NEW YORK (Reuters Health) – The initial empiric antimicrobial therapy used to treat septic shock may be the most important determinant of whether a patient will survive to hospital discharge. Inappropriate therapy can reduce the chances of survival by fivefold or more, according to an article in the November issue of Chest.

The research team, led by Dr. Anand Kumar at the University of Manitoba in Winnipeg, Canada, conducted a multicenter retrospective review of data on 5715 consecutive adult patients with septic shock.

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.”

Appropriate empiric antimicrobial therapy was started in 80% of cases.

Survival to hospital discharge with appropriate initial therapy was 52%. The rate fell to 10.3% with inappropriate initial therapy (p < 0.0001). The difference in survival was doubled for culture-negative cases. The decrease in survival with the wrong initial treatment ranged from 2.3-fold for pneumococcal infection to 17.6-fold for primary bloodstream infections. 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).” Dr. Kumar and colleagues identified significant variations between groups of clinical infections and organisms. For example, urinary tract and skin and soft-tissue infections had the best initial coverage at around 85%, whereas catheter-associated and primary blood stream infection had the worst at about 69%. Initial antibiotic therapy was deemed appropriate for roughly 80% of bacteria, but only 44% of fungal organisms. “The empiric selection of antimicrobial agents must be a central element in any efforts to address the suboptimal management of this condition,” the research team concludes. Reference:
Chest 2009;136:1237-1248.