O03 Rapid Infection Diagnostics in Cirrhosis (RIDiC): a novel molecular-based approach to address the ever increasing challenge of antimicrobial resistant infections in decompensated cirrhosis and acute-on-chronic liver failure

Abstract

Abstract Background Global prevalence of MDR infections in cirrhotic patients has risen to 34% and associates with worsening clinical trajectory and mortality (Fernandez J et al. 2019). A major unmet need in addressing the challenge of antimicrobial resistance (AMR) in cirrhosis is rapid pathogen diagnosis and antimicrobial resistance (AMR) (Patel VC et al. 2019). These can facilitate selection of more effective antibiotic therapy, reducing selection for MDR organisms. The Curetis Unyvero™ platform (CUp) employs multiplex PCR technology for pathogen and AMR gene detection from multiple bodily tissues and fluids requiring minimal pre- processing. The investigator-initiated pilot study aimed to assess the utility of this platform for hospitalized cirrhotic patients. Methods Ascitic fluid, bronchoalveolar lavage (BAL) and blood culture samples were obtained from hospitalized cirrhotic patients with acute decompensation (AD) or acute-on-chronic liver failure (ACLF), in whom there was clinical suspicion of infection. Samples were tested using the IAI (intra-abdominal infection) panel, HPN (hospital pneumonia) panel and BCU (blood culture) panel based on sample type available. Results were not shared with clinicians for decision-making. Data were compared with standard microbiology diagnostics. Results 31 samples from 21 patients were tested: ascites (25), BAL (4), blood culture (2). Time to positive culture result of all samples was reduced with CUp compared with standard microbiology (4.59 versus 73.5 h). CUp showed 100% specificity (12/12) and detected the same organism in 100% of cases (10/12). In 6 samples, CUp identified pathogens which were consistent with clinical evidence of spontaneous bacterial peritonitis and previous positive isolates which standard microbiological diagnostics failed to identify. AMR genes identified by the CUp correlated with AMR patterns reported by standard diagnostics in 100% (5/5) of cases. In 2 patients, broad-spectrum antibiotic therapy continued although the CUp supported infection resolution. Four patients in whom CUp screening was negative continued to receive antibiotics whilst awaiting negative standard cultures that arrived 72 h later. CUp did not identify an Aspergillus species in one BAL sample as this is not part of the BAL panel. Conclusions These preliminary data suggest CUp results are compatible with standard laboratory diagnostics. The CUp may be utilized for earlier infection diagnosis and improve the targeting and de-escalation of antimicrobial therapy in AD and ACLF. These are crucial components in enhancing antibiotic stewardship strategies and to reduce MDR infections (Figure 1). Further work is however required to evaluate cost implications, validation and impact on clinical outcomes and mortality in cirrhosis.