• Andrew A Udy, Joel M Dulhunty, Jason A Roberts, Joshua S Davis, Webb Steven A R SAR Department of Intensive Care, Royal Perth Hospital, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth,, Rinaldo Bellomo, Charles Gomersall, Charudatt Shirwadkar, Glenn M Eastwood, John Myburgh, David L Paterson, Therese Starr, Sanjoy K Paul, Jeffrey Lipman, BLING-II Investigators, and ANZICS Clinical Trials Group.
• Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Melbourne, VIC, Australia; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. Electronic address: a.udy@alfred.org.au.
• Int. J. Antimicrob. Agents. 2017 May 1; 49 (5): 624-630.

AbstractAugmented renal clearance (ARC) is known to influence β-lactam antibiotic pharmacokinetics. This substudy of the BLING-II trial aimed to explore the association between ARC and patient outcomes in a large randomised clinical trial. BLING-II enrolled 432 participants with severe sepsis randomised to receive β-lactam therapy by continuous or intermittent infusion. An 8-h creatinine clearance (CLCr) measured on Day 1 was used to identify ARC, defined as CLCr ≥ 130 mL/min. Patients receiving any form of renal replacement therapy were excluded. Primary outcome was alive ICU-free days at Day 28. Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation. A total of 254 patients were included, among which 45 (17.7%) manifested ARC [median (IQR) CLCr 165 (144-198) mL/min]. ARC patients were younger (P <0.001), more commonly male (P = 0.04) and had less organ dysfunction (P <0.001). There was no difference in ICU-free days at Day 28 [ARC, 21 (12-24) days; no ARC, 21 (11-25) days; P = 0.89], although clinical cure was significantly greater in the unadjusted analysis in those manifesting ARC [33/45 (73.3%) vs. 115/209 (55.0%) P = 0.02]. This was attenuated in the multivariable analysis. No difference was noted in 90-day mortality. There were no statistically significant differences in clinical outcomes in ARC patients according to the dosing strategy employed. In this substudy of a large clinical trial of β-lactam antibiotics in severe sepsis, ARC was not associated with any differences in outcomes, regardless of dosing strategy.Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

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