Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: Data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study

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• 作者：Mahipal G Sinnollareddy (1) (2) (3)
  Jason A Roberts (1) (4)
  Jeffrey Lipman (1) (4)
  Murat Akova (5)
  Matteo Bassetti (6)
  Jan J De Waele (7)
  Kirsi-Maija Kaukonen (8)
  Despoina Koulenti (1) (9)
  Claude Martin (10) (11)
  Philippe Montravers (12)
  Jordi Rello (13)
  Andrew Rhodes (14)
  Therese Starr (4)
  Steven C Wallis (1)
  George Dimopoulos (9)
  on behalf of the DALI Study authors
  
  1. Burns Trauma and Critical Care Research Centre ; The University of Queensland ; Brisbane ; Australia
  2. School of Pharmacy and Medical Sciences ; University of South Australia ; Adelaide ; Australia
  3. Therapeutics Research Centre ; Basil Hetzel Institute for Translational Health Research ; The Queen Elizabeth Hospital ; Adelaide ; Australia
  4. Royal Brisbane and Women鈥檚 Hospital ; Brisbane ; Australia
  5. School of Medicine ; Hacettepe University ; Ankara ; Turkey
  6. Azienda Ospedaliera Universitaria Santa Maria della Misericordia ; Udine ; Italy
  7. Ghent University Hospital ; Ghent ; Belgium
  8. Helsinki University Central Hospital ; Helsinki ; Finland
  9. Attikon University Hospital ; Athens ; Greece
  10. Hospital Nord ; Marseille ; France
  11. AzuRea Group ; Antibes ; France
  12. Centre Hospitalier Universitaire Bichat-Claude Bernard ; AP-HP ; Universit茅 Paris VII ; Paris ; France
  13. CIBERES ; Vall d鈥橦ebron Institute of Research ; Universitat Autonoma de Barcelona ; Barcelona ; Spain
  14. St George鈥檚 Healthcare NHS Trust and St George鈥檚 University of London ; London ; England
  
• 刊名：Critical Care
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：19
• 期：1
• 全文大小：474 KB
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• 刊物主题：Intensive / Critical Care Medicine; Emergency Medicine;
• 出版者：BioMed Central
• ISSN：1364-8535

文摘

Introduction The objective of the study was to describe the pharmacokinetics (PK) of fluconazole, anidulafungin, and caspofungin in critically ill patients and to compare with previously published data. We also sought to determine whether contemporary fluconazole doses achieved PK/pharmacodynamic (PD; PK/PD) targets in this cohort of intensive care unit patients. Methods The Defining Antibiotic Levels in Intensive care unit patients (DALI) study was a prospective, multicenter point-prevalence PK study. Sixty-eight intensive care units across Europe participated. Inclusion criteria were met by critically ill patients administered fluconazole (n鈥?鈥?5), anidulafungin (n鈥?鈥?), and caspofungin (n鈥?鈥?). Three blood samples (peak, mid-dose, and trough) were collected for PK/PD analysis. PK analysis was performed by using a noncompartmental approach. Results The mean age, weight, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores of the included patients were 58聽years, 84聽kg, and 22, respectively. Fluconazole, caspofungin, and anidulafungin showed large interindividual variability in this study. In patients receiving fluconazole, 33% did not attain the PK/PD target, ratio of free drug area under the concentration-time curve from 0 to 24聽hours to minimum inhibitory concentration (fAUC0鈥?4/MIC) 鈮?00. The fluconazole dose, described in milligrams per kilogram, was found to be significantly associated with achievement of fAUC0鈥?4/MIC 鈮?00 (P鈥?鈥?.0003). Conclusions Considerable interindividual variability was observed for fluconazole, anidulafungin, and caspofungin. A large proportion of the patients (33%) receiving fluconazole did not attain the PK/PD target, which might be related to inadequate dosing. For anidulafungin and caspofungin, dose optimization also appears necessary to minimize variability.