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.