A RANDOMIZED COMPARISON OF THE SAFETY AND EFFICACY OF ONCE-DAILY GENTAMICIN OR THRICE-DAILY GENTAMICIN IN COMBINATION WITH TICARCILLIN-CLAVULANATE

PURPOSE: The primary purpose of the clinical trial was to assess the s afety and efficacy of once-a-day compared with three-times-a-day genta micin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations. PATIENTS AND METHODS: A tota l of 249 hospitalized patients with suspected or proven serious infect ions were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC , or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dos age for patients with estimated creatinine clearance values of greater than or equal to 80 mL/min was 5.1 mg/kg. With lower creatinine clear ance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Ev aluability required documentation of achievement of protocol-defined p eak serum gentamicin levels. RESULTS: Of the total 175 evaluable patie nts, there were no significant differences found between treatment reg imens with respect to clinical or microbiologic efficacy. Bedside audi ometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinin e values from baseline values, no differences in renal toxicity betwee n the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of rena l function, preservation of renal function was better in the gentamici n once-a-day patients as opposed to the gentamicin three-times-a-day p atients, P <0.01. CONCLUSIONS: Gentamicin once a day plus TC, gentamic in three times a day plus TC, and TC alone had similar effects in seri ously ill hospitalized patients. The incidence of nephrotoxicity was s imilar in the three treatment groups. Using a nonvalidated post-hoc an alysis, renal function was better preserved in gentamicin once-a-day TC and TC-only patients as opposed to gentamicin three-times-a-day TC. (C) 1998 by Excerpta Medica, Inc.