Efficacy of carbapenems and alternative antimicrobials for treating complicated urinary tract infections caused by third-generation cephalosporin-resistant gram-negative bacteria: A systematic review and meta-analysis of randomised controlled trials

Masayuki Maeda; Tomiko Sunaga; Miki Takenaka Sato; Takeshi Hasegawa; Hisashi Noma; Erika Ota

doi:10.1016/j.jiac.2024.05.001

Efficacy of carbapenems and alternative antimicrobials for treating complicated urinary tract infections caused by third-generation cephalosporin-resistant gram-negative bacteria: A systematic review and meta-analysis of randomised controlled trials

J Infect Chemother. 2024 May 4:S1341-321X(24)00127-2. doi: 10.1016/j.jiac.2024.05.001. Online ahead of print.

Authors

Masayuki Maeda¹, Tomiko Sunaga², Miki Takenaka Sato³, Takeshi Hasegawa⁴, Hisashi Noma⁵, Erika Ota⁶

Affiliations

¹ Division of Infection Control Sciences, Department of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo, Japan. Electronic address: m-maeda@pharm.showa-u.ac.jp.
² Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan.
³ Division of Pharmacotherapeutics, Department of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo, Japan.
⁴ Showa University Research Administration Center, Showa University, Tokyo, Japan.
⁵ Department of Data Science, The Institute of Statistical Mathematics, Tokyo, Japan.
⁶ Global Health Nursing, Graduate School of Nursing Science, St. Luke's International University, Tokyo, Japan; The Tokyo Foundation for Policy Research, Minato-ku, Tokyo, Japan.

PMID: 38705237
DOI: 10.1016/j.jiac.2024.05.001

Abstract

Background: Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking.

Objectives: This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens.

Methods: In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov, were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95 % confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I² statistics.

Results: Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95 % CI, 0.63-1.49; I² = 21 %; low certainty of evidence).

Conclusions: Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins.

Keywords: Carbapenem; antimicrobial resistance; antimicrobial stewardship; complicated urinary tract infection; extended-spectrum beta-lactamase.

Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.