Extended-interval aminoglycoside dosing (once-daily) is pharmacokinetically superior to thrice-daily dosing for bactericidal activity. Which PK/PD index justifies this approach?
- A Aminoglycosides exhibit concentration-dependent killing; the AUC/MIC and Cmax/MIC ratios predict efficacy, and single large doses achieve higher peak concentrations maximizing these ratios ✓
- B Time-dependent killing of aminoglycosides favors prolonged low-concentration exposure above MIC
- C Extended interval reduces the post-antibiotic effect, allowing bacteria to recover between doses
- D Once-daily dosing maintains trough concentrations above MIC for 24 hours more reliably
Explanation
Aminoglycosides are paradigmatic concentration-dependent antibiotics. Their killing is maximized by achieving high peak concentrations (Cmax), and the PK/PD indices that best predict outcome are Cmax/MIC (target ratio ≥8-10:1) and AUC24/MIC. Additionally, aminoglycosides demonstrate a prolonged post-antibiotic effect (PAE) — bacterial growth inhibition persists even when drug concentrations fall below the MIC. Once-daily dosing achieves higher Cmax, maximizes concentration-dependent killing, and exploits the PAE. Furthermore, nephrotoxicity and cochleotoxicity correlate with prolonged high trough levels, which are lower with extended-interval dosing.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.