A Case of Phage Therapy against Pandrug-Resistant <i>Achromobacter xylosoxidans</i> in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient
David Lebeaux,
Maia Merabishvili,
Eric Caudron,
Damien Lannoy,
Leen Van Simaey,
Hans Duyvejonck,
Romain Guillemain,
Caroline Thumerelle,
Isabelle Podglajen,
Fabrice Compain,
Najiby Kassis,
Jean-Luc Mainardi,
Johannes Wittmann,
Christine Rohde,
Jean-Paul Pirnay,
Nicolas Dufour,
Stefan Vermeulen,
Yannick Gansemans,
Filip Van Nieuwerburgh,
Mario Vaneechoutte
Affiliations
David Lebeaux
Université de Paris, F-75006 Paris, France
Maia Merabishvili
Laboratory Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, B-1120 Brussels, Belgium
Eric Caudron
Service de Pharmacie, Hôpital européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris Centre Université-Paris, 20 rue Leblanc, 75015 Paris, France
Damien Lannoy
CHU Lille, Institut de Pharmacie, F-59000 Lille, France
Leen Van Simaey
Laboratory Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent University, C. Heymanslaan 10, B-9000 Gent, Belgium
Hans Duyvejonck
Laboratory Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent University, C. Heymanslaan 10, B-9000 Gent, Belgium
Romain Guillemain
Service d’Anesthésie-Réanimation, Hôpital Européen Georges Pompidou, 75015 Paris, France
Caroline Thumerelle
Pediatric Pulmonology and Allergy Unit, Hôpital Jeanne de Flandre, University Lille, CHU Lille, F-59000 Lille, France
Isabelle Podglajen
Université de Paris, F-75006 Paris, France
Fabrice Compain
Université de Paris, F-75006 Paris, France
Najiby Kassis
Unité d'Hygiène Hospitalière, Service de Microbiologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France
Jean-Luc Mainardi
Université de Paris, F-75006 Paris, France
Johannes Wittmann
Leibniz Institute DSMZ—German Collection of Microorganisms and Cell Cultures GmbH, Inhoffenstraße 7B, 38124 Braunschweig, Germany
Christine Rohde
Leibniz Institute DSMZ—German Collection of Microorganisms and Cell Cultures GmbH, Inhoffenstraße 7B, 38124 Braunschweig, Germany
Jean-Paul Pirnay
Laboratory Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, B-1120 Brussels, Belgium
Nicolas Dufour
Service de Réanimation Médico-Chirurgicale, Centre Hospitalier René Dubos, 95300 Pontoise, France
Stefan Vermeulen
Research Center Health & Water Technology, University College Ghent, Keramiekstraat 80, B-9000 Gent, Belgium
Yannick Gansemans
Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Gent, Belgium
Filip Van Nieuwerburgh
Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Gent, Belgium
Mario Vaneechoutte
Laboratory Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent University, C. Heymanslaan 10, B-9000 Gent, Belgium
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.