{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:12:34Z","timestamp":1784077954900,"version":"3.55.0"},"reference-count":124,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-B-059"],"award-info":[{"award-number":["2022-PUMCH-B-059"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["UBJ11756"],"award-info":[{"award-number":["UBJ11756"]}]},{"name":"Peking Union Medical College Hospital Outstanding Young Talent Development Program","award":["2022-PUMCH-B-059"],"award-info":[{"award-number":["2022-PUMCH-B-059"]}]},{"name":"Peking Union Medical College Hospital Outstanding Young Talent Development Program","award":["UBJ11756"],"award-info":[{"award-number":["UBJ11756"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Achieving pharmacokinetic\/pharmacodynamic (PK\/PD) targets is critical for improving treatment success, particularly in critically ill patients. This study investigates the role of inflammatory biomarkers and their influence on the PK\/PD characteristics of polymyxin B (PMB) in patients with extensively drug-resistant Gram-negative (XDR-GN) bacterial nosocomial pneumonia. Methods: Serial blood and\/or bronchoalveolar lavage fluid (BALF) samples were collected at specified time points and analyzed for PMB and\/or inflammatory biomarkers, including IL-6 and IL-10. Clinical data were also recorded, and their correlations with PK parameters were further analyzed. Results: Among the 27 enrolled patients, 22 (81.5%) achieved treatment success. The pharmacokinetic parameters of PMB included a maximum plasma concentration (Cmax) of 8.3 \u00b5g\/mL, clearance (CL) of 1.55 L\/h, volume of distribution (Vd) of 30.44 L, half-life (t1\/2) of 19.56 h, steady-state area under the plasma concentration\u2013time curve from time 0 to 24 h (AUCss,0\u201324h) of 110.08 h\u00b7\u00b5g\/mL, and a plasma protein-binding ratio of 85.53%. The AUCss,0\u201324h metric was identified as a robust predictor of clinical efficacy, with an optimal cutoff value of 77.27 h\u00b7\u00b5g\/mL. Notably, 48.15% of patients achieved the target AUCss,0\u201324h range of 50\u2013100 h\u00b7\u00b5g\/mL, with 76.95% of these patients attaining treatment success. Another 48.15% of patients exceeded this target, and 92.31% of this subgroup achieved treatment success. PMB demonstrated limited pulmonary penetration, with an epithelial lining fluid (ELF)\/plasma ratio of 15.69% [16.86, 18.15]. Furthermore, TNF-\u03b1 and the IL-6\/IL-10 ratio were significantly correlated with PMB PK parameters. Conclusions: Our and others\u2019 studies suggest heterogeneity of PMB PK parameters in critically ill patients. The majority of critically ill patients achieved or surpassed the recommended PK\/PD targets and attained treatment success through intravenous administration of PMB at a simplified fixed dose. However, PMB did not achieve satisfactory pulmonary concentrations, suggesting that its efficacy may involve alternative mechanisms. The modulation of inflammatory responses may play a pivotal role in the treatment of severe infections, highlighting the potential for biomarker-guided therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ph18040586","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T20:50:46Z","timestamp":1744923046000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biomarker-Driven Pharmacokinetics and Efficacy of Polymyxin B in Critically Ill Patients with XDR-GN Pneumonia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-4009","authenticated-orcid":false,"given":"Wei","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxiang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1086\/429323","article-title":"Colistin: The pharmacokinetics\/pharmacodynamics of systemically administered revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections","volume":"40","author":"Falagas","year":"2005","journal-title":"Clin. 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