Pharmacodynamic Characterization of Nephrotoxicity Associated with Once-Daily Aminoglycoside

Abstract

Study Objective. To characterize nephrotoxicity associated with an individualized serum concentration target-specific, once-daily aminoglycoside (ODA) program.

Design. Concurrent and retrospective study.

Setting. University-affiliated trauma hospital.

Patients. Two hundred patients treated with ODA and 100 treated with individualized traditional dosing (TDA).

Interventions. Empiric dosing for both groups was based on patient-specific pharmacokinetics and severity of infection. Regimens were modified according to predetermined target maximum and minimum serum concentrations for both groups.

Measurements and Main Results. Nephrotoxicity occurred in 7.5% patients treated with ODA and 14.7% receiving TDA (p=0.05). Minimum serum concentrations, length of aminoglycoside therapy, and cumulative area under the curve (AUC) were all dependently related to nephrotoxicity, and concomitant vancomycin and other nephrotoxic drugs were independently related to the disorder. The cumulative AUC was greatest in patients receiving TDA (p=0.03), and the modeled probability of becoming toxic at any given cumulative AUC was significantly greater with TDA than with ODA (p<0.01). Clinical and microbiologic outcomes were similar between groups. Maximum concentration:minimum inhibitory concentration ratios were higher (p<0.01) and number of days to organism eradication was shorter in the ODA group (p=0.04).

Conclusion. The trend was toward decreased nephrotoxicity in patients treated with ODA compared with TDA, and at any given cumulative AUC, the risk of toxicity was lower for ODA.