{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:39:10Z","timestamp":1791859150555,"version":"4.3.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RC-2024-2790678"],"award-info":[{"award-number":["RC-2024-2790678"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To assess the impact of attaining aggressive \u03b2-lactam (BL) pharmacokinetic-pharmacodynamic (PK\/PD) targets on clinical efficacy in critically ill orthotopic liver transplant (OLT) recipients with documented early gram-negative infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study prospectively enrolled OLT recipients admitted to the posttransplant intensive care unit between June 2021 and May 2024; they had documented gram-negative infections treated with targeted therapy continuous infusion (CI) BLs and underwent therapeutic drug monitoring (TDM)-guided BL dosing adjustment within the first 72\u2005hours. Aggressive PK\/PD target attainment was measured. Multivariate logistic regression analyses were performed to test independent variables associated with 30-day resistance occurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty critically ill OLT recipients were treated with CI BL in monotherapy (n = 34) or combination (n = 16) therapy for documented gram-negative infections No significant difference in clinical\/microbiological outcome emerged between monotherapy and combination therapy. In 4 patients (8.0%), resistance developed within 30 days. At multivariate analysis, failure in attaining an aggressive BL PK\/PD target emerged as the only independent predictor of 30-day resistance development (odds ratio, 14.33 [95% confidence interval, 1.46\u2013140.53]; P = .02).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Attaining an aggressive PK\/PD target with CI BLs in critically ill OLT recipients with documented gram-negative infections could represent an effective strategy for minimizing resistance occurrence to the selected BL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf048","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T15:17:29Z","timestamp":1737645449000},"page":"e875-e885","source":"Crossref","is-referenced-by-count":8,"title":["Impact of Attaining an Aggressive Pharmacokinetic-Pharmacodynamic Target on the Clinical Efficacy of Continuous Infusion \u03b2-Lactam Therapy for Early Posttransplant Gram-Negative Infections in Critically Ill Orthotopic Liver Transplant Recipients: An Interim Analysis of a 3-Year Prospective, Observational Study"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":false,"given":"Milo","family":"Gatti","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna ,","place":["Italy"]},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna ,","place":["Italy"]},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Laici","sequence":"additional","affiliation":[{"name":"Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-1324","authenticated-orcid":false,"given":"Cecilia","family":"Bonazzetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna ,","place":["Italy"]},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Vizioli","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit for the treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Ambretti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna ,","place":["Italy"]},{"name":"Operative Unit of Microbiology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9742-1981","authenticated-orcid":false,"given":"Maria Cristina","family":"Morelli","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit for the treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Siniscalchi","sequence":"additional","affiliation":[{"name":"Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Giannella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna ,","place":["Italy"]},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna 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