Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis*

ObjectivesOur primary goal was to evaluate the impact on in-hospital mortality rate of adequate empirical antibiotic therapy, after controlling for confounding variables, in a cohort of patients admitted to the intensive care unit (ICU) with sepsis. The impact of adequate empirical antibiotic therapy on early (<3 days), 28-day, and 60-day mortality rates also was assessed. We determined the risk factors for inadequate empirical antibiotic therapy. DesignProspective cohort study. SettingICU of a tertiary hospital. PatientsAll the patients meeting criteria for sepsis at admission to the ICU. InterventionsNone. Measurements and Main ResultsFour hundred and six patients were included. Microbiological documentation of sepsis was obtained in 67% of the patients. At ICU admission, sepsis was present in 105 patients (25.9%), severe sepsis in 116 (28.6%), and septic shock in 185 (45.6%). By multivariate analysis, predictors of in-hospital mortality were Sepsis-related Organ Failure Assessment (SOFA) score at ICU admission (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.19–1.40), the increase in SOFA score over the first 3 days in the ICU (OR, 1.40; 95% CI, 1.19–1.65), respiratory failure within the first 24 hrs in the ICU (OR, 3.12; 95% CI, 1.54–6.33), and inadequate empirical antimicrobial therapy in patients with “nonsurgical sepsis” (OR, 8.14; 95% CI, 1.98–33.5), whereas adequate empirical antimicrobial therapy in “surgical sepsis” (OR, 0.37; 95% CI, 0.18–0.77) and urologic sepsis (OR, 0.14; 95% CI, 0.05–0.41) was a protective factor. Regarding early mortality (<3 days), factors associated with fatality were immunosuppression (OR, 4.57; 95% CI, 1.69–13.87), chronic cardiac failure (OR, 9.83; 95% CI, 1.98–48.69) renal failure within the first 24 hrs in the unit (OR, 8.63; 95% CI, 3.31–22.46), and respiratory failure within the first 24 hrs in the ICU (OR, 12.35; 95% CI, 4.50–33.85). Fungal infection (OR, 47.32; 95% CI, 5.56–200.97) and previous antibiotic therapy within the last month (OR, 2.23; 95% CI, 1.1–5.45) were independent variables related to administration of inadequate antibiotic therapy. ConclusionsIn patients admitted to the ICU for sepsis, the adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome, although early mortality rate was unaffected by the appropriateness of empirical antibiotic therapy.

[1]  S. Opal,et al.  Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. , 1996, The New England journal of medicine.

[2]  H T Sørensen,et al.  Antibiotic therapy and outcome of monomicrobial gram-negative bacteraemia: a 3-year population-based study. , 1997, Scandinavian journal of infectious diseases.

[3]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .

[4]  G Sherman,et al.  The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. , 2000, Chest.

[5]  J. Singer,et al.  A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome. , 1993, Chest.

[6]  OLAND,et al.  TREATMENT OF SEPTIC SHOCK WITH THE TUMOR NECROSIS FACTOR RECEPTOR : Fc FUSION PROTEIN C , 2000 .

[7]  D. Pittet,et al.  Importance of pre-existing co-morbidities for prognosis of septicemia in critically ill patients , 1993, Intensive Care Medicine.

[8]  J Ean,et al.  Efficacy and safety of recombinant human activated protein C for severe sepsis. , 2001, The New England journal of medicine.

[9]  E. P. Dellinger,et al.  Quality Standard for the Treatment of Bacteremia , 1994, Infection Control &#x0026; Hospital Epidemiology.

[10]  R. Wenzel,et al.  Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units. , 1998, Critical care medicine.

[11]  J. Rello,et al.  Nosocomial bacteremia in a medical-surgical intensive care unit: Epidemiologic characteristics and factors influencing mortality in 111 episodes , 1994, Intensive Care Medicine.

[12]  J. Rello,et al.  International Conference for the Development of Consensus on the Diagnosis and Treatment of Ventilator-associated Pneumonia. , 2001, Chest.

[13]  J. Miro,et al.  Nosocomial bacteremia in a large Spanish teaching hospital: analysis of factors influencing prognosis. , 1988, Reviews of infectious diseases.

[14]  F. J. Caballero,et al.  Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  Management of deep Candida infection in surgical and intensive care unit patients. British Society for Antimicrobial Chemotherapy Working Party. , 1994, Intensive care medicine.

[16]  D. Denning,et al.  Management of deepCandida infection in surgical and intensive care unit patients , 1994, Intensive Care Medicine.

[17]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[18]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[19]  N. MacIntyre,et al.  A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group. , 1995, Critical care medicine.

