{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:01:30Z","timestamp":1790096490333,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Carbapenems remain the standard treatment for infections caused by extended-spectrum \u03b2-lactamase\u2013producing Enterobacterales (ESBL-E), but their widespread use contributes to the emergence of carbapenem resistance. Cephamycins have been proposed as carbapenem-sparing alternatives because of their relative stability against ESBL-mediated hydrolysis; however, their clinical effectiveness remains uncertain. We aimed to compare the effectiveness of cephamycins versus carbapenems as definitive treatment for ESBL-E infections. Methods: We searched Scopus, PubMed, and Embase for studies comparing cephamycins with carbapenems for the treatment of ESBL-producing Enterobacterales infections, with the search conducted through January 2026. Observational studies and randomized trials comparing cephamycins (cefmetazole, flomoxef, cefoxitin) with carbapenems in adult patients with microbiologically confirmed ESBL-E infections were included. The primary outcome was all-cause mortality; secondary outcomes were clinical and microbiological cure. Risk of bias was assessed using ROBINS-I, and data were pooled using random-effects models. Results: Ten retrospective cohort studies (n = 653 for mortality) were included. Cephamycins were associated with a non-significant trend toward lower mortality compared with carbapenems (OR 0.48, 95% CI 0.22\u20131.03). Subgroup analyses suggested a potential benefit in Escherichia coli and urinary-source infections, whereas no advantage was observed in Klebsiella pneumoniae or non-urinary bloodstream infections. No significant differences were found for clinical or microbiological cure. The certainty of evidence was rated as very low. Conclusions: Cephamycins may represent a carbapenem-sparing option in carefully selected patients with low-risk ESBL-E infections, particularly urinary-source infections caused by E. coli. However, the current evidence is limited to retrospective observational studies with very low certainty and should be considered hypothesis-generating rather than practice-changing. Adequately powered randomized controlled trials are needed to confirm these findings.<\/jats:p>","DOI":"10.3390\/antibiotics15090935","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:28:43Z","timestamp":1790090923000},"page":"935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Risk-Stratified Effectiveness of Cephamycins Versus Carbapenems for ESBL-Producing Enterobacterales Infections: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-6634","authenticated-orcid":false,"given":"Giacomo","family":"Franceschi","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"},{"name":"Hesperia Hospital, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2970-1276","authenticated-orcid":false,"given":"Mattia","family":"Marchi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Cantergiani","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Orlando","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-464X","authenticated-orcid":false,"given":"Stefania","family":"Casolari","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-5759","authenticated-orcid":false,"given":"Erica","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-1459","authenticated-orcid":false,"given":"Andrea","family":"Bedini","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mussini","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Meschiari","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Azienda Ospedaliera-Universitaria of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jhin.2015.10.001","article-title":"Impact of infection with extended-spectrum \u03b2-lactamase-producing Escherichia coli or Klebsiella species on outcome and hospitalization costs","volume":"92","author":"Maslikowska","year":"2016","journal-title":"J. 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