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Does Combination Therapy With Vancomycin and Piperacillin-Tazobactam Increase the Risk of Nephrotoxicity Versus

Katherine E McQueen1, Dana W Clark1

  • 1Department of Pharmacy, Children's Healthcare of Atlanta, Atlanta, Georgia.

The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG
|October 8, 2016
PubMed

Insights

Combination therapy with vancomycin and piperacillin-tazobactam significantly increases pediatric nephrotoxicity risk compared to vancomycin alone. Higher vancomycin levels in the combination group further elevated this risk.

Area of Science:

  • Pediatric Nephrology
  • Infectious Diseases
  • Pharmacology

Background:

  • Vancomycin is a critical antibiotic for treating serious Gram-positive infections in children.
  • Piperacillin-tazobactam is frequently used in combination with vancomycin for broad-spectrum coverage.
  • The potential for increased nephrotoxicity with combination therapy requires careful evaluation.

Purpose of the Study:

  • To compare the incidence of nephrotoxicity in pediatric patients receiving vancomycin alone versus vancomycin plus piperacillin-tazobactam.
  • To identify risk factors associated with nephrotoxicity in these treatment groups, including ICU admission, vancomycin trough concentrations, and concomitant nephrotoxic agents.

Main Methods:

  • Retrospective, single-center cohort study involving 79 patients on vancomycin and 106 on vancomycin plus piperacillin-tazobactam.
  • Nephrotoxicity defined as ≥100% increase in serum creatinine or ≥0.5 mg/dL from baseline.
  • Fisher's exact test and relative risk calculations were used for comparisons.

Main Results:

  • Nephrotoxicity occurred in 3.8% of the vancomycin-only group versus 23.6% in the combination group (p=0.0001).
  • In the combination group, higher vancomycin trough concentrations (>15 mg/L) significantly increased nephrotoxicity risk (RR 5.22, p<0.0001).
  • No significant risk factors for nephrotoxicity were identified in the vancomycin-only group.

Conclusions:

  • Combination therapy with vancomycin and piperacillin-tazobactam is associated with a higher incidence of nephrotoxicity in pediatric patients.
  • Higher vancomycin trough concentrations are a significant risk factor for nephrotoxicity in patients receiving combination therapy.
  • Further investigation is warranted to fully elucidate risk factors and optimize antibiotic stewardship.

Keywords:
acute kidney injuryadverse drug effectnephrotoxicitypediatricpiperacillin-tazobactamvancomycin

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