Background: Recent literature has demonstrated an increased incidence of acute kidney injury with combinations of vancomycin and piperacillin/tazobactam. The objective of this meta-analysis was to assess acute kidney injury with this combination therapy.
Methods: We performed a systematic literature review and meta-analysis using keywords of vancomycin, piperacillin, and kidney-related terms. Relevant studies in English were identified by searching Pubmed/Medline, Embase, Web of Science, and Cochrane from inception to May 2016, and manual searches of reference lists. Abstracts from conference proceedings and case reports were reviewed, but excluded. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model in RevMan 5.3.
Results: We identified 9 studies with 1772 patients to be included in the meta-analysis. Four studies compared vancomycin plus piperacillin/tazobactam to vancomycin monotherapy, while four studies compared to vancomycin plus cefepime or meropenem and one compared to piperacillin-tazobactam monotherapy. The overall incidence of acute kidney injury was 16% (284/1772); 20.4% (215/1054) for vancomycin plus piperacillin-tazobactam and 9.6% (69/718) for comparator. Overall odds ratio was 2.84 (95% CI 1.92-4.18, p<0.00001; I2=28%, p=0.20) versus any comparator (Figure 1). Odds ratios versus vancomycin monotherapy or vancomycin plus cefepime or meropenem were similar at OR 2.79 (95%CI 1.68-4.62, p=<0.0001; I2=14%, p=0.32) and OR 2.72 (95%CI 1.34-5.53, p=0.006; I2=54%, p=0.09), respectively.
Conclusion: Available data suggest that the combination of vancomycin plus piperacillin/tazobactam increases the odds of acute kidney injury over vancomycin monotherapy and vancomycin plus cefepime or meropenem. Confounding by indication and publication bias remain issues with these observational studies. Future comparative safety studies may help to clarify any association.
Merck (Cubist): Research , Research grant
D. Dosa, None
T. P. Lodise, Allergan/Merck/Medicines Company: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
K. Laplante, Merck (Cubist): Consultant and Scientific Advisor , Research support
Pfizer: Consultant and Scientific Advisor , Research support
Allergan (Forest): Consultant and Scientific Advisor , Research support
The Medicines Company: Consultant and Scientific Advisor , Research support
Melinta: Consultant and Scientific Advisor , Research support