Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicentre double-blind, randomised controlled trial.

Dulhunty, Joel M., Roberts, Jason A., Webb, Joshua S., Webb, Steve A. R., Bellomo, Rinaldo, Gomersall, Charles, Shirwadkar, Charudatt, Eastwood, Glenn M., Myburgh, John, Paterson, David and Lipman, Jeffrey (2013) Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicentre double-blind, randomised controlled trial.. Clinical Infectious Diseases, 56 2: 236-244. doi:10.1093/cid/cis856


Author Dulhunty, Joel M.
Roberts, Jason A.
Webb, Joshua S.
Webb, Steve A. R.
Bellomo, Rinaldo
Gomersall, Charles
Shirwadkar, Charudatt
Eastwood, Glenn M.
Myburgh, John
Paterson, David
Lipman, Jeffrey
Title Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicentre double-blind, randomised controlled trial.
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1058-4838
1537-6591
Publication date 2013-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1093/cid/cis856
Open Access Status Not Open Access
Volume 56
Issue 2
Start page 236
End page 244
Total pages 9
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Subject 2726 Microbiology (medical)
2725 Infectious Diseases
Abstract This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis.
Formatted abstract
Background: Beta-lactam antibiotics are a commonly used treatment for severe sepsis, with intermittent bolus dosing standard therapy, despite a strong theoretical rationale for continuous administration. The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis.

Methods: This was a prospective, double-blind, randomized controlled trial of continuous infusion versus intermittent bolus dosing of piperacillin-tazobactam, meropenem, and ticarcillin-clavulanate conducted in 5 intensive care units across Australia and Hong Kong. The primary pharmacokinetic outcome on treatment analysis was plasma antibiotic concentration above the minimum inhibitory concentration (MIC) on days 3 and 4. The assessed clinical outcomes were clinical response 7-14 days after study drug cessation, ICU-free days at day 28 and hospital survival.

Results: Sixty patients were enrolled with 30 patients each allocated to the intervention and control groups. Plasma antibiotic concentrations exceeded the MIC in 82% of patients (18 of 22) in the continuous arm versus 29% (6 of 21) in the intermittent arm (P =. 001). Clinical cure was higher in the continuous group (70% vs 43%; P =. 037), but ICU-free days (19.5 vs 17 days; P =. 14) did not significantly differ between groups. Survival to hospital discharge was 90% in the continuous group versus 80% in the intermittent group (P =. 47).

Conclusions:
Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure. This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints.
Keyword Clinical outcome
Meropenem
Pharmacokinetics
Piperacillin-tazobactam
Ticarcillin-clavulanate
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 569917
Institutional Status UQ
Additional Notes First published online: 16 October 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
 
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Created: Thu, 06 Dec 2012, 02:53:31 EST by Sia Athanasas on behalf of Anaesthesiology and Critical Care - RBWH