Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease

作者：Rebekah M. Dedrick, Bailey E. Smith, Madison Cristinziano, Krista G. Freeman, Deborah Jacobs‐Sera, Yvonne Belessis, Anne Brown, Keira A. Cohen, Rebecca M. Davidson, David van Duin, Andrew B. Gainey, Cristina Berastegui, C. R. Robert George, Ghady Haidar, Winnie Ip, Jonathan R. Iredell, Ameneh Khatami, Jessica S Little, Kirsi Malmivaara, Brendan McMullan, David E. Michalik, Andrea Moscatelli, Jerry A. Nick, Maria Gabriela Tupayachi Ortiz, Hari Polenakovik, Paul D. Robinson, Mikael Skurnik, Daniel A. Solomon, J F Soothill, Helen Spencer, Peter Wark, Austen Worth, Robert T. Schooley, Constance A. Benson, Graham F. Hatfull · 发表于：Clinical Infectious Diseases · 年份：2022 · DOI：10.1093/cid/ciac453 · 被引用次数：346 · 研究领域：Bacteriophages and microbial interactions、Mycobacterium research and diagnosis、Tuberculosis Research and Epidemiology

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 patien...