Document Detail

Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial.
MedLine Citation:
PMID:  23074313     Owner:  NLM     Status:  MEDLINE    
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.
Joel M Dulhunty; Jason A Roberts; Joshua S Davis; Steven A R Webb; Rinaldo Bellomo; Charles Gomersall; Charudatt Shirwadkar; Glenn M Eastwood; John Myburgh; David L Paterson; Jeffrey Lipman
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-10-16
Journal Detail:
Title:  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America     Volume:  56     ISSN:  1537-6591     ISO Abbreviation:  Clin. Infect. Dis.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-20     Completed Date:  2013-06-10     Revised Date:  2013-08-16    
Medline Journal Info:
Nlm Unique ID:  9203213     Medline TA:  Clin Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  236-44     Citation Subset:  IM    
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, and Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane.
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MeSH Terms
Anti-Bacterial Agents / administration & dosage,  adverse effects,  pharmacokinetics,  therapeutic use*
Infusions, Intravenous
Middle Aged
Sepsis / drug therapy*,  microbiology,  mortality
Treatment Outcome
beta-Lactams / administration & dosage,  adverse effects,  pharmacokinetics,  therapeutic use*
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/beta-Lactams
Comment In:
Clin Infect Dis. 2013 Jul;57(2):323   [PMID:  23547168 ]
Clin Infect Dis. 2013 Jul;57(2):323-4   [PMID:  23547166 ]
Clin Infect Dis. 2013 Jan;56(2):245-7   [PMID:  23074312 ]

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