Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various β-lactam antibiotics

David E. Nix, Jennifer K. Thomas, William T. Symonds, J. Michael Spivey, John H. Wilton, Nick C. Gagliardi, Jerome J. Schentag

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

OBJECTIVE: To determine the propensity of β-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: 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-β-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.

Original languageEnglish (US)
Pages (from-to)696-703
Number of pages8
JournalAnnals of Pharmacotherapy
Volume31
Issue number6
StatePublished - Jun 1997

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Lactams
CD13 Antigens
Gentamicins
Anti-Bacterial Agents
Hexosaminidases
Aminoglycosides
Ticarcillin
Kidney
Clavulanic Acid
Piperacillin
Ceftazidime
Placebos
Creatinine
Therapeutics
Urine
Urine Specimen Collection
Wounds and Injuries
Healthy Volunteers

Keywords

  • β- lactam
  • Ceftazidime
  • Enzymuria
  • Gentamicin
  • Nephrotoxicity
  • Ticarcillin/clavulanate

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Nix, D. E., Thomas, J. K., Symonds, W. T., Spivey, J. M., Wilton, J. H., Gagliardi, N. C., & Schentag, J. J. (1997). Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various β-lactam antibiotics. Annals of Pharmacotherapy, 31(6), 696-703.

Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various β-lactam antibiotics. / Nix, David E.; Thomas, Jennifer K.; Symonds, William T.; Spivey, J. Michael; Wilton, John H.; Gagliardi, Nick C.; Schentag, Jerome J.

In: Annals of Pharmacotherapy, Vol. 31, No. 6, 06.1997, p. 696-703.

Research output: Contribution to journalArticle

Nix, DE, Thomas, JK, Symonds, WT, Spivey, JM, Wilton, JH, Gagliardi, NC & Schentag, JJ 1997, 'Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various β-lactam antibiotics', Annals of Pharmacotherapy, vol. 31, no. 6, pp. 696-703.
Nix, David E. ; Thomas, Jennifer K. ; Symonds, William T. ; Spivey, J. Michael ; Wilton, John H. ; Gagliardi, Nick C. ; Schentag, Jerome J. / Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various β-lactam antibiotics. In: Annals of Pharmacotherapy. 1997 ; Vol. 31, No. 6. pp. 696-703.
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abstract = "OBJECTIVE: To determine the propensity of β-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: 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-β-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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AU - Nix, David E.

AU - Thomas, Jennifer K.

AU - Symonds, William T.

AU - Spivey, J. Michael

AU - Wilton, John H.

AU - Gagliardi, Nick C.

AU - Schentag, Jerome J.

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N2 - OBJECTIVE: To determine the propensity of β-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: 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-β-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.

AB - OBJECTIVE: To determine the propensity of β-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: 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-β-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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KW - Nephrotoxicity

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