title: Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality.
abstract: BACKGROUND
  Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality.
  
  
  METHODS
  This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT).
  
  
  RESULTS
  We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001).
  
  
  CONCLUSIONS
  β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and septic shock. Administering a combination of antimicrobials with different mechanisms of action is associated with decreased mortality.
authors.forename: Ana
authors.initials: A
authors.lastname: Díaz-Martín
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-González
authors.forename: Ricard
authors.initials: R
authors.lastname: Ferrer
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz-Leyba
authors.forename: Enrique
authors.initials: E
authors.lastname: Piacentini
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Lopez-Pueyo
authors.forename: Ignacio
authors.initials: I
authors.lastname: Martín-Loeches
authors.forename: Mitchell M
authors.initials: MM
authors.lastname: Levy
authors.forename: Antoni
authors.initials: A
authors.lastname: Artigas
authors.forename: José
authors.initials: J
authors.lastname: Garnacho-Montero
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000401:mortality; D003428:Cross Infection / Q000188:drug therapy / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D047090:beta-Lactams / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams