Pharmacodynamic characterization of nephrotoxicity associated with once-daily aminoglycoside

Study Objective. To characterize nephrotoxicity associated with an individu alized 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 indivi dualized traditional dosing (TDA). Interventions. Empiric dosing for both groups was based on patient-specific pharmacokinetics and severity of infection. Regimens were modified accordi ng to predetermined target maximum and minimum serum concentrations for bot h groups. Measurements and Main Results. Nephrotoxicity occurred in 7.5% patients tre ated with ODA and 14.7% receiving TDA (p=0.05). Minimum serum concentration s, length of aminoglycoside therapy, and cumulative area under the curve (A UC) were all dependently related to nephrotoxicity, and concomitant vancomy cin and other nephrotoxic drugs were independently related to the disorder. The cumulative AUC was greatest in patients receiving TDA (p=0.03), and th e modeled probability of becoming toxic at any given cumulative AUC was sig nificantly greater with TDA than with ODA (p<0.01). Clinical and microbiolo gic outcomes were similar between groups. Maximum concentration:minimum inh ibitory concentration ratios were higher (p<0.01) and number of days to org anism eradication was shorter in the ODA group (p=0.04). Conclusion. The trend was toward decreased nephrotoxicity in patients treat ed with ODA compared with TDA, and at any given cumulative AUG, the risk of toxicity was lower for ODA.