{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:20:03Z","timestamp":1784035203817,"version":"3.55.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373966"],"award-info":[{"award-number":["82373966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Changsha Natural Science Foundation","award":["kq2208360"],"award-info":[{"award-number":["kq2208360"]}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ9329"],"award-info":[{"award-number":["2024JJ9329"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"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>Objectives<\/jats:title>\n                    <jats:p>To develop a population pharmacokinetic (PPK) model of polymyxin B for intravenous (IV) and combined intravenous plus inhaled (IV\u200a+\u200aIH) administration in critically ill patients, and evaluate the association between plasma 24-h steady-state area under concentration\u2013time curve to minimum inhibitory concentration ratio (AUCss,24h\/MIC) and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective observational cohort study, adults with multidrug-resistant Gram-negative bacterial infections receiving polymyxin B\u200a \u2265\u200a48\u2005h were enrolled and assigned to IV or IV\u200a+\u200aIH groups. Plasma samples were analysed by validated HPLC\u2013MS\/MS. PPK models were developed with NONMEM. Clinical efficacy at the end of treatment was blindly assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty-three patients were enrolled (IV, n\u200a=\u200a22; IV\u200a+\u200aIH, n\u200a=\u200a21), with an overall clinical success rate of 66.7%. A two-compartment PPK model best described the data. The typical clearance was 2.61 L\/h, with creatinine clearance and total bile acids identified as significant covariates. In the overall cohort, no significant differences in AUCss,24h or AUCss,24h\/MIC were observed between clinical success and failure (P\u200a=\u200a0.591 and 0.143, respectively). In the IV group, AUCss,24h\/MIC was significantly higher in responders (P\u200a=\u200a0.005), and an ROC analysis suggested an exploratory efficacy threshold of 94.4; AUCss,24h showed a non-significant trend (P\u200a=\u200a0.076). No exposure\u2013response relationship was observed in the IV\u200a+\u200aIH group (P\u200a=\u200a0.398 and 0.495, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma AUCss,24h\/MIC appears to be associated with clinical efficacy during IV monotherapy but not in IV\u200a+\u200aIH regimens, possibly due to high pulmonary exposure. Plasma-based PK\/PD targets should be applied cautiously when inhalation is added.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag238","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:00:25Z","timestamp":1784034025000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of adjunctive inhalation on the association between plasma AUC\/MIC of polymyxin B and clinical efficacy in MDR gram-negative infections"],"prefix":"10.1093","volume":"81","author":[{"given":"Shengnan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital of Central South University , Changsha, Hunan 410013 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital of Central South University , Changsha, Hunan 410013 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