1. Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease
- Author
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Rebekah M Dedrick, Bailey E Smith, Madison Cristinziano, Krista G Freeman, Deborah Jacobs-Sera, Yvonne Belessis, A Whitney Brown, Keira A Cohen, Rebecca M Davidson, David van Duin, Andrew Gainey, Cristina Berastegui Garcia, C R Robert George, Ghady Haidar, Winnie Ip, Jonathan Iredell, Ameneh Khatami, Jessica S Little, Kirsi Malmivaara, Brendan J McMullan, David E Michalik, Andrea Moscatelli, Jerry A Nick, Maria G Tupayachi Ortiz, Hari M Polenakovik, Paul D Robinson, Mikael Skurnik, Daniel A Solomon, James Soothill, Helen Spencer, Peter Wark, Austen Worth, Robert T Schooley, Constance A Benson, Graham F Hatfull, Institut Català de la Salut, [Dedrick RM, Smith BE, Cristinziano M, Freeman KG, Jacobs-Sera D] Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. [Belessis Y] School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia. Department of Respiratory Medicine, Sydney Children’s Hospital, Sydney, New South Wales, Australia. [Berastegui Garcia C] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Human Microbiome Research, Tutkimusohjelmayksikkö, Mikael Skurnik / Vastuullinen tutkija, HUSLAB, Bakteriologian ja immunologian osasto, and Helsingin yliopisto
- Subjects
Microbiology (medical) ,infecciones bacterianas y micosis::infecciones bacterianas::infecciones por bacterias grampositivas::infecciones por Actinomycetales::micobacteriosis::infecciones por micobacterias no tuberculosas [ENFERMEDADES] ,Phage therapy ,Mycobacteriophage ,Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Actinomycetales Infections::Mycobacterium Infections::Mycobacterium Infections, Nontuberculous [DISEASES] ,Other subheadings::/therapy [Other subheadings] ,Bacteriòfags ,3121 Yleislääketiede, sisätaudit ja muut kliiniset lääketieteet ,Infectious Diseases ,terapéutica::terapia biológica::terapia fágica [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Medicaments antibacterians - Ús terapèutic ,Therapeutics::Biological Therapy::Phage Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Micobacteriosis - Tractament ,Nontuberculous mycobacteria ,Otros calificadores::/terapia [Otros calificadores] - Abstract
Background Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.
- Published
- 2023