[20]  R. Bone.  Guidelines for the Use of Innovative Therapies in Sepsis , 1993 .

[21]  D. Dunn,et al.  Antibiotic treatment for surgical peritonitis. , 1991, Annals of surgery.

[22]  François Gouin,et al.  Incidence, Risk Factors, and Outcome of Severe Sepsis and Septic Shock in Adults: A Multicenter Prospective Study in Intensive Care Units , 1995 .

[23]  J. Quintana,et al.  A predictive model for the treatment approach to community-acquired pneumonia in patients needing ICU admission , 1996, Intensive Care Medicine.

[24]  J. Rello,et al.  The value of routine microbial investigation in ventilator-associated pneumonia. , 1997, American journal of respiratory and critical care medicine.

[25]  J. Rello,et al.  Associations between empirical antimicrobial therapy at the hospital and mortality in patients with severe community-acquired pneumonia , 2002, Intensive Care Medicine.

[26]  David W. Hosmer,et al.  Applied Logistic Regression , 1991 .

[27]  D. Pittet,et al.  Association of secondary and polymicrobial nosocomial bloodstream infections with higher mortality , 1993, European Journal of Clinical Microbiology and Infectious Diseases.

[28]  P. Peduzzi,et al.  Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. , 1997, JAMA.

[29]  A. Torres,et al.  Severe community-acquired pneumococcal pneumonia – what might be done better , 1999, Intensive Care Medicine.

[30]  J. Vincent,et al.  Influence of an anti‐tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis , 1993, Critical care medicine.

[31]  J. Vincent,et al.  Septic shock without documented infection: an uncommon entity with a high mortality , 1999, Intensive Care Medicine.

[32]  Shigeto Oda,et al.  Comparison of Sepsis-related Organ Failure Assessment (SOFA) score and CIS (cellular injury score) for scoring of severity for patients with multiple organ dysfunction syndrome (MODS) , 2000, Intensive Care Medicine.

[33]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[34]  R. Auckenthaler,et al.  Bedside prediction of mortality from bacteremic sepsis. A dynamic analysis of ICU patients. , 1996, American journal of respiratory and critical care medicine.

[35]  J. Rello,et al.  Polymicrobial bacteremia in critically ill patients , 2005, Intensive Care Medicine.

[36]  P. Peduzzi,et al.  Community-Acquired Bacterial Meningitis: Risk Stratification for Adverse Clinical Outcome and Effect of Antibiotic Timing , 1998, Annals of Internal Medicine.

[37]  J. Vallés,et al.  Nosocomial bacteremia in critically ill patients: a multicenter study evaluating epidemiology and prognosis. Spanish Collaborative Group for Infections in Intensive Care Units of Sociedad Espanola de Medicina Intensiva y Unidades Coronarias (SEMIUC). , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[38]  Corinne Alberti,et al.  Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study , 2002, Intensive Care Medicine.

[39]  E. Abraham,et al.  Microbiologic findings and correlations with serum tumor necrosis factor-alpha in patients with severe sepsis and septic shock. , 1999, The Journal of infectious diseases.

[40]  C. VandenBussche,et al.  Epidemiological features and prognosis of severe community-acquired pneumococcal pneumonia , 1999, Intensive Care Medicine.

[41]  F Doyon,et al.  Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. , 1995, JAMA.

[42]  J. Vincent,et al.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure , 1996, Intensive Care Medicine.

[43]  J. Marshall,et al.  Source control in the management of sepsis , 2001, Intensive Care Medicine.

[44]  E. P. Dellinger,et al.  Quality Standard for the Treatment of Bacteremia , 1994, Infection Control &#x0026; Hospital Epidemiology.

[45]  D. Maki,et al.  A semiquantitative culture method for identifying intravenous-catheter-related infection. , 1977, The New England journal of medicine.

[46]  G Sherman,et al.  Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. , 1999, Chest.

[47]  F Doyon,et al.  Bacteremia and severe sepsis in adults: a multicenter prospective survey in ICUs and wards of 24 hospitals. French Bacteremia-Sepsis Study Group. , 1996, American journal of respiratory and critical care medicine.

[48]  R. Wenzel,et al.  Etiologic organisms as independent predictors of death and morbidity associated with bloodstream infections. , 1987, The Journal of infectious diseases.

[49]  S. Ünal,et al.  Factors influencing prognosis in bacteremia due to gram-negative organisms: evaluation of 448 episodes in a Turkish university hospital. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[50]  C. Sprung,et al.  Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. , 1998, Critical care medicine.

[51]  Soumitra R. Eachempati,et al.  Gender-based differences in outcome in patients with sepsis. , 1999, Archives of surgery.