Lübbert Christoph, Wendt Karolin, Feisthammel Jürgen, Moter Annette, Lippmann Norman, Busch Thilo, Mössner Joachim, Hoffmeister Albrecht, Rodloff Arne C
Interdisciplinary Endoscopy Unit, Department of Gastroenterology and Rheumatology, Leipzig University Hospital, Liebigstr. 20, D-04103 Leipzig, Germany.
Division of Infectious Diseases and Tropical Medicine, Department of Gastroenterology and Rheumatology, Leipzig University Hospital, Liebigstr. 20, D-04103 Leipzig, Germany.
PLoS One. 2016 May 12;11(5):e0155479. doi: 10.1371/journal.pone.0155479. eCollection 2016.
Plastic 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.
Patients 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).
Among 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.
Enterococci 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.
用于治疗胆道梗阻的塑料支架会因微生物定植和生物膜形成而随时间发生堵塞。由于抗菌药物使用不当或存在抗菌耐药性,支架相关性胆管炎的治疗往往效果不佳。我们旨在评估支架相关性生物膜当前的细菌和真菌病因,尤其关注抗菌耐药性。
前瞻性纳入需要内镜下放置支架的胆道狭窄患者。取出支架后,通过超声处理破坏生物膜,培养微生物,并通过基质辅助激光解吸/电离飞行时间(MALDI-TOF)质谱分析和/或生化分型鉴定分离株。最后,测定各种抗菌药物的最低抑菌浓度(MIC)。对选定的支架进一步采用荧光原位杂交(FISH)进行分析。
在120例(男性占62.5%,中位年龄64岁)胆道狭窄患者(35%为恶性,65%为良性)中,中位留置时间63天(范围1 - 1274天)后,分析了113个双猪尾聚氨酯支架和100个直形聚乙烯支架。支架堵塞率分别为11.5%和13%,与胆管炎风险显著增加相关(38.5%对9.1%,P<0.001)。检测到95种不同细菌和13种真菌;多微生物定植占主导(95.8%对4.2%,P<0.001)。肠球菌(79.3%)、肠杆菌科(73.7%)和念珠菌属(55.9%)是主要病原体。念珠菌属在先前接受过长期抗生素治疗的患者中更常见(63%对46.7%,P = 0.023)。耐万古霉素肠球菌占13.7%,产超广谱β-内酰胺酶(ESBL)且对环丙沙星耐药的肠杆菌科占13.9%,耐唑类念珠菌属占各自分离株的32.9%。
肠球菌和念珠菌属在胆道支架的微生物定植中起重要作用。因此,支架相关性胆管炎的经验性抗菌治疗应以针对肠球菌、肠杆菌科、链球菌、厌氧菌和念珠菌为导向。为确定致病病原体,对取出的支架进行准确的微生物学分析可能会有帮助。