{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:52:27Z","timestamp":1781866347547,"version":"3.54.5"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shanghai Talent Awards","award":["LJ2016-01"],"award-info":[{"award-number":["LJ2016-01"]}]},{"name":"Shanghai Science and Technology Innovation Action Plan","award":["23YF1404000"],"award-info":[{"award-number":["23YF1404000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cefoperazone-sulbactam, a \u03b2-lactam\/\u03b2-lactamase inhibitor combination, is widely used against ESBL-producing Gram-negative pathogens. This study investigated the in vivo pharmacokinetics\/pharmacodynamics (PK\/PD) of 1:1 and 2:1 cefoperazone-sulbactam formulations in neutropenic murine thigh and lung infection models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eleven ESBL-producing Gram-negative isolates with varying MICs were used to establish murine thigh and lung infection models. The plasma and epithelial lining fluid (ELF) pharmacokinetics of cefoperazone and sulbactam were evaluated over a wide dose range. Five dose-fractionation experiments were conducted to identify the PK\/PD index most correlated with efficacy, and dose\u2013escalation to determine PK\/PD targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All isolates exhibited cefoperazone MICs\u200a\u2265\u200a64\u2005mg\/L, reduced by 8- to 16-fold by sulbactam at a 1:1 or 2:1 ratio. Cefoperazone and sulbactam showed linear pharmacokinetics across the dose range, well described by a two-compartmental model. Plasma protein binding was 57% for cefoperazone and 3% for sulbactam. ELF penetration was 0.12 for cefoperazone and 0.21 for sulbactam, which were used to determine the ELF-based targets. PK\/PD targets reflecting the primary active component against each pathogen were reported. Cefoperazone %fT\u200a&amp;gt;\u200aMIC was used as the PK\/PD index for E. coli and K. pneumoniae, the magnitude for 1-log10 cfu bacterial reduction was 50.3% (1:1) and 51.3% (2:1) in the thigh infection model, 52.4% (1:1) and 75.6% (2:1) in the lung infection model. For A. baumannii, sulbactam was identified as the primary active component, and the 1-log10 cfu %fT\u200a&amp;gt;\u200aMIC target for sulbactam was 68.7%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cefoperazone-sulbactam demonstrated strong in vivo antibacterial activity against the 11 tested isolates. This study established PK\/PD targets under varied conditions, providing a valuable foundation for optimizing the clinical application of cefoperazone-sulbactam.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag214","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:22:24Z","timestamp":1780917744000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and pharmacodynamics of cefoperazone\/sulbactam in neutropenic murine lung and thigh infection models against Gram-negative organisms"],"prefix":"10.1093","volume":"81","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]},{"name":"Key Laboratory of Antibiotic Clinical Pharmacology of the National Health Commission , Huashan Hospital, Fudan University, Shanghai 200040 ,","place":["China"]},{"name":"Joint Laboratory of Hospital & 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