A Multipathogen Bile Sample-based PCR Assay Can Guide Empirical Antimicrobial Strategies in Cholestatic Liver Diseases

BACKGROUND AND OBJECTIVES: Polymerase chain reaction (PCR) techniques provide rapid detection of pathogens. This pilot study evaluated the diagnostic utility and clinical impact of multiplex real-time PCR (mRT-PCR, SeptiFast) vs. conventional microbial culture (CMC) in bile samples of patients with chronic cholestatic liver diseases (cCLDs), endoscopic retrograde cholangio-pancreatography (ERCP), and peri-interventional-antimicrobial-prophylaxis (pAP). METHODS: We prospectively collected bile samples from 26 patients for microbiological analysis by CMC and mRT-PCR. Concordance of the results of both methods was determined by Krippendorff's alpha (α) for inter-rater reliability and the Jaccard index of similarity. RESULTS: mRT-PCR(bile) and CMC(bile) results were concordant for only Candida albicans (α=0.8406; Jaccard index=0.8181). mRT-PCR(bile) detected pathogens in 8/8 cases (100%), CMC(bile) in 7/8 (87.5%), and CMC(blood) in 5/8 (62.5%) with clinical signs of infection. mRT-PCR(bile), CMC(bile), and CMC(blood) had identical detection results in 3/8 (37.5%) with clinical signs of infection (two Klebsiella spp. and one Enterococcus faecium). The total pathogen count was significantly higher with mRT-PCR(bile) than with CMC(bile) (62 vs. 31; χ(2)=30.031, p<0.001). However, pathogens detected by mRT-PCR(bile) were more often susceptible to pAP according to the patient infection/colonization history (PI/CH) and surveillance data for antibiotic resistance in our clinic (DARC). Pathogens identified by mRT-PCR(bile) and resistant to pAP by PI/CH and DARC were likely to be clinically relevant. CONCLUSIONS: mRT-PCR in conjunction with CMCs for bile analysis increased diagnostic sensitivity and may benefit infection management in patients with cholestatic diseases. Implementation of mRT-PCR in a bile sample-based diagnostic routine can support more rapid and targeted use of antimicrobial agents in cCLD-patients undergoing ERCP and reduce the rate/length of unnecessary administration of broad-spectrum antibiotics.