Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis☆
Section snippets
Study sample
We used a multicenter database of 1342 patients (aged >18 years) with severe sepsis or early septic shock who were enrolled in a double-blind, placebo-controlled phase 3 trial of the safety and efficacy of lenercept (p55 immunoglobulin G tumor necrosis factor receptor fusion protein) (20). The study was conducted in 108 community and university-affiliated hospitals in the United States (n = 60), Canada (n = 6), and Europe (n = 42). Overall, there was no difference in 28-day mortality between
Results
Of the 1342 patients, 904 (67%) had microbiologically documented severe sepsis or early septic shock and were included in the study. The mean (± SD) patient age was 60 ± 17 years; 548 patients (61%) were male. The mean SAPS II–predicted 28-day mortality was 34% ± 19%. There was no baseline organ dysfunction in 204 patients (23%), whereas 410 patients (45%) had dysfunction of one organ, 209 (23%) had dysfunction of two organs, and 81 (9%) had dysfunction of three or more organs. Respiratory
Discussion
This study evaluated the effect of inadequate initial antimicrobial treatment on outcome in critically ill patients with microbiologically documented severe sepsis or early septic shock. We found that both the severity of illness and the number of organ dysfunctions at baseline proved to be strong prognostic indicators of mortality. After adjusting for confounding, inappropriate antimicrobial treatment was associated with increased mortality. Thus, adequacy of antimicrobial therapy was an
Acknowledgements
We are grateful to the many investigators and staff who were involved in enrolling patients in this clinical trial and whose detailed record-keeping enabled the analysis reported here. In particular, we would like to thank the other members of the Geneva Sepsis Network (J. C. Chevrolet, J. M. Dayer, P. Eggimann, T. Fumeaux, B. Ricou, and P. Suter) for their help and collaboration.
References (38)
- et al.
Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients
Am J Med
(1980) - et al.
Inadequate antimicrobial treatment of infectionsa risk factor for hospital mortality among critically ill patients
Chest
(1999) - et al.
The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting
Chest
(2000) - et al.
The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an intensive care unit
Clin Microbiol Infect
(2003) - et al.
Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia
Chest
(1997) - et al.
Antimicrobial misuse in patients with positive blood cultures
Am J Med
(1989) - et al.
The clinical significance of positive blood cultures in the 1990sa prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults
Clin Infect Dis
(1997) Inadequate antimicrobial treatmentan important determinant of outcome for hospitalized patients
Clin Infect Dis
(2000)Appropriate use of antimicrobial agentschallenges and strategies for improvement
Crit Care Med
(2003)- et al.
Gram-negative bacteremia. II. Clinical laboratory, and therapeutic observations
Arch Intern Med
(1962)
Analysis of 1186 episodes of Gram-negative bacteremia in non-university hospitalsthe effects of antimicrobial therapy
Rev Infect Dis
An analysis of community and hospital-acquired bacteraemia in a large teaching hospital in the United Kingdom
QJM
How bad are bacteremia and sepsis? Outcomes in a cohort with suspected bacteremia
Arch Intern Med
Bedside prediction of mortality from bacteremic sepsisa dynamic analysis of ICU patients
Am J Respir Crit Care Med
The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient
Am J Respir Crit Care Med
Evaluation of antimicrobial therapy management of 120 consecutive patients with secondary peritonitis
J Antimicrob Chemother
Outcome of postoperative pneumonia in the EOLE study
Intensive Care Med
Long-term survival and function after suspected gram-negative sepsis
JAMA
Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial
JAMA
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The original clinical trial was supported by Hoffmann-La Roche Ltd., Basel, Switzerland. The sponsor had no role in data analysis or in the submission of this report.