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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Continuous infusion of beta-lactam antibiotics in severe sepsis: A multicenter double-blind, randomized controlled trial
Clinical Infectious Diseases, Volume 56, No. 2, Year 2013
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Description
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. © 2012 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Dulhunty, Joel M.
Australia, Brisbane
Royal Brisbane and Women's Hospital
Roberts, Jason A.
Australia, Brisbane
Royal Brisbane and Women's Hospital
Davis, Joshua S.
Australia, Darwin
Charles Darwin University
Webb, Steve A.R.
Australia, Perth
The University of Western Australia
Bellomo, Rinaldo
Australia, Melbourne
Austin Hospital
Gomersall, Charles David
Hong Kong, Hong Kong
Chinese University of Hong Kong
Eastwood, Glenn
Australia, Melbourne
Austin Hospital
Myburgh, John A.
Australia, Sydney
George Institute for Global Health
Paterson, David L.
Australia, Brisbane
Royal Brisbane and Women's Hospital
Lipman, Jeffrey
Australia, Brisbane
Royal Brisbane and Women's Hospital
Statistics
Citations: 288
Authors: 10
Affiliations: 7
Identifiers
Doi:
10.1093/cid/cis856
ISSN:
15376591
Research Areas
Disability
Health System And Policy
Study Design
Randomised Control Trial
Cohort Study
Study Approach
Quantitative