02583nas a2200301   4500000000100000008004100001100003300042700002000075700001400095700001600109700001900125700001600144700001500160700001800175700001800193700001700211700002200228700002500250700001900275700001900294700001800313700002700331245024900358300001200607490000700619520164100626022001402267       2017                            d1 aANZICS Clinical Trials Group1 aBellomo Rinaldo1 aMyburgh J1 aWebb Steven1 aLipman Jeffrey1 aPaul Sanjoy1 aUdy Andrew1 aDulhunty Joel1 aRoberts Jason1 aDavis Joshua1 aGomersall Charles1 aShirwadkar Charudatt1 aEastwood Glenn1 aPaterson David1 aStarr Therese1 aBLING-II Investigators00aAssociation 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.  a624-6300 v493 a<p>
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 &lt;0.001), more commonly male (P = 0.04) and had less organ dysfunction (P &lt;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.
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