Association between augmented renal clearance and clinical outcomes in patients receiving b lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING II randomised, placebo controlled, clinical trial.
Augmented renal clearance (ARC) is known to influence b 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 b 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 b lactam antibiotics in severe sepsis, ARC was not associated with any differences in outcomes, regardless of dosing strategy.
International journal of antimicrobial agents