Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.
OBJECTIVE
Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock.


METHODS
The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries.


RESULTS
Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). 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 < 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).


CONCLUSIONS
Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
Kumar
Anand
A
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada; Cooper Hospital/University Medical Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden. Electronic address: akumar61@yahoo.com.
Ellis
Paul
P
Department of Emergency Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
Arabi
Yaseen
Y
Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Roberts
Dan
D
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
Light
Bruce
B
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
Parrillo
Joseph E
JE
Cooper Hospital/University Medical Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden.
Dodek
Peter
P
Section of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
Wood
Gordon
G
Critical Care Medicine, Royal Jubilee and Victoria General Hospitals, Vancouver Island Health Authority, Victoria, BC, Canada.
Kumar
Aseem
A
Biomolecular Sciences Program and Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada.
Simon
David
D
Section of Infectious Diseases, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL.
Peters
Cheryl
C
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
Ahsan
Muhammad
M
Section of Critical Care Medicine, Health Sciences Centre/St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
Chateau
Dan
D
Biostatistical Consulting Unit, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
D000900:Anti-Bacterial Agents / Q000633:toxicity*; D015897:Comorbidity; D006801:Humans; D016017:Odds Ratio; D012189:Retrospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate
D000900:Anti-Bacterial Agents