Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis.

By S. Harbarth, J. Garbino, J. Pugin, J. Romand, D. Lew, Didier Pittet. American Journal of Medicine, 2003

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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.

Subfields: Critical Care and Intensive Care Medicine, Epidemiology, Public Health, Environmental and Occupational Health

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Citations in the corpus

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria (2012, background): “The use of at least one antimicrobial agent to which a pathogen is susceptible for empiric therapy leads to lower mortality and improved outcomes in patients with sepsis caused by Gram-negative bacteria, as observed in a number of studies (6, 33, 46, 48, 84, 89, 106, 108, 133, 137, 140, 153, 158, 17”
Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome (2004, background): “route of administration conformed with current medical standards (6).”
Delaying the Empiric Treatment of Candida Bloodstream Infection until Positive Blood Culture Results Are Obtained: a Potential Risk Factor for Hospital Mortality (2005, background): “Three recent studies of patients with severe sepsis, many of whom had bloodstream infections, including fungal bloodstream infections, also demonstrated that inappropriate initial antimicrobial therapy was associated with greater hospital mortality (6, 8, 10).”
Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Antibiotic Therapy for Sepsis (2010, methodology): “Two studies included a propensity score for appropriate empirical treatment in the multivariable analysis (33, 54), and one study performed a propensity-matched analysis (23, 74).”
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Summary of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship (2007, background): “24%) [106] and critically ill ICU patients (42% vs.”
Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. (2006, background): “Appropriateness of initial antibiotic therapy was defined as previously described (31).”