To evaluate the efficacy of piperacillin/tazobactam (PTZ) for the treatment of extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) urinary tract infections (UTIs). A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards on PubMed, MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central through July 2024. Studies providing efficacy data associated with PTZ in patients ≥18 years old experiencing an ESBL-PE UTI that documented clinical and microbiological cure data were included. A total of 577 articles were obtained for screening. After applying the inclusion and exclusion criteria, 7 studies comparing PTZ with carbapenems comprised of 1156 patient cases were analyzed. Piperacillin/tazobactam was found to be noninferior to carbapenems in the treatment of both uncomplicated and complicated UTI's caused by ESBL-PE. The observed noninferiority encompassed clinical response, clinical cure, and microbiological cure outcome metrics. Although not specifically evaluated in this systematic review, adverse effects associated with PTZ were found to be minimal and lesser in incidence than with the carbapenem comparators in aggregate. While a definitive dosing strategy remains elusive, a PTZ total daily dose of 13.5 g infused over 3 to 4 hours may be appropriate for this indication. Piperacillin/tazobactam may be an effective carbapenem-sparing agent for the treatment of ESBL-PE UTIs that show in-vitro susceptibility to PTZ. However, additional robust randomized clinical trials are still needed to validate the findings of this review and determine the best dosage regimen of PTZ for ESBL-PE UTIs.
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