Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various beta-lactam antibiotics.
OBJECTIVE
To determine the propensity of beta-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria.


METHODS
Two open, randomized, double-blind, parallel-group studies were conducted in young, healthy, male volunteer subjects. Using a common protocol, 24-hour urine collections were analyzed for the renal tubular enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine. Antimicrobial combinations studied included gentamicin plus placebo and gentamicin plus ticarcillin/clavulanate (protocol 1); and gentamicin plus placebo, gentamicin plus piperacillin, and gentamicin plus ceftazidime (protocol 2). The antimicrobial regimens were administered for 7 days. Eight subjects completed each treatment group.


RESULTS
There were no significant differences between treatment groups with regard to urine creatinine excretion or serum gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0.039] and NAG [p = 0.337]) was decreased in the gentamicin plus ticarcillin/clavulanate treatment compared with that in the gentamicin plus placebo treatment. Increased enzymuria, as indicated by increased urine concentrations of AAP and NAG, was observed in the gentamicin plus ceftazidime 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 NAG reflect insults to the kidney, these studies suggest that ceftazidime may enhance aminoglycoside-induced renal injury. Piperacillin had no effect on enzymuria and would appear not to enhance or protect against aminoglycoside-induced renal injury.
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D E
DE
Clinical Pharmacokinetics Laboratory, Millard Fillmore Health System, State University of New York at Buffalo, USA.
Thomas
J K
JK
Symonds
W T
WT
Spivey
J M
JM
Wilton
J H
JH
Gagliardi
N C
NC
Schentag
J J
JJ
D000118:Acetylglucosaminidase / Q000652:urine*; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D018826:CD13 Antigens / Q000652:urine*; D002442:Ceftazidime / Q000008:administration & dosage / Q000494:pharmacology; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013982:Ticarcillin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D005839:Gentamicins; D019818:Clavulanic Acid; D002442:Ceftazidime; D000118:Acetylglucosaminidase; D018826:CD13 Antigens; D013982:Ticarcillin; D010878:Piperacillin