[show abstract][hide abstract] ABSTRACT: Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern.
To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock.
Retrospective, propensity matched, multicenter, cohort study.
Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007.
A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated.
The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with beta-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days.
Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.
Critical care medicine 09/2010; 38(9):1773-85. · 6.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock.
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.
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).
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.
[show abstract][hide abstract] ABSTRACT: To describe the incidence and outcomes associated with early acute kidney injury (AKI) in septic shock and explore the association between duration from hypotension onset to effective antimicrobial therapy and AKI.
Retrospective cohort study.
A total of 4,532 adult patients with septic shock from 1989 to 2005.
Intensive care units of 22 academic and community hospitals in Canada, the United States and Saudi Arabia.
In total, 64.4% of patients with septic shock developed early AKI (i.e., within 24 h after onset of hypotension). By RIFLE criteria, 16.3% had risk, 29.4% had injury and 18.7% had failure. AKI patients were older, more likely female, with more co-morbid disease and greater severity of illness. Of 3,373 patients (74.4%) with hypotension prior to receiving effective antimicrobial therapy, the median (IQR) time from hypotension onset to antimicrobial therapy was 5.5 h (2.0-13.3). Patients with AKI were more likely to have longer delays to receiving antimicrobial therapy compared to those with no AKI [6.0 (2.3-15.3) h for AKI vs. 4.3 (1.5-10.8) h for no AKI, P < 0.0001). A longer duration to antimicrobial therapy was also associated an increase in odds of AKI [odds ratio (OR) 1.14, 95% CI 1.10-1.20, P < 0.001, per hour (log-transformed) delay]. AKI was associated with significantly higher odds of death in both ICU (OR 1.73, 95% CI 1.60-1.9, P < 0.0001) and hospital (OR 1.62, 95% CI, 1.5-1.7, P < 0.0001). By Cox proportional hazards analysis, including propensity score-adjustment, each RIFLE category was independently associated with a greater hazard ratio for death (risk 1.31; injury 1.45; failure 1.56).
Early AKI is common in septic shock. Delays to appropriate antimicrobial therapy may contribute to significant increases in the incidence of AKI. Survival was considerably lower for septic shock associated with early AKI, with increasing severity of AKI, and with increasing delays to appropriate antimicrobial therapy.
European Journal of Intensive Care Medicine 01/2009; 35(5):871-81. · 5.17 Impact Factor