A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis

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dc.contributor.authorDulhunty, J.
dc.contributor.authorRoberts, J.
dc.contributor.authorDavis, J.
dc.contributor.authorWebb, S.
dc.contributor.authorBellomo, R.
dc.contributor.authorGomersall, C.
dc.contributor.authorShirwadkar, C.
dc.contributor.authorEastwood, G.
dc.contributor.authorMyburgh, J.
dc.contributor.authorPaterson, D.
dc.contributor.authorStarr, T.
dc.contributor.authorPaul, S.
dc.contributor.authorLipman, J.
dc.contributor.authorPeck, L.
dc.contributor.authorYoung, H.
dc.contributor.authorBoschert, C.
dc.contributor.authorFletcher, J.
dc.contributor.authorSmith, J.
dc.contributor.authorNand, K.
dc.contributor.authorSara, T.
dc.contributor.authoret al.
dc.date.issued2015
dc.description.abstractRationale: Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing. Objectives: To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis. Methods: We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure–free days at Day 14, and duration of bacteremia. Measurements and Main Results: We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2–24) and 20 days (interquartile range, 3–24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63–1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77–1.63; P = 0.56). There was no difference in organ failure–free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24). Conclusions: In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion.
dc.description.statementofresponsibilityJoel M. Dulhunty, Jason A. Roberts, Joshua S. Davis, Steven A. R. Webb, Rinaldo Bellomo ... Milind Sanap ... et al.
dc.identifier.citationAmerican Journal of Respiratory and Critical Care Medicine, 2015; 192(11):1298-1305
dc.identifier.doi10.1164/rccm.201505-0857OC
dc.identifier.issn1073-449X
dc.identifier.issn1535-4970
dc.identifier.urihttp://hdl.handle.net/2440/113165
dc.language.isoen
dc.publisherATS Journals
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1013411
dc.rights© 2015 by the American Thoracic Society
dc.source.urihttps://doi.org/10.1164/rccm.201505-0857oc
dc.subjectBLING II Investigators for the ANZICS Clinical Trials Group *
dc.subjectHumans
dc.subjectSepsis
dc.subjectbeta-Lactams
dc.subjectAnti-Bacterial Agents
dc.subjectTreatment Outcome
dc.subjectLength of Stay
dc.subjectInfusions, Intravenous
dc.subjectDrug Administration Schedule
dc.subjectSurvival Analysis
dc.subjectProspective Studies
dc.subjectDouble-Blind Method
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.titleA multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis
dc.title.alternativeA multicenter randomized trial of continuous versus intermittent beta-lactam infusion in severe sepsis
dc.typeJournal article
pubs.publication-statusPublished

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