Is the Combination of Piperacillin-Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta-analysis.

STUDY OBJECTIVE: 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.

DESIGN: Meta-analysis of 15 observational cohort studies.

PATIENTS: 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).

MEASUREMENTS AND MAIN RESULTS: 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).

CONCLUSION: 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.