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
File version
Author(s)
Dulhunty, Joel M
Roberts, Jason A
Davis, Joshua S
Webb, Steven AR
Bellomo, Rinaldo
Gomersall, Charles
Shirwadkar, Charudatt
Eastwood, Glenn M
Myburgh, John
Paterson, David L
Starr, Therese
Paul, Sanjoy K
Heffernan, Aaron J
et al.
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
License
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.
Journal Title
International Journal of Antimicrobial Agents
Conference Title
Book Title
Edition
Volume
49
Issue
5
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Medical microbiology
Pharmacology and pharmaceutical sciences
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Microbiology
Pharmacology & Pharmacy
Persistent link to this record
Citation
Udy, AA; Dulhunty, JM; Roberts, JA; Davis, JS; Webb, SAR; Bellomo, R; Gomersall, C; Shirwadkar, C; Eastwood, GM; Myburgh, J; Paterson, DL; Starr, T; Paul, SK; Heffernan, AJ; et al., 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, International Journal of Antimicrobial Agents, 2017, 49 (5), pp. 624-630