Continuous versus intermittent β-lactam infusion in severe sepsis: a meta-analysis of individual patient data from randomized trials

Roberts, Jason A., Abdul-Aziz, Mohd-Hafiz, Davis, Joshua S., Dulhunty, Joel M., Cotta, Menino O., Myburgh, John, Bellomo, Rinaldo and Lipman, Jeffrey (2016) Continuous versus intermittent β-lactam infusion in severe sepsis: a meta-analysis of individual patient data from randomized trials. American Journal of Respiratory and Critical Care Medicine, 194 6: 681-691. doi:10.1164/rccm.201601-0024OC


Author Roberts, Jason A.
Abdul-Aziz, Mohd-Hafiz
Davis, Joshua S.
Dulhunty, Joel M.
Cotta, Menino O.
Myburgh, John
Bellomo, Rinaldo
Lipman, Jeffrey
Title Continuous versus intermittent β-lactam infusion in severe sepsis: a meta-analysis of individual patient data from randomized trials
Journal name American Journal of Respiratory and Critical Care Medicine   Check publisher's open access policy
ISSN 1073-449X
1535-4970
Publication date 2016-09-15
Sub-type Article (original research)
DOI 10.1164/rccm.201601-0024OC
Open Access Status Not yet assessed
Volume 194
Issue 6
Start page 681
End page 691
Total pages 11
Place of publication New York, NY, United States
Publisher American Thoracic Society
Collection year 2017
Language eng
Formatted abstract
Rationale: Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis.

Objectives: 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.

Methods: 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 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.

Measurements and Main Results: 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.

Conclusions: Compared with intermittent dosing, administration of β-lactamantibioticsby continuous infusionincritically ill patientswith severe sepsis is associated with decreased hospital mortality.
Keyword Antibiotic
Meropenem
Pharmacodynamics
Pharmacokinetics
Piperacillin-tazobactam
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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