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Clinical question: Does the appropriateness of the initial empiric antimicrobial agents started at the onset of septic shock have an impact on outcomes in this clinical syndrome?

Background: Septic shock is a common cause of death among ICU patients. Prompt initiation of appropriate antimicrobial therapy is key to improving outcomes. This study evaluates the effects of initiating inappropriate empiric antimicrobial therapy.

Study design: Retrospective cohort study.

Setting: Twenty-two hospitals in the U.S., Canada, and Saudi Arabia.

Synopsis: Records of more than 5,700 patients with septic shock were reviewed. Appropriate antimicrobial therapy was defined as agents with in vitro activity for the isolated microorganism(s), or if the antimicrobial agents provided adequate empiric coverage for local community and nosocomial flora in culture-negative shock. The main outcome variable was survival to hospital discharge.

The overall survival-to-hospital discharge was 43.7%, and 80.1% of patients received appropriate empiric antimicrobial therapy. Of those who died, 4.8% did not receive appropriate therapy. Inappropriate antimicrobial regimens caused survival to fall to 10.3% from 52.0% (OR 9.45; 95% CI, 7.74 to 11.54; p<0.0001).

After adjusting for potential confounding variables, the inappropriateness of initial antimicrobial therapy remained strongly associated with risk of death (OR 8.99; 95% CI, 6.60 to 12.23; p<0.0001).

The primary weakness of the study is that it was observational.

Bottom line: The choice of an appropriate empiric antimicrobial agent is a critical determinant of survival in patients with septic shock.

Citation: Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136(5):1237-1248.

Reviewed for TH eWire by Sameer Badlani, MD, Stacy S. Banerjee, MD, Alan J. Jung, MD, Elizabeth Marlow, MD, MPP, Valerie G. Press, MD, MPH, Milda R. Saunders, MD, MPH, Nilam J. Soni, MD, Srilaxmi Tumuluri, MD, Section of Hospital Medicine, University of Chicago

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