Is the Combination of Piperacillin-Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta-analysis.
To evaluate the association of the development of acute kidney injury (AKI) when piperacillin-tazobactam is used in combination with vancomycin compared with vancomycin with or without a β-lactam.



Meta-analysis of 15 observational cohort studies.



A total of 3258 adult inpatients who received vancomycin + piperacillin-tazobactam versus vancomycin alone (10 studies); vancomycin + piperacillin-tazobactam versus vancomycin + β-lactam (four studies); or vancomycin + piperacillin-tazobactam versus vancomycin alone or vancomycin + other antibiotics (one study).



The PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases, as well as meeting proceedings, were searched (1966-June 1, 2016). Quality of studies was assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOQAS). The primary outcome of this meta-analysis was to evaluate the association of development of AKI with the combined use of piperacillin-tazobactam and vancomycin. A subgroup analysis was also performed that examined the outcome by comparison groups (vancomycin alone or vancomycin + β-lactam). Sensitivity analysis was performed to explore if the results differed based on removal of abstracts and removal of low-quality studies (NOQAS scores of 6 or lower). All analyses were performed using the random effects model. NOQAS scores for the 15 studies ranged from 3-7 points (of a total of 9). Overall, there was an association with the development of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin ± β-lactam (odds ratio [OR] 3.649, 95% confidence interval [CI] 2.157-6.174; I2= 83.5%, p<0.001). The association remained significant when abstracts were removed (OR 3.498, 95% CI 1.747-7.003, I2= 82.3%, p<0.001) and when low-quality studies were removed (OR 4.596, 95% CI 2.929-7.212, I2= 0%, p<0.001). The association for the development of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin alone was significant (OR 3.980, 95% CI 2.749-5.763, I2= 31.4%, p<0.001), although the association did not remain significant for the vancomycin + β-lactam subgroup (OR 3.029, 95% CI 0.942-9.738, I2= 82.3%, p=0.063).



Vancomycin + piperacillin-tazobactam was associated with an increased risk of AKI compared with vancomycin ± β-lactam. Practitioners need to be vigilant about this association when prescribing this combination of antibiotics.
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, St. John Hospital and Medical Center, Detroit, Michigan.
Christopher A
CA
Giuliano
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, St. John Hospital and Medical Center, Detroit, Michigan.
Chandni R
CR
Patel
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, St. John Hospital and Medical Center, Detroit, Michigan.
Pramodini B
PB
Kale-Pradhan
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D006801:Humans; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects; D000077725:Piperacillin, Tazobactam Drug Combination; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D014640:Vancomycin; D010397:Penicillanic Acid; D010878:Piperacillin
Piperacillin-tazobactam; Zosyn; acute kidney injury; nephrotoxicity; vancomycin