用噬菌体治疗抗泛耐药木糖氧化无色杆菌感染的12岁肺移植囊性纤维化患者的案例研究

A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient

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中文摘要:对肺移植囊性纤维化患者来说,泛耐药细菌会引起高频定植/感染,而噬菌体是一种很有前景的治疗策略。不过,关于使用噬菌体治疗糖氧化无色杆菌感染的临床资料很少。本案例对一个12岁的因肺部持久受到泛耐药木糖氧化无色杆菌感染肺移植囊性纤维化患者,进行了两轮噬菌体治疗。研究发现,临床耐受性良好,但初始支气管肺泡灌洗液(BAL)中仍有木糖氧化无色杆菌;患者呼吸状况逐渐改善,并可停止氧疗;气道低水平木糖氧化无色杆菌持续数月后,转为阴性。停止噬菌体治疗和亚胺培南治疗后两年多没有复发。在噬菌体治疗过程中收集到八株木糖氧化无色杆菌,全基因组测序表明分别属于四种已知菌株,其中一种菌株的噬菌体受体基因停止了突变。对不同支气管肺泡灌洗液进行菌株特异性qPCR检测以记录肺定殖动力学。本文报告了首例用噬菌体治疗感染木糖氧化无色杆菌的肺移植患者。气道定植的动力学涉及到菌体敏感株和噬菌体耐药株,比从细菌培养所推断的更为复杂。
外文摘要:Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient's respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.
外文关键词:cystic fibrosis;lung transplantation;antibiotic resistance;Achromobacter xylosoxidans;bacteriophage therapy
作者:Lebeaux, D;Merabishvili, M;Caudron, E;Lannoy, D;Van Simaey, L;Duyvejonck, H;Guillemain, R;Thumerelle, C;Podglajen, I;Compain, F;Kassis, N;Mainardi, JL;Wittmann, J;Rohde, C;Pirnay, JP;Dufour, N;Vermeulen, S;Gansemans, Y;Van Nieuwerburgh, F;Vaneechoutte, M
作者单位:Univ Pari;Hop Europeen Georges Pompidou;Queen Astrid Mil Hosp;Univ Ghent;Univ Paris Saclay;CHU Lille; Univ Coll Ghent;;German Collect Microorganisms & Cell Cultures Gmb;Ctr Hosp Rene Dubos
期刊名称:VIRUSES-BASEL
期刊影响因子:3.816
出版年份:2021
出版刊次:1
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  1. 编译服务:噬菌体
  2. 编译者:虞德容
  3. 编译时间:2021-03-18