Gentamicin exhibits concentration-dependent killing and a significant post-antibiotic effect (PAE). These properties justify once-daily (extended interval) dosing over traditional three-times daily dosing. The key advantage of extended interval aminoglycoside dosing is:
- A Achieving high Cmax/MIC ratios (>10) to maximise bactericidal killing while permitting troughs near zero, reducing adaptive resistance and nephrotoxicity ✓
- B Achieving higher troughs to exceed MIC throughout the dosing interval
- C Prolonging the time above MIC which is the key PK/PD index for aminoglycosides
- D Allowing renal tubular cells to recover from aminoglycoside uptake during the low-trough period, with no effect on bactericidal activity
Explanation
Aminoglycosides display concentration-dependent killing: bactericidal activity maximally correlates with Cmax/MIC ratio (optimal target >10) and AUC/MIC. Once-daily dosing achieves a higher Cmax per dose, optimising the Cmax/MIC ratio for maximum killing. Additionally, allowing troughs near zero (below 1 mg/L) serves two purposes: it exploits the saturable uptake mechanism in renal proximal tubule cells (which accumulate aminoglycosides at steady-state in conventional dosing, causing nephrotoxicity), and it minimises 'adaptive resistance' — a phenomenon where bacteria upregulate efflux pumps with sustained exposure. The PAE means that bacterial killing continues even after concentrations fall below MIC, making prolonged low-level exposure unnecessary.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.