{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:14:20Z","timestamp":1791126860370,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Emerging data suggest that more aggressive beta-lactam PK\/PD targets could minimize the occurrence of microbiological failure and\/or resistance development. This study aims to assess whether a PK\/PD target threshold of continuous infusion (CI) beta-lactams may be useful in preventing microbiological failure and\/or resistance development in critically ill patients affected by documented Gram-negative infections. Methods: Patients admitted to intensive care units from December 2020 to July 2021 receiving continuous infusion beta-lactams for documented Gram-negative infections and having at least one therapeutic drug monitoring in the first 72 h of treatment were included. A receiver operating characteristic (ROC) curve analysis was performed using the ratio between steady-state concentration and minimum inhibitory concentration (Css\/MIC) ratio as the test variable and occurrence of microbiological failure as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. Independent risk factors for the occurrence of microbiological failure were investigated using logistic regression. Results: Overall, 116 patients were included. Microbiological failure occurred in 26 cases (22.4%). A Css\/MIC ratio \u2264 5 was identified as PK\/PD target cut-off with sensitivity of 80.8% (CI 60.6\u201393.4%) and specificity of 90.5% (CI 74.2\u201394.4%), and with an AUC of 0.868 (95%CI 0.793\u20130.924; p &lt; 0.001). At multivariate regression, independent predictors of microbiological failure were Css\/MIC ratio \u2264 5 (odds ratio [OR] 34.54; 95%CI 7.45\u2013160.11; p &lt; 0.001) and Pseudomonas aeruginosa infection (OR 4.79; 95%CI 1.11\u201320.79; p = 0.036). Conclusions: Early targeting of CI beta-lactams at Css\/MIC ratio &gt; 5 during the treatment of documented Gram-negative infections may be helpful in preventing microbiological failure and\/or resistance development in critically ill patients.<\/jats:p>","DOI":"10.3390\/antibiotics10111311","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T22:00:23Z","timestamp":1635372023000},"page":"1311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Assessment of a PK\/PD Target of Continuous Infusion Beta-Lactams Useful for Preventing Microbiological Failure and\/or Resistance Development in Critically Ill Patients Affected by Documented Gram-Negative Infections"],"prefix":"10.3390","volume":"10","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, 40138 Bologna, Italy"},{"name":"SSD Clinical Pharmacology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Giorgio","family":"Cojutti","sequence":"additional","affiliation":[{"name":"SSD Clinical Pharmacology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Pascale","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-3595","authenticated-orcid":false,"given":"Tommaso","family":"Tonetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Division of Anesthesia and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-6323","authenticated-orcid":false,"given":"Cristiana","family":"Laici","sequence":"additional","affiliation":[{"name":"Division of Anesthesiology, Department of Anesthesia and Intensive Care of Abdominal Organ Transplantation and Hepatobiliary Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Dell\u2019Olio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Division of Anesthesia and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Siniscalchi","sequence":"additional","affiliation":[{"name":"Division of Anesthesiology, Department of Anesthesia and Intensive Care of Abdominal Organ Transplantation and Hepatobiliary Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, 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, 40138 Bologna, Italy"},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-7167","authenticated-orcid":false,"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"SSD Clinical Pharmacology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1001\/jama.2016.11764","article-title":"Antimicrobial Resistance","volume":"316","author":"Marston","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/s13054-018-2155-1","article-title":"Pharmacokinetics-Pharmacodynamics Issues Relevant for the Clinical Use of Beta-Lactam Antibiotics in Critically Ill Patients","volume":"22","author":"Veiga","year":"2018","journal-title":"Crit. 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