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

Michael Jahn; Mustafa K Özçürümez; Sebastian Dolff; Hana Rohn; Dominik Heider; Alexander Dechêne; Ali Canbay; Peter M Rath; Antonios Katsounas

doi:10.14218/JCTH.2021.00337

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

J Clin Transl Hepatol. 2022 Oct 28;10(5):788-795. doi: 10.14218/JCTH.2021.00337. Epub 2022 Mar 21.

Authors

Michael Jahn¹, Mustafa K Özçürümez², Sebastian Dolff³, Hana Rohn³, Dominik Heider⁴, Alexander Dechêne⁵, Ali Canbay², Peter M Rath⁶, Antonios Katsounas²

Affiliations

¹ Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
² Department of Medicine, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany.
³ Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁴ Department of Mathematics and Computer Science, University of Marburg, Marburg, Germany.
⁵ Department for Internal Medicine, Nuremberg Hospital North, Paracelsus Private Medical University Nuremberg, Nuremberg, Germany.
⁶ Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Abstract

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; χ²=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.

Keywords: Antibiotic prophylaxis; Cholangitis; Cholestasis; ERCP; PCR.