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Title: Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials.
Austin Authors: Roberts, Jason A;Abdul-Aziz, Mohd-Hafiz;Davis, Joshua S;Dulhunty, Joel M;Cotta, Menino O;Myburgh, John;Bellomo, Rinaldo ;Lipman, Jeffrey
Affiliation: Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia
Department of Intensive Care, Austin Hospital, Melbourne, Australia
St. George Clinical School, University of New South Wales, Sydney, Australia
School of Pharmacy, The University of Queensland, Brisbane, Australia
School of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia
Department of Infectious Diseases, John Hunter Hospital, Newcastle, Australia
Redcliffe Hospital, Brisbane, Australia
Critical Care and Trauma Division, The George Institute for Global Health, Sydney, Australia
Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia
Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
Burns, Trauma & Critical Care Research Centre, Royal Brisbane and Women's Hospital, Brisbane, Australia
Menzies School of Health Research, Charles Darwin University, Darwin, Australia
Issue Date: 15-Sep-2016
Publication information: American Journal of Respiratory and Critical Care Medicine 2016; 194(6): 681-91
Abstract: Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis. In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics. We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 3days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis. We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure. Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
DOI: 10.1164/rccm.201601-0024OC
ORCID: 0000-0002-1650-8939
Journal: American Journal of Respiratory and Critical Care Medicine
PubMed URL: 26974879
Type: Journal Article
Subjects: antibiotic
Appears in Collections:Journal articles

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