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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
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
Issue Date: 9-Mar-2017
EDate: 2017-03-09
Citation: 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
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Type: Journal Article
Subjects: Augmented renal clearance
Critical illness
Appears in Collections:Journal articles

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