Tobramycin exhibits concentration-dependent killing and a post-antibiotic effect (PAE). The clinical implication is that tobramycin is best dosed as:

• A Continuous infusion to maintain concentrations above the MIC for >90% of the dosing interval
• B Thrice daily equal doses to maintain steady-state concentrations
• C Twice daily dosing timed to coincide with peak bacterial growth phase
• D Once-daily high dose achieving high Cmax/MIC ratio (>8–10), exploiting PAE to reduce dosing frequency and nephrotoxicity ✓

Explanation

Aminoglycosides demonstrate concentration-dependent killing: the greater the Cmax/MIC ratio, the faster and more complete the bactericidal effect. The PAE (bacteria continue to be suppressed even after drug concentration falls below MIC) further extends the antimicrobial effect. Once-daily dosing achieves higher Cmax (better killing) while allowing trough levels to approach zero before the next dose, reducing the risk of accumulation-related nephrotoxicity and ototoxicity. This is the preferred strategy for aminoglycosides.

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

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