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Fluoroquinolones: Drugs
Ciprofloxacin, ofloxacin; respiratory fluoroquinolones: levofloxacin, moxifloxacin.
Fluoroquinolones: Mechanism
Inhibit prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV. Bactericidal. Oral absorption is markedly decreased by concurrent ingestion of divalent cations (e.g., dairy, antacids).
Fluoroquinolones: Clinical Use
Effective against gram ⊝ rods of urinary and GI tracts (including Pseudomonas), some gram ⊕ organisms, otitis externa, and community-acquired pneumonia.
Fluoroquinolones: Adverse Effects
- GI upset, superinfections, skin rashes, headache, dizziness.
- Less commonly: leg cramps, myalgias.
- Tendonitis or tendon rupture (especially in patients > 60 years old or on prednisone).
- Contraindicated in pregnancy, breastfeeding, and in children < 18 years old due to possible cartilage damage.
- May prolong QT interval.
Mnemonic: ‘Fluoroquinolones hurt attachments to your bones.’
Fluoroquinolones: Mechanism of Resistance
- Chromosome-encoded mutation in DNA gyrase.
- Plasmid-mediated resistance.
- Efflux pumps.
Daptomycin: Mechanism
Lipopeptide that disrupts gram ⊕ bacterial cell membranes by creating transmembrane channels.
Daptomycin: Clinical Use
Effective against S aureus skin infections (especially MRSA), bacteremia, infective endocarditis, and VRE.
Daptomycin: Adverse Effects
- Myopathy.
- Rhabdomyolysis.
Note: Not used for pneumonia (inactivated by surfactant). Mnemonic: ‘Dapto-myo-skin’—used for skin infections but can cause myopathy.
Metronidazole: Mechanism
Forms toxic free radical metabolites in bacterial cells, damaging DNA. Bactericidal and antiprotozoal.
Metronidazole: Clinical Use
Treats:
- Giardia.
- Entamoeba.
- Trichomonas.
- Gardnerella vaginalis.
- Anaerobes (Bacteroides, C difficile).
- Can replace amoxicillin in H pylori ‘triple therapy’ for penicillin-allergic patients.
Mnemonic: ‘GET GAP on the Metro’—treats anaerobic infections below the diaphragm (vs clindamycin for above diaphragm).
Metronidazole: Adverse Effects
- Disulfiram-like reaction with alcohol (flushing, tachycardia, hypotension).
- Headache.
- Metallic taste.
- Can cause tendonitis or tendon rupture in patients > 60 years old or on prednisone.
Note: Ciprofloxacin inhibits cytochrome P-450.
Linezolid: Mechanism
Inhibits protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit, preventing the formation of the initiation complex.
Linezolid: Clinical Use
Effective against gram ⊕ species, including MRSA and VRE.
Linezolid: Adverse Effects
- Myelosuppression (especially thrombocytopenia).
- Peripheral neuropathy.
- Serotonin syndrome (due to partial MAO inhibition).
Linezolid: Mechanism of Resistance
Point mutation of ribosomal RNA.
Macrolides: Drugs
Azithromycin, clarithromycin, erythromycin.
Macrolides: Mechanism
Inhibit protein synthesis by blocking translocation (‘macroslides’); bind to the 50S ribosomal subunit. Bacteriostatic.
Macrolides: Clinical Use
Used for atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram ⊕ cocci (streptococcal infections in penicillin-allergic patients), and B pertussis.
Macrolides: Adverse Effects
MACRO:
- Gastrointestinal Motility issues.
- Arrhythmia due to prolonged QT interval.
- Acute cholestatic hepatitis.
- Rash.
- Eosinophilia.
- Increases serum levels of theophylline and oral anticoagulants. Clarithromycin and erythromycin inhibit cytochrome P-450.
Macrolides: Mechanism of Resistance
Methylation of the 23S rRNA-binding site prevents drug binding.
Polymyxins: Drugs
Colistin (polymyxin E), polymyxin B.
Polymyxins: Mechanism
Cationic polypeptides that bind to phospholipids on the cell membrane of gram ⊝ bacteria, disrupting cell membrane integrity, causing leakage of cellular components, and cell death.
Polymyxins: Clinical Use
Used as salvage therapy for multidrug-resistant gram ⊝ bacteria (e.g., P aeruginosa, E coli, K pneumoniae). Polymyxin B is a component of triple antibiotic ointments for superficial skin infections.
