Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin With Concomitant Piperacillin-Tazobactam Versus Other Beta-Lactams: A Systematic Review and Meta-Analysis

Abstract

Objectives: To explore whether vancomycin (VAN) plus piperacillin-tazobactam (PTZ) was associated with an increased risk of acute kidney injury (AKI) compared with VAN plus other beta-lactams (BLs) or monotherapy in critically ill patients, where the evidence remains controversial. Data sources: PubMed, Cochrane, Web of Science, and Embase were searched from inception to June 2024. Study selection: Studies comparing the risk of AKI with one group receiving VAN+PTZ, and other groups receiving VAN plus other BLs, or monotherapy in critically ill. Data synthesis: This analysis included 20 articles with 28 243 participants. The majority of included studies were retrospective (95%, 19/20) and had moderate risks of bias (80.0%, 16/20). The results indicated VAN+PTZ was associated with a significantly higher risk of AKI compared with VAN plus other BLs (OR = 1.66, 95% CI = 1.42-1.94, P < 0.001). Subgroup analyses showed that compared with adults, children were associated with a higher risk of AKI when receiving VAN+PTZ (OR = 3.16 vs 1.59). Also, VAN+PTZ was associated with a significantly higher risk of severe stage 2 to 3 AKI than VAN plus other BLs (OR = 1.63, 95% CI = 1.28-2.06, P < 0.001). No significant difference was identified in mortality, dialysis, time to AKI, and length of stay between patients receiving VAN plus PTZ and other combinations. Conclusions: In critically ill, VAN plus PTZ was associated with an increased risk of AKI and severe stage 2 to 3 AKI compared with VAN plus other BLs, especially in children. However, more high-quality multicenter, prospective cohort studies, and randomized controlled studies are needed.

Keywords: acute kidney injury; beta-lactams; critically ill; piperacillin-tazobactam; vancomycin.

Figure 1.

Flow diagram.

Figure 2.

Forest plot demonstrating the odds of AKI with VAN+PTZ versus VAN+other BLs or alone. Data are expressed as odds ratio and 95% confidence intervals. In studies (Blevins AM, Hundeshagen G, Kang S and Schreier DJ) including VAN+PTZ, VAN+other BLs, and VAN monotherapy, VAN+PTZ may appear more than once in pairwise comparisons; thus, to avoid duplication in the overall estimate, only one comparison per study was included in the total, combining VAN+other BLs and monotherapy as a single reference group. Chen AY, 2023a represents the comparison groups of VAN+PTZ versus VAN+FEP; Chen AY, 2023b represents the comparison groups of VAN+PTZ versus VAN+MEM; Hundeshagen G, 2017a represents the population of adult; Hundeshagen G, 2017b represents the population of children. BLs, beta-lactams: other BLs was defined as BLs other than PTZ. Abbreviations: AKI, acute kidney injury; VAN, vancomycin; PTZ, piperacilline-tazobactam. Note. Chen AY, 2023a and Chen AY, 2023b represent two subgroup comparisons within the same study: VAN+PTZ vs. VAN+FEP (2023a) and VAN+PTZ vs. VAN+MEM (2023b). Hundeshagen G, 2017a and Hundeshagen G, 2017b represent two subgroup comparisons within the same study: population of adult (2017a) and population of children (2017b)

Figure 3.

Forest plot demonstrating the odds of severe stage 2 to 3 AKI with VAN+PTZ versus VAN plus other BLs or monotherapy. Data are expressed as odds ratio and 95% confidence intervals. In studies (Blevins AM, Hundeshagen G, Kang S and Schreier DJ) including VAN+PTZ, VAN+other BLs, and VAN monotherapy, VAN+PTZ may appear more than once in pairwise comparisons; thus, to avoid duplication in the overall estimate, only one comparison per study was included in the total, combining VAN+other BLs and monotherapy as a single reference group. Chen AY, 2023a represents the comparison groups of VAN+PTZ versus VAN+FEP; Chen AY, 2023b represents the comparison groups of VAN+PTZ versus VAN+MEM; Hundeshagen G, 2017a represents the population of adult; Hundeshagen G, 2017b represents the population of children. BLs = beta-lactams: other BLs was defined as BLs other than PTZ. Abbreviations: AKI, acute kidney injury; VAN, vancomycin; PTZ, piperacilline-tazobactam. Note. Chen AY, 2023a and Chen AY, 2023b represent two subgroup comparisons within the same study: VAN+PTZ vs. VAN+FEP (2023a) and VAN+PTZ vs. VAN+MEM (2023b). Hundeshagen G, 2017a and Hundeshagen G, 2017b represent two subgroup comparisons within the same study: population of adult (2017a) and population of children (2017b)

Figure 4.

Forest plot demonstrating the odds of AKI with VAN+PTZ versus VAN plus other BLs (Subgroup analysis of studies based on population: adults, children). Data are expressed as odds ratio and 95% confidence intervals. Hundeshagen G, 2017a represents the population of adult; Hundeshagen G, 2017b represents the population of children. BLs = beta-lactams: other BLs was defined as BLs other than PTZ. Abbreviations: AKI, acute kidney injury; VAN, vancomycin; PTZ, piperacilline-tazobactam. Note. Hundeshagen G, 2017a and Hundeshagen G, 2017b represent two subgroup comparisons within the same study: population of adult (2017a) and population of children (2017b)