Aminoglycoside dosing: one, two or three times a day?

The safety and efficacy of conventional aminoglycoside dosing regimens have been proven in clinical trials. Higher doses at longer intervals may be more effective if they result in higher peak serum levels of the drug, but few trials of "once-a-day" dosing have shown improved clinical outcome. The clinical safety of allowing trough serum levels to fall below the minimum inhibitory concentration is not established. Literal "once-a-day" dosing will result in drug accumulation and toxicity in patients with reduced renal clearance, and in potential lack of efficacy and the emergence of antibiotic-resistant organisms in those with increased renal clearance. However, modified "once-a-day" dosing, with the interval determined by the individual's renal clearance rate (hence avoiding subtherapeutic trough levels), will avoid these problems.