Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis

AIM:To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis.METHODS:We performed a prospective study of 127patients who underwent endoscopic retrograde cholangiopancreatography,for various biliary disorders,at 3 tertiary referral centers in Germany from July 2011through July 2012(ClinicalTrials.gov:NCT01109550).Bile,buccal,and stool samples were collected.When indicated,endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections.RESULTS:Candida species were detected in 38 of the 127 bile samples(29.9%).By multivariate analysis patients’age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis(P<0.05).Patients with immunosuppression(P=0.058)and recent long-term antibiotic therapy(>7 d)(P=0.089)tend to be at risk for biliary candidiasis.One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically.Of Candida subspecies detected,36.7%were azole-resistant,such as C glabrata.Eight patients received anti-mycotic therapy,based on our algorithm.Of these,3 had cancer with biliary tract involvement,2had secondary sclerosing cholangitis,1 had retroperitoneal fibrosis,and 5 had septicemia.In all patients contamination was ruled out by smears of the endoscope channel.CONCLUSION:Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders.Our suggested algorithm facilitates the further clinical management.

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 CMCblood in 5/8(62.5%)with clinical signs of infection.mRTPCR_(bile),CMC_(bile),and CMCblood 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-PC_(Rbile)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.