title: Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis.
abstract: BACKGROUND
  Genetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients.
  
  
  METHODS
  The inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-alpha 308 promoter polymorphism; the polymorphism in the first intron of the TNF-beta gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission.
  
  
  RESULTS
  A group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy.
  
  
  CONCLUSIONS
  This study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.
authors.affiliation: Intensive Care Unit, Hospital Universitatrio Virgen del Rocio, Seviilla, Spain. jgmrji@arrakis.es
authors.forename: Jose
authors.initials: J
authors.lastname: Garnacho-Montero
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldabo-Pallas
authors.forename: Carmen
authors.initials: C
authors.lastname: Garnacho-Montero
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cayuela
authors.forename: Rocio
authors.initials: R
authors.lastname: Jiménez
authors.forename: Sonia
authors.initials: S
authors.lastname: Barroso
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz-Leyba
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D017052:Hospital Mortality; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10