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Using the Number Needed to Treat to Assess Appropriate Antimicrobial Therapy as a Determinant of Outcome in Severe Sepsis and Septic Shock*

Vazquez-Guillamet, Cristina MD; Scolari, Michael; Zilberberg, Marya D. MD; Shorr, Andrew F. MD, MPH; Micek, Scott T. PharmD; Kollef, Marin MD

doi: 10.1097/CCM.0000000000000516
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Objective: To assess appropriate antimicrobial therapy as an outcome determinant in severe sepsis and septic shock using the number needed to treat.

Design: Single-center cohort study (January 2008 to December 2012).

Setting: One thousand two hundred fifty-bed academic hospital.

Patients: Two thousand five hundred ninety-four patients with positive blood culture.

Interventions: We retrospectively identified patients with severe sepsis or septic shock. Inappropriate antimicrobial treatment was defined as an antimicrobial regimen that lacked in vitro activity against the isolated pathogen. Information regarding demographics, severity of illness, comorbidities, microbiology, and antimicrobial treatment was recorded. Logistic regression was used to identify risk factors for hospital mortality and inappropriate treatment.

Measurements and Main Results: Seven hundred eighty-seven patients (30.3%) were nonsurvivors. Inappropriate antimicrobial treatment had the greatest adjusted odds ratio for hospital mortality (adjusted odds ratio, 3.4; 95% CI, 2.8–4.1; p < 0.001). Multivariate logistic regression analysis identified resistance to cefepime, resistance to meropenem, presence of multidrug resistance, nonabdominal surgery, and prior antibiotic use as being independently associated with the administration of inappropriate antimicrobial treatment. For the entire cohort, the number needed to treat with appropriate antimicrobial therapy to prevent one patient death was 4.0 (95% CI, 3.7–4.3). The prevalence-adjusted pathogen-specific number needed to treat (PNNT) with appropriate antimicrobial therapy to prevent one patient death was lowest for multidrug-resistant bacteria (PNNT = 20) followed by Candida species (PNNT = 34), methicillin-resistant Staphylococcus aureus (PNNT = 38), Pseudomonas aeruginosa (PNNT = 38), Escherichia coli (PNNT = 40), and methicillin-susceptible S. aureus (PNNT = 47).

Conclusions: Our results support the importance of appropriate antimicrobial treatment as a determinant of outcome in patients with severe sepsis and septic shock. Our analyses suggest that improved targeting of empiric antimicrobials for multidrug-resistant bacteria, Candida species, methicillin-resistant S. aureus, and P. aeruginosa would have the greatest impact in reducing mortality from inappropriate antimicrobial treatment in patients with severe sepsis and septic shock.

1Division of Infectious Diseases, University of New Mexico, Albuquerque, NM.

2Pulmonary and Critical Care Division, Washington University School of Medicine, St. Louis, MO.

3School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA.

4Pulmonary and Critical Care Division, Washington Hospital Center, Washington, D.C.

5Division of Pharmacy Practice, St. Louis College of Pharmacy, St. Louis, MO.

* See also p. 2444.

This work was performed at Barnes-Jewish Hospital, St. Louis, MO.

Dr. Vazquez-Guillamet had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of the data analysis, and contributed to the study conception and design, statistical analysis, and critical revision of the manuscript. Mr. Scolari assisted in the data acquisition, database development, and critical revision of the manuscript. Drs. Zilberberg, Shorr, Micek, and Kollef had full access to all of the data in the study, take responsibility for the integrity of the data and the accuracy of the data analysis, and contributed to the study conception and design, statistical analysis, and critical revision of the manuscript.

Supported, in part, by an unrestricted grant from the Cubist Pharmaceuticals.

Dr. Shorr has been a consultant to, served as a speaker for, or received grant support from Astrazeneca, Astellas, Bayer, Cubist, Forest, and Pfizer. Dr. Kollef and his institution received grant support from the Barnes-Jewish Hospital Foundation. His institution received grant support from the Cubist Pharmaceuticals (work supported in part by unrestricted grant from Cubist). The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: mkollef@dom.wustl.edu

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