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

Udy, Andrew A., Dulhunty, Joel M., Roberts, Jason A., Davis, Joshua S., Webb, Steven A. R., Bellomo, Rinaldo, Gomersall, Charles, Shirwadkar, Charudatt, Eastwood, Glenn M., Myburgh, John, Paterson, David L., Starr, Therese, Paul, Sanjoy K. and Lipman, Jeffrey (2017) 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, 49 5: 624-630. doi:10.1016/j.ijantimicag.2016.12.022


Author Udy, Andrew A.
Dulhunty, Joel M.
Roberts, Jason A.
Davis, Joshua S.
Webb, Steven A. R.
Bellomo, Rinaldo
Gomersall, Charles
Shirwadkar, Charudatt
Eastwood, Glenn M.
Myburgh, John
Paterson, David L.
Starr, Therese
Paul, Sanjoy K.
Lipman, Jeffrey
Title 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
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 1872-7913
0924-8579
Publication date 2017-03-09
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2016.12.022
Open Access Status Not yet assessed
Volume 49
Issue 5
Start page 624
End page 630
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Subject 2726 Microbiology (medical)
2725 Infectious Diseases
2736 Pharmacology (medical)
Abstract Augmented renal clearance (ARC) is knownto influence beta-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 participantswith severe sepsis randomised to receive beta-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 patientswere 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 atDay 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 beta-lactam antibiotics in severe sepsis, ARC was not associated with any differences in outcomes, regardless of dosing strategy. (C)2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Formatted 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.
Keyword Augmented renal clearance
Critical illness
Sepsis
β-Lactams
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1048652
Institutional Status UQ

 
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