The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p less than 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23).
A Medscape commentary on the paper noted:
They defined appropriate therapy as having in vitro activity against the isolated pathogen, administered as either the first new antimicrobial agent or within 6 hours of the first new agent. In cases of culture-negative septic shock, suitable agents are "concordant with accepted international norms for empiric therapy and modified to local flora."
...Even after adjusting for multiple risk factors (demographics, initial illness severity, major comorbidities, infection site, early fluid resuscitation, and initial vasopressor/inotropic support), "the appropriateness of the first antimicrobial drug remained most strongly associated with outcome (odds ratio 8.99)."
Wow. Shoot first, ask questions later.