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

Int J Antimicrob Agents. 2017 May;49(5):624-630. doi: 10.1016/j.ijantimicag.2016.12.022. Epub 2017 Mar 9.

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.

Keywords: Augmented renal clearance; Critical illness; Sepsis; β-Lactams.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology
  • Cohort Studies
  • Creatinine / pharmacokinetics
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Metabolic Clearance Rate / physiology*
  • Middle Aged
  • Sepsis / drug therapy*
  • Sepsis / microbiology
  • Treatment Outcome
  • beta-Lactams / administration & dosage
  • beta-Lactams / pharmacokinetics*
  • beta-Lactams / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Creatinine