ASSESSMENT OF THE ENZYMURIA RESULTING FROM GENTAMICIN ALONE AND COMBINATIONS OF GENTAMICIN WITH VARIOUS BETA-LACTAM ANTIBIOTICS

OBJECTIVE: To determine the propensity of p-lactam antimicrobials to a meliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN : Two open, randomized, double-blind, parallel-group studies were cond ucted in young, healthy, male volunteer subjects. Using a common proto col, 24-hour urine collections were analyzed for the renal tubular enz ymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine. Antimicrobial combinations studied i ncluded gentamicin plus placebo and gentamicin plus ticarcillin/clavul anate (protocol 1); and gentamicin plus placebo, gentamicin plus piper acillin, and gentamicin plus ceftazidime (protocol 2). The antimicrobi al regimens were administered for 7 days. Eight subjects completed eac h treatment group. RESULTS: There were no significant differences betw een treatment groups with regard to urine creatinine excretion or seru m gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0. 039] and NAG [p = 0.337]) was decreased in the gentamicin plus ticarci llin/clavulanate treatment compared with that in the gentamicin plus p lacebo treatment. Increased enzymuria, as indicated by increased urine concentrations of AAP and NAG, was observed in the gentamicin plus ce ftazidime treatment (p < 0.05) compared with the other two treatments. CONCLUSIONS: Based on relative enzymuria, ticarcillin/clavulanate may be renal protective. Piperacillin neither potentiated nor ameliorated aminoglycoside-induced enzymuria. Since acute elevations in AAP and N AG reflect insults to the kidney, these studies suggest that ceftazidi me may enhance aminoglycoside-induced renal injury. Piperacillin had n o effect on enzymuria and would appear not to enhance or protect again st aminoglycoside-induced renal injury.