The DALI study: defining antibiotic levels in intensive care unit patients: prolonged infusion of beta-lactam antibiotics in critically ill patients

• Main Authors: Abdul Aziz, Mohd. Hafiz, Roberts, Jason A., Akova, Murat, Basetti, Matteo, De Waele, Jan, Dimopoulos, George, Kaukonen, Maija, Koulenti, Despoina, Martin, Claude, Montravers, Paul, Rello, Jordi, Rhodes, Alan, Starr, Therese, Wallis, Steven C., Lipman, Jeffrey
• Format: Conference or Workshop Item
• Language: English; English
• Published: 2013
• Subjects: RM Therapeutics. Pharmacology
• Online Access: http://irep.iium.edu.my/36784/4/the_DALI.pdf; http://irep.iium.edu.my/36784/7/ICAAC_2013_DALI_Poster_PI_v_IB_Finalv2.pdf; http://irep.iium.edu.my/36784/; http://www.icaaconline.com/php/icaac2013abstracts/start.htm
• Institution: Universiti Islam Antarabangsa Malaysia

Background – The aim of this study was to determine whether there is any pharmacokinetic and/or clinical advantage associated with the administration of beta-lactam antibiotics by prolonged infusion (PI; continuous or extended-infusion) compared to intermittent bolus (IB) dosing in critically ill patients. Methods - This report is part of the multi-national DALI study which included 68 intensive care units (ICU) throughout Europe. This study was a pharmacokinetic point-prevalence study, that was performed to describe concentrations of 3 beta-lactam antibiotics at two specified time-points. Differences in plasma antibiotic concentrations and clinical outcomes between PI and IB were assessed by using univariate and multivariate analyses. Results – This study included 224 critically ill patients whereby 63% and 37% of them received beta-lactam antibiotics via IB and PI dosing, respectively. IB dosing was preferred for piperacillin (IB 61% vs. PI 39%) and meropenem (IB 70% vs. PI 30%). The frequency of use of PI differed significantly between countries. PI demonstrated consistently higher drug concentrations compared to IB dosing. Clinical cure (IB 66% vs. PI 62%, p = 0.63), mortality (IB 28% vs. PI 30%, p = 0.87) and infection-related mortality rates (IB 22% vs. PI 17%, p = 0.288) were similar between PI and IB. Multiple regression analyses suggested that mortality was significantly predicted by SOFA score (OR = 1.10, 95% CI 1.00-1.21) and clinical cure (OR = 0.12, 95% CI 0.06-0.28). Only SOFA score predicted clinical cure (OR = 0.89, 95% CI 0.82-0.96). Conclusions – PI of beta-lactams is as effective as the traditional IB dosing in critically ill patients.