Chest
Volume 136, Issue 5, November 2009, Pages 1237-1248
Journal home page for Chest

Original Research
Critical Care Medicine
Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock

https://doi.org/10.1378/chest.09-0087Get rights and content

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.

Section snippets

Materials and Methods

A retrospective review of adult patients (ā‰„ 18 years of age) who had received a diagnosis of septic shock was performed. A waived consent protocol was approved by the health ethics boards of the University of Manitoba and at each individual participating center. Consecutive adult patients with septic shock from 22 medical institutions from Canada (17 sites), the United States (4 sites), and Saudi Arabia (1 site) were collected from discrete periods between 1996 and 2005. Each institution

Demographic and Descriptive Data

In total, 5,715 cases were found to fit the diagnostic criteria for septic shock. The mean age of case patients with septic shock was 62.6 Ā± 16.3 years, with 56.3% male patients and 43.7% female patients. The mean acute physiology and chronic health evaluation (APACHE) II score32 determined from the most abnormal results within 24 h of shock onset was 25.2 Ā± 9.7. Treatment with drotrecogin-alfa (activated)33 was used in 124 cases (outside of randomized trials), while low-dose steroid therapy

Discussion

These data suggest that the provision of inappropriate initial empiric antimicrobial therapy has a very substantial adverse effect on survival in patients with septic shock and that this effect is present across all major clinical subgroups. Further, the study confirms that the occurrence of the initiation of organism-inappropriate empiric therapy is surprisingly common.

The degree to which the administration of inappropriate initial empiric therapy adversely affected survival in the study group

Acknowledgments

Author contributions: Study design: Dr. Anand Kumar. Data collection: members of the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Data analysis and interpretation: Drs. Anand Kumar and Chateau. Manuscript development: Drs. Anand Kumar, Ellis, Arabi, Roberts, Light, Parrillo, Dodek, Wood, Aseem Kumar, Ahsan, and Simon, and Ms. Peters. Dr. Anand Kumar had full access to all of the data in the study, and takes responsibility for the integrity of the data and the

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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).

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A complete list of participants is located in Appendix 3.

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