Abstract

Background: Regional differences in environment, health-care system, microbiology lab capabilities, countermeasures of drug resistance may greatly impact the occurrence and evolution of infection in cirrhosis. We aimed to assess the prevalence, characteristics, clinical impact, and variations in infection on admission (AdI) across a global population of cirrhosis inpatients.

Methods: CLEARED Consortium prospectively recruited inpts with cirrhosis from 6 continents. Data were collected at baseline and followed during admission. Infections diagnosed empirically or by culture using prespecified criteria within 48 hrs of admission were defined as AdI. Comparisons were made between pts w/wo AdI & between regions. Multivariable (MV) analysis for in-hospital mortality was performed using admission variables.

Results: AdI was identified in 1351 pts (32%) among 4238 pts from 27 countries. Major site was SBP (28.9%), respiratory (RTI, 17.3%) & UTI (14.3%). No organism was isolated in 48%, then G- (25%), G+(11%) & fungal (3%). Among 580 AdI pts with isolated organisms, 20% had drug-resistant organisms (DRO).

AdI vs No-AdI admission variables: AdI and No-AdI pts had similar demographics and etiology of cirrhosis but ↑ MELD-Na (24 vs 19, p<0.001), prior infections (33 vs 13%), ascites (69 vs 61%), overt HE (32 vs 24%), AKI (20 vs 14%) and transplant listing (11 vs 9%), all p<0.01. AdI pts had ↑ use of lactulose (49 vs 39%), rifaximin (30 vs 21%), diuretics (57 vs 52%) and SBP Prophylaxis (16 vs 12%), all p<0.001. AdI pts had ↑ HE (42 vs 32%), AKI (37 vs 17%), anasarca (43 vs 35%), & lower GI bleed (18 vs 28%) as causes of admission, all p<0.01.

Outcomes: AdI pts developed ↑ nosocomial infections (17 vs 11%), AKI (47 vs 28%), brain (19 vs 9%), respiratory (15 vs 6%) and circulatory failures (19 vs 7%), ICU transfers (25 vs 15%) and in-hospital (21 vs 7%), all p<0.001. MV analysis identified AdI as a significant risk factor for in-hospital mortality (OR 2.78, p<0.0001) independent of age (OR, 1.02, p<0.001) baseline MELD-Na (OR 1.15, p<0.001), prior GI bleed (OR 1.3 p=0.03) and prior HCC (OR 2.00, p=0.002), etc.

Regional variations African sites had the highest prevalence of Adl but lowest culture positivity (Fig A, C). SBP was highest in Africa while UTIs were highest in Nth Am (Fig B). RTI was higher in EU, Asia and Australia while skin and soft tissue infection was higher in Sth and Nth Am. The rest were similar. G- were higher in Nth Am & Australia while G+ were similar. Fungi were higher in Asia and America (Fig C). DRO varied across the continents and was influenced by insufficient culture positive isolates (Fig D).

Conclusion: In this global cohort, one-third of the inpts with cirrhosis had AdI which increases risk of in-hospital mortality by ~3 fold. Tailored strategies should be developed for different regions due to the substantially different characteristics in terms of types, culture positivity rates, isolated causative organism(s) and DROs across regions.