Aminoglycoside uptake into bacteria requires an electron transport chain-driven proton motive force. This explains why aminoglycosides are ineffective against anaerobes and why they demonstrate concentration-dependent killing. Which clinical dosing strategy exploits concentration-dependent killing?

• A Giving small doses every 4 hours to maintain plasma concentrations just above the MIC continuously
• B Extended interval (once-daily) dosing, giving the full daily dose as a single injection to maximise peak/MIC ratio, while exploiting the prolonged post-antibiotic effect ✓
• C Continuous infusion to maintain steady-state concentrations above the MIC for >90% of the dosing interval
• D Pulse dosing every 72 hours, waiting for complete aminoglycoside clearance before each dose to prevent resistance

Explanation

Aminoglycosides exhibit concentration-dependent killing — the higher the peak concentration relative to MIC (Cmax/MIC ratio >8–10 predicts efficacy), the greater the bacterial kill rate. They also have a prolonged post-antibiotic effect (PAE) — bacterial growth remains suppressed for 1–3 hours after drug levels fall below MIC. Extended-interval (once-daily) dosing exploits both properties: a single high peak maximises the Cmax/MIC ratio, the PAE covers the trough period, and the trough near zero allows recovery of proximal tubular cells, reducing nephrotoxicity and cochleotoxicity compared to multiple daily doses. β-Lactam antibiotics, in contrast, are time-dependent and require continuous or frequent dosing.

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

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