Background Flomoxef is active against extended–spectrum beta–lactamase (ESBL)–producing bacteria, but its clinical effectiveness has not been compared with cefmetazole. This study aimed to compare the utility of the two drugs in treating urinary tract infection (UTI) by integrating in vitro data with a retrospective analysis of two real–world databases. Methods The susceptibility rates of third–generation cephalosporin–resistant Escherichia coli and Klebsiella pneumoniae to flomoxef and cefmetazole were compared using comprehensive national antimicrobial resistance surveillance data. Combinational antimicrobial activities against an ESBL–producing multidrug–resistant bacterial strain were tested by diagonal measurement of n–way drug interactions (DiaMOND), an innovative method to assess antimicrobial interactions in vitro. The effectiveness of the two drugs in treating UTIs was compared using hospital stay duration as the primary outcome obtained from the Japan Medical Data Center (JMDC) Claims Database. Results Third–generation cephalosporin–resistant E. coli and K. pneumoniae, including ESBL–producing strains, were similarly susceptible to flomoxef and cefmetazole. In vitro assessment of combinational antimicrobial activities against an ESBL–producing multidrug–resistant strain revealed that both drugs showed similar antimicrobial interaction patterns. JMDC Claims data analysis showed that the median time of hospital stay duration was 11 days (95% confidence interval [CI]: 11–11) in the cefmetazole group and 4 days (95% CI: 3–5) in the flomoxef group, significantly shorter in the latter (log–rank test, P < 0.001). In addition, the flomoxef group had a significantly lower frequency of adverse events such as Clostridioides difficile infection. Conclusions Flomoxef exhibits effectiveness that is comparable to cefmetazole in treating UTI without major concerns about adverse events such as C. difficile infection or renal impairment. This evidence endorses flomoxef as a viable treatment option for UTIs in locales with high prevalence of ESBL–prodcing strains.

The authors have declared no competing interest.

This work was supported by Japan Agency for Medical Research and Development (AMED) [grant number JP23wm0325037, JP24fk0108665, JP24fk0108683, JP24fk0108712, JP24fk0108642, JP24gm1610003, JP24wm0225029, JP24wm0225022, and JP24gm1610013]　and JSPS KAKENHI Grant (23H02634). The funders had no role in the study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit for publication.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This part of the study was approved by the Ethics Committee of Tokushima University Hospital, protocol number: 4492.

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All data produced in the present study are available upon reasonable request to the authors.