Aminoglycosides are concentration-dependent antibiotics with a prolonged post-antibiotic effect (PAE). Which dosing strategy exploits this pharmacodynamic property to maximise efficacy while minimising nephrotoxicity?
- A Continuous IV infusion maintaining drug levels above MIC throughout the dosing interval
- B Once-daily extended-interval dosing to achieve a high Cmax/MIC ratio with drug-free intervals allowing renal tubular recovery ✓
- C Three-times-daily dosing to maintain time above MIC >40% of the dosing interval
- D Twice-daily dosing targeting an AUC/MIC ratio of >125 for gram-negative bacteria
Explanation
Aminoglycosides exhibit concentration-dependent killing: efficacy correlates with the Cmax/MIC ratio. Their prolonged post-antibiotic effect (PAE, 2–7 hours against gram-negatives) means bacterial killing continues even after concentrations fall below MIC. Once-daily extended-interval dosing achieves a high Cmax (maximising killing and PAE) and also provides drug-free troughs, which allows megalin/cubilin-mediated renal cortical drug saturation to recover — reducing proximal tubular accumulation and nephrotoxicity. Time-dependent killing (time above MIC) describes beta-lactams; AUC/MIC > 125 is the target for fluoroquinolones.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.