacin > levofloxacin > ciprofloxacin)
- CNS effects: Convulsions, confusion (especially in elderly)
- Photosensitivity
- Cartilage damage: Avoid in children <18 years (arthropathy in immature animals)
- C. difficile colitis (broad spectrum)
- Glycemic disturbances ( hypoglycemia in diabetics)
Aminoglycosides:
- Mechanism: Bind to 30S ribosomal subunit → misreading of mRNA → bactericidal
- Examples: Gentamicin, Tobramycin (Pseudomonas), Amikacin (most resistant), Streptomycin (TB), Neomycin (topical)
- Spectrum: Primarily gram-negative aerobes (E. coli, Klebsiella, Pseudomonas, Acinetobacter); also used synergistically with β-lactams for gram-positive infections (enterococcal endocarditis)
- PK/PD: Concentrations-dependent killing (high peak/MIC ratio); post-antibiotic effect
- Monitoring: Trough levels (toxicity); Peak levels (efficacy) — especially in patients with altered renal function
Adverse Effects (Aminoglycosides):
- Nephrotoxicity (most common — accumulates in renal cortex; tubular necrosis)
- Ototoxicity (vestibular and cochlear — cochlear: high-frequency hearing loss first; vestibular: vertigo, ataxia)
- Neuromuscular blockade (rare — avoid with myasthenia gravis; synergism with muscle relaxants)
⚡ Exam Tip for INI CET (AIIMS PG): In endocarditis due to enterococci, the combination of Penicillin G + Gentamicin is synergistic — gentamicin provides rapid bacterial killing while penicillin provides sustained inhibition. Gentamicin alone is NOT effective against enterococci.
Tetracyclines:
- Mechanism: Bind to 30S subunit (blocking A site) → prevent tRNA attachment → bacteriostatic
- Examples: Tetracycline, Doxycycline, Minocycline, Demeclocycline
- Spectrum: Broad — Rickettsia ( Rocky Mountain spotted fever), Chlamydia, Mycoplasma, Borrelia (Lyme disease), atypical pneumonia, cholera, acne (Propionibacterium)
- Doxycycline: Most commonly used tetracycline; good oral absorption; less fatty accumulation than tetracycline; used for STD prophylaxis (ceftriaxone + doxycycline for gonorrhea + chlamydia)
Adverse Effects (Tetracyclines):
- GI upset (esophagitis — take with plenty of water; avoid lying down)
- Photosensitivity (especially doxycycline)
- Tooth discoloration and enamel hypoplasia (deposits in developing teeth and bones) — AVOID in children <8 years and pregnancy
- Pseudotumor cerebri (benign intracranial hypertension)
- Fanconi-like syndrome (expired tetracyclines — renal tubular acidosis)
- Hepatotoxicity (especially in pregnancy)
Other Related Drugs:
- Glycylcyclines: Tigecycline — broader tetracycline (，克服 tetracycline resistance); used for complicated skin/soft tissue and intra-abdominal infections when other options unavailable; GI side effects prominent
- Oxazolidinones: Linezolid — binds to 23S rRNA of 50S (not the A site); bacteriostatic for most gram-positives; active against MRSA, VRE, penicillin-resistant pneumococci; SAE: Thrombocytopenia with prolonged use; MAO inhibition (serotonin syndrome with SSRIs — CONTRAINDICATED)