Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience

Abstract

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.

Conclusion: Potentially preventable second infections are predictors of mortality independent of liver disease severity in this multicenter cirrhosis cohort.

Figure 1. Distribution of percentage of individual first infections that were community-acquired, health-care associated or nosocomial infections

A significantly higher percentage of the nosocomial first infections were UTI and Clostridium difficile while a significantly lower percentage was due to skin infections and SBP. CA: community-acquired, HCA: health care-associated, Noso: nosocomial

Figure 2. Percentage of infections (first and second) according to body site

The percentage distribution of first and second infections is shown. Blue bars represent the percentage of the first infections by site while red bars represent the second infections. There is a significantly higher percentage prevalence of respiratory (p<0.0001), fungal (p=0.003), and C difficile (p=0.05) in the second infections compared to the first while the opposite was true for SBP (p=0.045), Skin (p=0.02) infections and spontaneous bacteremia (p=0.036). UTI percentage prevalence was similar in the first and second infections (p=0.89). Resp: lower respiratory tract infections, UTI: urinary tract infections, Bact: spontaneous bacteremia