Association between concomitant use of vancomycin-piperacillin/tazobactam and acute kidney injury in real-world...

The association between acute kidney injury (AKI) and the concomitant use of vancomycin with piperacillin-tazobactam (VPT), meropenem (VM), cefepime (VC), or monotherapy with vancomycin or piperacillin-tazobactam remains controversial. This study was conducted to compare the incidence of AKI in patients receiving VPT versus those treated with vancomycin in combination with other antibiotics or as monotherapy.

A comprehensive literature search was performed across PubMed, Embase, and the Cochrane library from inception up to November 30, 2025, to identify studies reporting AKI rates among patients receiving VPT or other vancomycin-based regimens. The primary outcome was the pooled incidence of AKI, which was analyzed using a random-effects model. Subgroup analyses were carried out according to geographic region and clinical setting.

Thirty-five studies encompassing 39, 554 patients were included in the final synthesis. The highest pooled incidence of AKI was observed in patients receiving VPT (25.50%, 95% CI: 23.00%-28.00%), followed by VC (16.50%, 95% CI: 12.90%- 20.10%) and VM (14.00%, 95% CI: 8.90-19.20). Lower incidence rates were reported with vancomycin monotherapy (8.10%, 95% CI: 5.80%-10.40%) and piperacillin- tazobactam alone (12.30%, 95% CI: 6.70%-17.90%). Subgroup analysis showed that ICU patients experienced significantly higher AKI rates when receiving VPT (33.80%, 95% CI: 29.80%-37.70%) compared to non-ICU patients (17.20%, 95% CI: 15.80% -18.60%), a trend also observed with piperacillin- tazobactam monotherapy (P < 0.05). Geographically, patients in Europe exhibited a markedly higher risk of AKI with VPT (41.30%, 95% CI: 29.10%-53.50%) than those in North America (25.40%, 95% CI: 22.80-28.10) or Asia (24.80%, 95% CI: 14.60-35.00). Nevertheless, this result from European population was only based on one study, it needs to be interpreted carefully. Similarly, the risk of nephrotoxicity with vancomycin monotherapy was higher in European populations (15.70%) compared to North American (8.40%) and Asian (4.00%) patients.

This study suggests that VPT is linked to the highest risk of AKI compared to other vancomycin-containing regimens, including beta-lactam combinations and monotherapies. These findings highlight the importance of prudent antibiotic selection and rigorous renal monitoring, particularly in critically ill patients.