Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study.

Christoph Lübbert,Annette Moter,Jürgen Feisthammel,Norman Lippmann,Karolin Wendt,Albrecht Hoffmeister,Joachim Mössner,Arne C Rodloff,Thilo Busch,Gianfranco D Alpini

doi:10.1371/journal.pone.0155479

Abstract

BackgroundPlastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance.MethodsPatients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH).ResultsAmong 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1–1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates.ConclusionsEnterococci and Candida species play an important role in the microbial colonization of biliary stents. Therefore, empirical antimicrobial treatment of stent-associated cholangitis should be guided toward enterococci, Enterobacteriaceae, streptococci, anaerobes, and Candida. To determine causative pathogens, an accurate microbiological analysis of the extracted stent(s) may be helpful.

Highlights

Obstruction of the biliary system by malignancies, anastomotic stenosis after liver transplantation, chronic pancreatitis, or gallstones that are not immediately extractable endoscopically prevents the drainage of bile fluids from the liver and gall bladder to the small intestine and results in obstructive jaundice [1,2,3]
Vancomycinresistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates
Enterococci and Candida species play an important role in the microbial colonization of biliary stents

Summary

Introduction

Obstruction of the biliary system by malignancies, anastomotic stenosis after liver transplantation, chronic pancreatitis, or gallstones that are not immediately extractable endoscopically prevents the drainage of bile fluids from the liver and gall bladder to the small intestine and results in obstructive jaundice [1,2,3]. Gold standard for palliative treatment of an obstructed bile duct is the insertion of a stent by endoscopic retrograde cholangiopancreatography (ERCP) to restore bile fluid drainage [2,3]. The risk for stent occlusion depends on the indwelling time of the stent [1,2,3,8,10]. Most endoscopy units perform stent exchanges at a programmed interval of three months to avoid stent occlusion [2,10,11]. Self-expanding metal stents may double the patency time as compared to straight polyethylene stents [12]. Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. We aimed to assess the current bacterial and fungal etiology of stentassociated biofilms, with particular emphasis on antimicrobial resistance

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