{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:04Z","timestamp":1785409804318,"version":"3.56.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["UKRI885"],"award-info":[{"award-number":["UKRI885"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      is a high-priority pathogen with increasing antimicrobial resistance levels, requiring combination treatment. We aimed to develop a pharmacokinetic-pharmacodynamic model of meropenem with colistin\/polymyxin B against\n                      <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                      based on a systematic review of time-kill experiments to inform the effectiveness of this combination. PubMed was systematically searched for all studies describing time-kill experiments of meropenem and colistin\/polymyxin B combinations against A.\n                      <jats:italic toggle=\"yes\">baumannii<\/jats:italic>\n                      . Time-kill data and strain metadata were extracted. A pharmacokinetic-pharmacodynamic model with logistic growth, sigmoidal Emax killing functions of monotherapies, time-dependent attenuation of drug effect, and general pharmacodynamic interaction for the combination effect was fitted. Simulations were performed to produce dose recommendations. A total of 21 eligible papers were found reporting data from 369 experiments on 53 strains. Minimum inhibitory concentration (MIC) on EC50 (concentration achieving half-maximum killing), inoculum on Emax (maximum killing rate), and beta-lactamases on Emax for meropenem were covariates and both drugs. EC50 of both drugs included interisolate variability. The model showed that colistin\/polymyxin B increased meropenem Emax and decreased its EC50. No interisolate variability in the interaction was supported by the model. Simulations showed that in pneumonia, undetectable growth at 24 h can be achieved with a probability of &gt;90% only in strains with meropenem MIC \u226416 mg\/L. The model suggests that colistin\/polymyxin B enhances meropenem activity across a diverse set of strains but does not achieve adequate target attainment in resistant strains (colistin\/polymyxin B MIC \u22651 mg\/L and\/or meropenem MIC &gt;8 mg\/L). The presence of acquired beta-lactamases reduces the effect of meropenem.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00274-26","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:25:48Z","timestamp":1781101548000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic-pharmacodynamic modeling using combined time-kill data for meropenem and colistin or polymyxin B combination effects in\n                    <i>Acinetobacter baumannii<\/i>"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6475-7801","authenticated-orcid":true,"given":"Hiie","family":"Soeorg","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001mm6w73","id-type":"ROR","asserted-by":"publisher"}],"name":"Great Ormond Street Institute of Child Health, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihong","family":"Lyu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001mm6w73","id-type":"ROR","asserted-by":"publisher"}],"name":"Great Ormond Street Institute of Child Health, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-4559","authenticated-orcid":true,"given":"Frank","family":"Kloprogge","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001mm6w73","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Global Health, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-7173","authenticated-orcid":true,"given":"Joseph F.","family":"Standing","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001mm6w73","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, University College London","place":["London, United Kingdom"]},{"name":"Department of Pharmacy, Great Ormond Street Hospital for Children","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.46.2200845"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2025.10.019"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S172137"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.10.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01230-13"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2016.07.024"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.02.004"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw355"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01989-18"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2200131"},{"key":"e_1_3_4_12_2","unstructured":"The European Committee on Antimicrobial Susceptibility Testing. 2026. 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