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Original Research: CRITICAL CARE MEDICINE |

Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock

Anand Kumar, MD; Paul Ellis, MD; Yaseen Arabi, MD, FCCP; Dan Roberts, MD; Bruce Light, MD; Joseph E. Parrillo, MD, FCCP; Peter Dodek, MD; Gordon Wood, MD; Aseem Kumar, PhD; David Simon, MD; Cheryl Peters, RN; Muhammad Ahsan, MD; Dan Chateau, PhD; the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group
Author and Funding Information

Affiliations: From the Section of Critical Care Medicine (Dr. Anand Kumar, Roberts, Light, and Ahsan, and Ms. Peters), Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada; the Department of Emergency Medicine (Dr. Ellis), University Health Network, University of Toronto, Toronto, ON, Canada; Intensive Care Department (Dr. Arabi), King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; Cooper Hospital/University Medical Center (Drs. Anand Kumar and Parrillo), Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden; the Section of Critical Care Medicine (Dr. Dodek), St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada; Critical Care Medicine (Dr. Wood), Royal Jubilee and Victoria General Hospitals, Vancouver Island Health Authority, Victoria, BC, Canada; Biomolecular Sciences Program and Department of Chemistry and Biochemistry (Dr. Aseem Kumar), Laurentian University, Sudbury, ON, Canada; the Section of Infectious Diseases (Dr. Simon), Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL; and the Biostatistical Consulting Unit (Dr. Chateau), Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Correspondence to: Anand Kumar, MD, Section of Critical Care Medicine, Health Sciences Centre, JJ 399, University of Manitoba, 700 William Ave, Winnipeg, MB, Canada R3E-0Z3; e-mail: akumar61@yahoo.com

*A complete list of participants is located in Appendix 3.


Funding/Support: Astellas Pharma Inc, Eli-Lilly and Co, Pfizer Inc, Bayer Inc, Merck and Co, Wyeth Pharmaceuticals, Bristol-Myers Squibb Co, and Astra-Zeneca, Inc, provided unrestricted grants in support of this study. Additional support was provided by the Health Sciences Centre Department of Research and Health Sciences Centre Foundation.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(5):1237-1248. doi:10.1378/chest.09-0087
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Objective:  Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock.

Methods:  The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries.

Results:  Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23).

Conclusions:  Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.

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