Hepatology : official journal of the American Association for the Study of Liver Diseases
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Multicenter Study
Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis.
It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. ⋯ In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured.
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Bacterial infections are an important cause of mortality in cirrhosis, but there is a paucity of multicenter studies. The aim was to define factors predisposing to infection-related mortality in hospitalized patients with cirrhosis. A prospective, cohort study of patients with cirrhosis with infections was performed at eight North American tertiary-care hepatology centers. Data were collected on admission vitals, disease severity (model for endstage liver disease [MELD] and sequential organ failure [SOFA] scores), first infection site, type (community-acquired, healthcare-associated [HCA] or nosocomial), and second infection occurrence during hospitalization. The outcome was mortality within 30 days. A multivariate logistic regression model predicting mortality was created. 207 patients (55 years, 60% men, MELD 20) were included. Most first infections were HCA (71%), then nosocomial (15%) and community-acquired (14%). Urinary tract infections (52%), spontaneous bacterial peritonitis (SBP, 23%) and spontaneous bacteremia (21%) formed the majority of the first infections. Second infections were seen in 50 (24%) patients and were largely preventable: respiratory, including aspiration (28%), urinary, including catheter-related (26%), fungal (14%), and Clostridium difficile (12%) infections. Forty-nine patients (23.6%) who died within 30 days had higher admission MELD (25 versus 18, P < 0.0001), lower serum albumin (2.4 g/dL versus 2.8 g/dL, P = 0.002), and second infections (49% versus 16%, P < 0.0001) but equivalent SOFA scores (9.2 versus 9.9, P = 0.86). The case fatality rate was highest for C. difficile (40%), respiratory (37.5%), and spontaneous bacteremia (37%), and lowest for SBP (17%) and urinary infections (15%). The model for mortality included admission MELD (odds ratio [OR]: 1.12), heart rate (OR: 1.03) albumin (OR: 0.5), and second infection (OR: 4.42) as significant variables. ⋯ Potentially preventable second infections are predictors of mortality independent of liver disease severity in this multicenter cirrhosis cohort.