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

被引:71
|
作者
Lebeaux, David [1 ,2 ]
Merabishvili, Maia [3 ,4 ]
Caudron, Eric [5 ,6 ]
Lannoy, Damien [7 ,8 ]
Van Simaey, Leen [4 ]
Duyvejonck, Hans [4 ,9 ]
Guillemain, Romain [10 ]
Thumerelle, Caroline [11 ]
Podglajen, Isabelle [1 ,12 ]
Compain, Fabrice [1 ,12 ]
Kassis, Najiby [13 ]
Mainardi, Jean-Luc [1 ,12 ]
Wittmann, Johannes [14 ]
Rohde, Christine [14 ]
Pirnay, Jean-Paul [3 ]
Dufour, Nicolas [15 ]
Vermeulen, Stefan [9 ]
Gansemans, Yannick [16 ]
Van Nieuwerburgh, Filip [16 ]
Vaneechoutte, Mario [4 ]
机构
[1] Univ Paris, F-75006 Paris, France
[2] Hop Europeen Georges Pompidou, AP HP, Serv Microbiol, Unite Mobile Infectiol, 20 Rue Leblanc, F-75015 Paris, France
[3] Queen Astrid Mil Hosp, Lab Mol & Cellular Technol, Bruynstr 1, B-1120 Brussels, Belgium
[4] Univ Ghent, Fac Med & Hlth Sci, Lab Bacteriol Res, C Heymanslaan 10, B-9000 Ghent, Belgium
[5] Hop Europeen Georges Pompidou, AP HP, Serv Pharm, Ctr Univ Paris, 20 Rue Leblanc, F-75015 Paris, France
[6] Univ Paris Saclay, Lipides Syst Analyt & Biol, F-92296 Chatenay Malabry, France
[7] CHU Lille, Inst Pharm, F-59000 Lille, France
[8] Univ Lille, ULR7365, GRITA Grp Rech Formes Injectables & Technol Assoc, F-59000 Lille, France
[9] Univ Coll Ghent, Res Ctr Hlth & Water Technol, Keramiekstr 80, B-9000 Ghent, Belgium
[10] Hop Europeen Georges Pompidou, Serv Anesthesie Reanimat, F-75015 Paris, France
[11] Univ Lille, CHU Lille, Hop Jeanne Flandre, Pediat Pulmonol & Allergy Unit, F-59000 Lille, France
[12] Hop Europeen Georges Pompidou, AP HP, Serv Microbiol, 20 Rue Leblanc, F-75015 Paris, France
[13] Hop Europeen Georges Pompidou, AP HP, Unite Hyg Hosp, Serv Microbiol, 20 Rue Leblanc, F-75015 Paris, France
[14] German Collect Microorganisms & Cell Cultures Gmb, Leibniz Inst DSMZ, Inhoffenstr 7B, D-38124 Braunschweig, Germany
[15] Ctr Hosp Rene Dubos, Serv Reanimat Medicochirurg, F-95300 Pontoise, France
[16] Univ Ghent, Fac Pharmaceut Sci, Lab Pharmaceut Biotechnol, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
来源
VIRUSES-BASEL | 2021年 / 13卷 / 01期
关键词
cystic fibrosis; lung transplantation; antibiotic resistance; Achromobacter xylosoxidans; bacteriophage therapy; PSEUDOMONAS-AERUGINOSA; BACTERIOPHAGES; DELIVERY;
D O I
10.3390/v13010060
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
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.
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页数:10
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