{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T12:04:25Z","timestamp":1773749065894,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BioVersys AG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Polymyxin B has been used for many years to treat Acinetobacter baumannii, but little is known about its pharmacodynamics (PD). We aimed to describe the PD of polymyxin B in treating A. baumannii infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the murine neutropenic thigh and lung infection models we determined the magnitude of the pharmacokinetic (PK)\/PD index correlating with efficacy for eight A. baumannii strains. PD was analysed using the Emax model to determine PD targets. Using published human PK data the PTAs were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the thigh infection model, stasis, 1-log10 and 2-log10 kill were reached for all strains. Median (range) fAUC\/MIC (area under the unbound concentration\u2013time curve divided by the MIC) targets for stasis, 1-log10 kill and 2-log10 kill were 2.1 (1.0\u201311), 2.9 (1.0\u201315) and 4.0 (1.1\u201320), respectively. In contrast, in the lung model, 2-log10 kill was reached in 2\/8 strains only, and there was insufficient killing at tolerated exposures to determine PD fAUC\/MIC targets. For the standard human dosing regimen, PTAs derived from the thigh model were inadequate at the USCAST (United States Committee on Antimicrobial Susceptibility Testing) clinical breakpoint and a protein binding of 90%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Whereas polymyxin B treatment had good efficacy in the murine thigh infection model, in the lung infection model its effect was limited. PD targets, with MICs of circulating A. baumannii isolates of \u22642\u2005mg\/L, are not reached with a standard human dosing regimen and will probably exceed threshold values for toxicity. These data suggest that the efficacy of polymyxin B as monotherapy for A. baumannii infections is questionable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag097","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:25:21Z","timestamp":1772454321000},"source":"Crossref","is-referenced-by-count":0,"title":["The pharmacodynamics of polymyxin B in\n                    <i>Acinetobacter baumannii<\/i>\n                    in murine thigh and lung infection models"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9209-0178","authenticated-orcid":false,"given":"Sanne","family":"van den Berg","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam , Rotterdam ,","place":["The Netherlands"]},{"name":"CATOR, Center for Antimicrobial Treatment Optimization Rotterdam , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Pieren","sequence":"additional","affiliation":[{"name":"BioVersys AG , Basel ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-638X","authenticated-orcid":false,"given":"Sebastiaan D T","family":"Sassen","sequence":"additional","affiliation":[{"name":"CATOR, Center for Antimicrobial Treatment Optimization Rotterdam , Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Hospital Pharmacy, Erasmus MC University Medical Center Rotterdam , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem A M","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina S C","family":"Boonman","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn E","family":"Dale","sequence":"additional","affiliation":[{"name":"BioVersys AG , Basel ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-6251","authenticated-orcid":false,"given":"Anouk E","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam , Rotterdam ,","place":["The Netherlands"]},{"name":"CATOR, Center for Antimicrobial Treatment Optimization Rotterdam , Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Medical Microbiology, Haaglanden Medisch Centrum , The Hague ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"2026031707165996300_dkag097-B1","doi-asserted-by":"publisher","first-page":"711","DOI":"10.2217\/fmb.13.39","article-title":"Pharmacology of polymyxins: new insights into an \u2018old\u2019 class of antibiotics","volume":"8","author":"Velkov","year":"2013","journal-title":"Future Microbiol"},{"key":"2026031707165996300_dkag097-B2","doi-asserted-by":"publisher","first-page":"R27","DOI":"10.1186\/cc3995","article-title":"Toxicity of polymyxins: a systematic review of the evidence from old and recent studies","volume":"10","author":"Falagas","year":"2006","journal-title":"Crit 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