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Published on: June 15, 2019
Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating
Stephan Harbarth1, Jorge Garbino, Jérome Pugin
1Divisions of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland. harbarth@post.harvard.edu
Purpose:
To examine the effect of inappropriate initial antimicrobial therapy on the prognosis of patients with sepsis who were enrolled in a clinical trial of an immunomodulating agent conducted in 108 hospitals in North America and Europe.
Methods:
We assessed initial antimicrobial choice and results of microbiologic cultures in 904 patients who had microbiologically confirmed severe sepsis or early septic shock. If a patient did not receive at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 hours from the diagnosis of severe sepsis, then the initial antimicrobial treatment was considered to be inappropriate. A propensity score that adjusted for factors associated with inappropriate antimicrobial treatment was calculated and included in multivariable models to adjust for confounding.
Results:
A total of 468 patients (52%) had documented bloodstream infection, and 211 patients (23%) received inappropriate initial antimicrobial therapy. Characteristics associated with inappropriate treatment were study enrollment in Europe, admission to surgery, nosocomial infection, infection with multiresistant microorganisms, and fungal or polymicrobial infection (all P <0.05). The 28-day mortality was 24% (168/693) for patients in the adequately treated group versus 39% (82/211) for patients receiving inappropriate initial antimicrobial therapy (P <0.001). After adjusting for comorbid conditions, severity of illness, site of infection, and the propensity score, inappropriate antimicrobial therapy was independently associated with increased mortality (odds ratio = 1.8; 95% confidence interval: 1.2 to 2.6).
Conclusion:
In a large cohort of patients with microbiologically confirmed severe sepsis, appropriate initial antimicrobial therapy was an important determinant of survival. New approaches aimed at improving detection and treatment of early sepsis are needed.
Insights
Appropriate initial antimicrobial therapy significantly improves survival in severe sepsis patients. Inappropriate treatment increases mortality risk, highlighting the need for better early detection and management strategies.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Critical Care Medicine
Background:
- Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
- Initial antimicrobial therapy is crucial for sepsis patient outcomes.
- The impact of inappropriate initial antimicrobial treatment on sepsis prognosis requires further investigation.
Purpose of the Study:
- To evaluate the association between inappropriate initial antimicrobial therapy and prognosis in severe sepsis patients.
- To identify factors associated with inappropriate antimicrobial treatment in sepsis.
- To determine the independent effect of initial antimicrobial therapy appropriateness on 28-day mortality.
Main Methods:
- A cohort of 904 patients with microbiologically confirmed severe sepsis or septic shock was analyzed.
- Inappropriate initial antimicrobial therapy was defined as lack of susceptible antimicrobial agents within 24 hours of diagnosis.
- Propensity scores were used to adjust for confounding factors in multivariable models.
Main Results:
- 23% of patients received inappropriate initial antimicrobial therapy.
- Factors associated with inappropriate treatment included European site, surgical admission, and nosocomial or polymicrobial infections.
- Inappropriate therapy was independently associated with increased 28-day mortality (OR=1.8; 95% CI: 1.2-2.6).
Conclusions:
- Appropriate initial antimicrobial therapy is a critical determinant of survival in severe sepsis.
- Improved strategies for early sepsis detection and timely, effective treatment are essential.
- This study underscores the importance of antimicrobial stewardship in sepsis management.
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