Aminoglycosides require energy-dependent transport into bacterial cells. Which statement about their concentration-dependent bactericidal activity and clinical application is most accurate?

• A They are best dosed as multiple small daily doses to maintain bacteriostatic concentrations above the MIC
• B Continuous infusion is preferred for aminoglycosides to provide sustained supra-MIC concentrations
• C Aminoglycosides exhibit a post-antibiotic effect (PAE) only at sub-MIC concentrations
• D Once-daily dosing achieves a high Cmax/MIC ratio, maximising bacterial killing while allowing a low-trough window to reduce nephrotoxicity ✓

Explanation

Aminoglycosides are concentration-dependent killers with a significant post-antibiotic effect (PAE). Once-daily dosing (extended-interval dosing) achieves high Cmax/MIC ratios that maximise bactericidal activity and also produces a 'trough window' during which drug levels are very low; this low-trough period allows renal proximal tubular cells to partially recover from aminoglycoside accumulation, reducing nephrotoxicity compared with multiple-daily dosing. The PAE ensures continued bacteriostasis even after drug levels fall below MIC.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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