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Title: Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial
Austin Authors: Udy, Andrew A;Dulhunty, Joel M;Roberts, Jason A;Davis, Joshua S;Webb, Steven A;Bellomo, Rinaldo ;Gomersall, Charles;Shirwadkar, Charudatt;Eastwood, Glenn M ;Myburgh, John;Paterson, David L;Starr, Therese;Paul, Sanjoy K;Lipman, Jeffrey;BLING-II Investigators;ANZICS Clinical Trials Group
Affiliation: Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Melbourne, Victoria, Australia
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
Burns, Trauma & Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia
Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia
Department of Intensive Care, Royal Perth Hospital, Perth, WA, Australia
School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Prince of Wales Hospital, Hong Kong SAR
Chinese University of Hong Kong, Hong Kong SAR
Department of Intensive Care, Blacktown Hospital, Blacktown, NSW, Australia
Critical Care and Trauma Division, The George Institute for Global Health, Sydney, NSW, Australia
St George Clinical School, University of New South Wales, Sydney, NSW, Australia
Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia
Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
Issue Date: 9-Mar-2017
Date: 2017-03-09
Publication information: International Journal of Antimicrobial Agents 2017; online first: 9 March
Abstract: Augmented 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.
DOI: 10.1016/j.ijantimicag.2016.12.022
ORCID: 0000-0002-1650-8939
Journal: International Journal of Antimicrobial Agents
PubMed URL:
Type: Journal Article
Subjects: Augmented renal clearance
Critical illness
Appears in Collections:Journal articles

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