Efficacy of carbapenems versus alternative antimicrobials for treating complicated urinary tract infections caused by antimicrobial-resistant Gram-negative bacteria: Protocol for a systematic review and meta-analysis

Abstract

Introduction Complicated urinary tract infections (cUTIs) are associated with poor prognosis. The widespread infection of multidrug-resistant Gram-negative uropathogens such as extended-spectrum beta-lactamase-producing bacteria has limited the efficacy of antibiotics used for treating cUTI. Considering the existence of antimicrobial-resistant (AMR) uropathogens, carbapenem is the last-resort antibiotic for cUTI. Given that carbapenem overuse has facilitated the spread of carbapenem-resistant Gram-negative bacteria, carbapenem dependence should be urgently reduced. However, improvement on the clinical outcomes of alternative antibiotics against cUTI caused by AMR uropathogens has not yet been systematically evaluated. Thus, this systematic review and meta-analysis aims to explore and compare the clinical outcomes of cUTI caused by AMR uropathogens between carbapenem and non-carbapenem antibiotics. Methods and analysis The study inclusion criteria will be considered based on the PICO model consisting the following elements: population - adult patients with cUTIs caused by Gram-negative uropathogens; intervention - non-carbapenem class of antimicrobial agents with in vitro activities against Gram-negative uropathogens; comparison - treatment of carbapenem class antibiotics; outcome - a clinical and microbiological cure. Relevant articles published until December 2022 will be systematically searched in February 2023, using electronic databases such as PubMed, the Cochrane Library, EMBASE and ClinicalTrials.gov. Two independent reviewers will screen the select literature and then assess the full-text article to meet the inclusion criteria. The risk of bias will be assessed using the Cochrane risk-of-bias assessment tool. The treatment effects of antibiotics will be estimated as a risk ratio with a 95% CI, using the random-effects model. Ethics and dissemination This protocol and systematic review will not include direct patient data; thus, informed consent will be waived. The results of this study will be published in an international peer-reviewed journal for wider information dissemination. PROSPERO registration number CRD42022356064.