Gennaro De Pascale, Lucia Lisi, Salvatore Lucio Cutuli, Carlotta Marinozzi, Altea Palladini, Elena Sancho Ferrando, Eloisa Sofia Tanzarella, Gianmarco Lombardi, Domenico Luca Grieco, Alessandro Caroli, Rikardo Xhemalaj, Laura Cascarano, Gabriella Maria Pia Ciotti, Claudio Sandroni, Maurizio Sanguinetti, Pierluigi Navarra, Massimo Antonelli
{"title":"接受持续肾脏替代疗法的重症患者的大剂量可乐定药物动力学。","authors":"Gennaro De Pascale, Lucia Lisi, Salvatore Lucio Cutuli, Carlotta Marinozzi, Altea Palladini, Elena Sancho Ferrando, Eloisa Sofia Tanzarella, Gianmarco Lombardi, Domenico Luca Grieco, Alessandro Caroli, Rikardo Xhemalaj, Laura Cascarano, Gabriella Maria Pia Ciotti, Claudio Sandroni, Maurizio Sanguinetti, Pierluigi Navarra, Massimo Antonelli","doi":"10.1186/s13613-024-01384-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT.</p><p><strong>Results: </strong>All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5-59.3] and 9 [6.7-11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8-20.6] and 3.9 mcg/mL [3.3-4.4], respectively. Median area under the time-concentration curve (AUC<sub>0 - 24</sub>) and average steady-state concentration (C<sub>ss, avg</sub>) were 193.9 mcg h/mL [170.6-208.6] and 8.07 mcg/mL [7.1-8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC<sub>0 - 24</sub>/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of C<sub>ss, avg</sub> 3-4 mcg/mL.</p><p><strong>Conclusions: </strong>In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC<sub>90</sub>, but exceeding the safety C<sub>ss, avg</sub>. limit.</p><p><strong>Trial registration: </strong>This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133).</p>","PeriodicalId":7966,"journal":{"name":"Annals of Intensive Care","volume":"14 1","pages":"152"},"PeriodicalIF":5.7000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438743/pdf/","citationCount":"0","resultStr":"{\"title\":\"High-dose colistin pharmacokinetics in critically ill patients receiving continuous renal replacement therapy.\",\"authors\":\"Gennaro De Pascale, Lucia Lisi, Salvatore Lucio Cutuli, Carlotta Marinozzi, Altea Palladini, Elena Sancho Ferrando, Eloisa Sofia Tanzarella, Gianmarco Lombardi, Domenico Luca Grieco, Alessandro Caroli, Rikardo Xhemalaj, Laura Cascarano, Gabriella Maria Pia Ciotti, Claudio Sandroni, Maurizio Sanguinetti, Pierluigi Navarra, Massimo Antonelli\",\"doi\":\"10.1186/s13613-024-01384-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT.</p><p><strong>Results: </strong>All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5-59.3] and 9 [6.7-11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8-20.6] and 3.9 mcg/mL [3.3-4.4], respectively. Median area under the time-concentration curve (AUC<sub>0 - 24</sub>) and average steady-state concentration (C<sub>ss, avg</sub>) were 193.9 mcg h/mL [170.6-208.6] and 8.07 mcg/mL [7.1-8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC<sub>0 - 24</sub>/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of C<sub>ss, avg</sub> 3-4 mcg/mL.</p><p><strong>Conclusions: </strong>In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC<sub>90</sub>, but exceeding the safety C<sub>ss, avg</sub>. limit.</p><p><strong>Trial registration: </strong>This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133).</p>\",\"PeriodicalId\":7966,\"journal\":{\"name\":\"Annals of Intensive Care\",\"volume\":\"14 1\",\"pages\":\"152\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-09-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438743/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Intensive Care\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13613-024-01384-1\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Intensive Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13613-024-01384-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Background: Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT.
Results: All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5-59.3] and 9 [6.7-11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8-20.6] and 3.9 mcg/mL [3.3-4.4], respectively. Median area under the time-concentration curve (AUC0 - 24) and average steady-state concentration (Css, avg) were 193.9 mcg h/mL [170.6-208.6] and 8.07 mcg/mL [7.1-8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC0 - 24/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of Css, avg 3-4 mcg/mL.
Conclusions: In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC90, but exceeding the safety Css, avg. limit.
Trial registration: This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133).
期刊介绍：
Annals of Intensive Care is an online peer-reviewed journal that publishes high-quality review articles and original research papers in the field of intensive care medicine. It targets critical care providers including attending physicians, fellows, residents, nurses, and physiotherapists, who aim to enhance their knowledge and provide optimal care for their patients. The journal's articles are included in various prestigious databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, OCLC, PubMed, PubMed Central, Science Citation Index Expanded, SCOPUS, and Summon by Serial Solutions.
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