{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:29:20Z","timestamp":1790342960986,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009210","name":"Food and Drug Administration","doi-asserted-by":"publisher","award":["75F40121C00184"],"award-info":[{"award-number":["75F40121C00184"]}],"id":[{"id":"10.13039\/100009210","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sulbactam dosing for Acinetobacter baumannii infections has not been standardized due to limited available pharmacokinetics\/pharmacodynamics (PK\/PD) data. Herein, we report a comprehensive PK\/PD analysis of ampicillin-sulbactam against A. baumannii pneumonia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Twenty-one A. baumannii clinical isolates were tested in the neutropenic murine pneumonia model. For dose-ranging studies, groups of mice were administered escalating doses of ampicillin-sulbactam. Changes in log10cfu\/lungs relative to 0 h were assessed. Dose-fractionation studies were performed. Estimates of the percentage of of time during which the unbound plasma sulbactam concentrations exceeded the MIC (%fT\u200a&amp;gt;\u200aMIC) required for different efficacy endpoints were calculated. The probabilities of target attainment (PTA) for the 1-log kill plasma targets were estimated following clinically utilized sulbactam regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Dose-fractionation studies demonstrated time-dependent kill. Isolates resistant to both sulbactam and meropenem required three times the exposures to achieve 1-log kill; median [IQR] %fT\u200a&amp;gt;\u200aMIC of 60.37% [51.6\u201366.8] compared with other phenotypes (21.17 [16.0\u201332.9] %fT\u200a&amp;gt;\u200aMIC). Sulbactam standard dose (1 g q6h, 0.5 h infusion) provided &amp;gt;90% PTA up to MIC of 4 mg\/L. Sulbactam 3 g q8h, 4 h inf provided greater PTA for isolates with sulbactam-intermediate susceptibility (8 mg\/L, 100% versus 86% following the standard dose). Despite the higher exposure following 3 g q8h, 4 h inf, PTA was \u226457% among sulbactam-resistant\/meropenem-resistant isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Sulbactam standard dose is a valuable regimen across sulbactam-susceptible isolates while the high-dose extended-infusion provides additional benefit against sulbactam-intermediate isolates. Given that most of the sulbactam-resistant A. baumannii isolates are meropenem-resistant, high-dose prolonged-infusion regimens are not expected to be effective as monotherapy against infections due to these isolates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae218","type":"journal-article","created":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T13:50:23Z","timestamp":1721483423000},"page":"2227-2236","source":"Crossref","is-referenced-by-count":16,"title":["Ampicillin-sulbactam against <i>Acinetobacter baumannii<\/i> infections: pharmacokinetic\/pharmacodynamic appraisal of current susceptibility breakpoints and dosing recommendations"],"prefix":"10.1093","volume":"79","author":[{"given":"Yasmeen","family":"Abouelhassan","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-3126","authenticated-orcid":false,"given":"Joseph L","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4148-0165","authenticated-orcid":false,"given":"David P","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"},{"name":"Division of Infectious Diseases, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2524-352X","authenticated-orcid":false,"given":"Kamilia","family":"Abdelraouf","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital 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