Exploring the Prevalence, Predictors and Impact of Bacterial Infections and Guiding Empiric Antimicrobial Decisions in Acutely Decompensated Cirrhosis (EPIC-AD): A-seminal

Background and Aim: We attempted to satisfy the unmet need of identifying epidemiology, risk factors and impact of infections in cirrhosis patients. Methods: We recruited acutely decompensated cirrhosis patients at a tertiary-centre ambi-spectively (2013-2023). We defined infections by the EASL criteria. Clinical characteristics, microbiological details with site of infection and multi-drug resistant organisms (MDROs), and 30-day mortality were noted. Result: We enrolled 971 patients, aged 45years, 87% males, with alcoholic hepatitis (47%), and ethanol-related disease (67%). 675 patients (69.5%) had infections, of which 305(45%) were culture-proven and the commonest bacteria being gram-negative in 68.5% patients. Of proven cases, 71% were infected with MDROs with maximum prevalence of carbapenem-resistant bacterial infections (48%). MDROs were maximally noted among cases with pulmonary infections (80.5%) and SSTIs (76.5%). Site-wise distribution of isolates were described for guiding empiric antimicrobials. A model including hospitalization (OR:2.23), norfloxacin-use (OR:2.26), broad-spectrum antibiotics-exposure (OR:1.61) in last 3months, SIRS (OR:1.75), procalcitonin (OR:4.64), and HE-grade (OR:1.41) could predict infection in overall cohort with AUC of 0.891. Among infected patients, second infection (OR:7.19), norfloxacin-prophylaxis (OR:2.76), antibiotic-use (OR:1.66), rifaximin (OR:0.44), CLIF-C-OF (OR:1.10), multi-site (OR:3.67) and polymicrobial infections (OR: 4.55) could predict MDRO infections with AUC of 0.779 and specificity of 93%. Infections-culture-proven or probable, either as acute precipitant or second infection, MDROs, carbapenem or pan-drug resistance; all were independently associated with mortality after adjusting for age, leucocytosis, and organ failures (p<0.001, each). A model with age (HR:1.02), infection (HR:1.52), prior hospitalization (HR:5.33), norfloxacin (HR:1.29), multisite infection (HR:1.47), and CLIF-C OF (HR:1.17) could predict mortality with C-statistics of 0.782 (p<0.05, each). Conclusion: In a large Indian study among cirrhosis, a disturbingly high burden and negative impact of infections by MDROs, especially carbapenem resistant bacteria demands for an urgent control measures. Site wise epidemiology of infections and risk stratification models will guide appropriate empiric antimicrobial decisions in cirrhosis.