{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:24:46Z","timestamp":1786965886428,"version":"build-2736575974"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Carbapenem-resistant Gram-negative (CRGN) pathogens\u2014including Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii\u2014are a major global health threat. Newer \u03b2-lactam agents including novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations and other recently introduced \u03b2-lactam agents have expanded treatment options. However, although current guidelines focus on their use as targeted therapy, their role in empirical treatment of suspected bacterial sepsis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this review we evaluate epidemiological studies, randomized trials, comparative observational studies, international guidelines, microbiological surveillance data on CRGN infections and clinical factors supporting consideration of empirical use of newer \u03b2-lactam agents in patients with sepsis at risk for CRGN infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Carbapenem resistance epidemiology varies substantially across regions and strongly affects the likelihood of CRGN infection. Key risk factors include prior CRGN colonization or infection, recent broad-spectrum antibiotic exposure, prolonged hospitalization and healthcare contact in high-prevalence settings. In sepsis, delayed effective antimicrobial therapy\u2014particularly in septic shock or severe immunosuppression\u2014is associated with poorer outcomes. However, indiscriminate empirical use of newer \u03b2-lactam agents may promote resistance and compromise stewardship efforts. Direct evidence supporting empirical use of these agents remains limited and is based largely on observational data and extrapolation from targeted-therapy studies. Empirical use of newer agents may be appropriate for carefully selected patients with a high probability of CRGN infection and clinical scenarios where delayed active therapy could have serious consequences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A risk-stratified, stewardship-integrated approach incorporating local epidemiology, patient-level risk factors, illness severity and rapid diagnostics may optimize timely effective therapy while preserving the long-term utility of these agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jacamr\/dlag174","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:37:07Z","timestamp":1785843427000},"source":"Crossref","is-referenced-by-count":0,"title":["When might we consider using the newer \u03b2-lactam agents as empirical therapy against presumed carbapenem-resistant gram-negative infections?"],"prefix":"10.1093","volume":"8","author":[{"given":"Stelios F","family":"Assimakopoulos","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Division of Infectious Diseases, University of Patras School of Medicine , Patras ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hygeia Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-9001","authenticated-orcid":false,"given":"Jes\u00fas","family":"Rodriguez-Bano","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena, Departamento de Medicina, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS)\/CSIC, Seville ,","place":["Spain"]},{"name":"CIBERINFEC, Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markos","family":"Marangos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Division of Infectious Diseases, University of Patras School of Medicine , Patras ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L","family":"Daikos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hygeia Hospital , Athens ,","place":["Greece"]},{"name":"National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"2026081706323607900_dlag174-B1","author":"World Health Organization"},{"key":"2026081706323607900_dlag174-B2","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global 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