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Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock From the First Hour

Results From a Guideline-Based Performance Improvement Program*

Ferrer, Ricard MD, PhD1; Martin-Loeches, Ignacio MD, PhD2; Phillips, Gary MAS3; Osborn, Tiffany M. MD, MPH4; Townsend, Sean MD5; Dellinger, R. Phillip MD, FCCP, FCCM6; Artigas, Antonio MD, PhD2; Schorr, Christa RN, MSN6; Levy, Mitchell M. MD, FCCP, FCCM7

doi: 10.1097/CCM.0000000000000330
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Objectives: Compelling evidence has shown that aggressive resuscitation bundles, adequate source control, appropriate antibiotic therapy, and organ support are cornerstone for the success in the treatment of patients with sepsis. Delay in the initiation of appropriate antibiotic therapy has been recognized as a risk factor for mortality. To perform a retrospective analysis on the Surviving Sepsis Campaign database to evaluate the relationship between timing of antibiotic administration and mortality.

Design: Retrospective analysis of a large dataset collected prospectively for the Surviving Sepsis Campaign.

Setting: One hundred sixty-five ICUs in Europe, the United States, and South America.

Patients: A total of 28,150 patients with severe sepsis and septic shock, from January 2005 through February 2010, were evaluated.

Interventions: Antibiotic administration and hospital mortality.

Measurements and Main Results: A total of 17,990 patients received antibiotics after sepsis identification and were included in the analysis. In-hospital mortality was 29.7% for the cohort as a whole. There was a statically significant increase in the probability of death associated with the number of hours of delay for first antibiotic administration. Hospital mortality adjusted for severity (sepsis severity score), ICU admission source (emergency department, ward, vs ICU), and geographic region increased steadily after 1 hour of time to antibiotic administration. Results were similar in patients with severe sepsis and septic shock, regardless of the number of organ failure.

Conclusions: The results of the analysis of this large population of patients with severe sepsis and septic shock demonstrate that delay in first antibiotic administration was associated with increased in-hospital mortality. In addition, there was a linear increase in the risk of mortality for each hour delay in antibiotic administration. These results underscore the importance of early identification and treatment of septic patients in the hospital setting.

1Department of Intensive Care, Mútua Terrassa University Hospital, CIBER Enfermedades Respiratorias, Barcelona, Spain.

2Critical Care Center, Sabadell Hospital, CIBER Enfermedades Respiratorias, Corporacion Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Spain.

3The Ohio State University Center for Biostatistics, Columbus, OH.

4Department of Surgery and Emergency Medicine, Division of Acute Care Surgery, Surgical/Trauma Critical Care, Barnes Jewish Hospital, Washington University, St. Louis, MO.

5California Pacific Medical Center, San Francisco, CA.

6Brown University/Rhode Island Hospital, Providence, RI.

7Cooper University Hospital, Camden, NJ.

* See also p. 1931.

Dr. Levy had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Initial funding for the Surviving Sepsis Campaign (from 2002 to 2006) was through unrestricted educational grants from Eli Lilly, Edwards Lifesciences, Phillips Medical Systems, and the Coalition for Critical Care Excellence (Society of Critical Care Medicine). There was no involvement by the sponsors in the development, data analysis, or manuscript preparation of the current study. No additional funding has been received since that time or during the analysis and development of the current study and manuscript.

Dr. Ferrer served as board member for Laboratorios Ferrer and lectured for Merck, Sharp and Dohme, and Pfizer. His institution received grant support from Instituto de Salud Carlos III. Mr. Phillips received support for participation in review activities from the Rhode Island Hospital, a Lifespan Partner. His institution received grant support from the National Institutes of Health Grant and Murdoch Children’s Research Institution. Dr. Osborn consulted for Institute of Healthcare Improvement (sepsis consultant on quality initiative); and received support for travel from American College of Emergency Physicians (Scientific Assembly 2011, 2012, 2013. Dr. Townsend received support for article research from the Gordon and Betty Moore Foundation. Dr. Dellinger received support for travel for the meeting of Surviving Sepsis Campaign (SSC) steering committee. Dr. Artigas served as board member for Ferrer Farma, consulted for Hill Rom, and lectured for Pulsion. His institution received grant support from Pulsion. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins