Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.
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Dedrick Rebekah M, Smith Bailey E, Cristinziano Madison, Freeman Krista G, Jacobs-Sera Deborah, Belessis Yvonne, Whitney Brown A, Cohen Keira A, Davidson Rebecca M, van Duin David, Gainey Andrew, Garcia Cristina Berastegui, Robert George C R, Haidar Ghady, Ip Winnie, Iredell Jonathan, Khatami Ameneh, Little Jessica S, Malmivaara Kirsi, McMullan Brendan J, Michalik David E, Moscatelli Andrea, Nick Jerry A, Tupayachi Ortiz Maria G, Polenakovik Hari M, Robinson Paul D, Skurnik Mikael, Solomon Daniel A, Soothill James, Spencer Helen, Wark Peter, Worth Austen, Schooley Robert T, Benson Constance A, Hatfull Graham F
Аннотация
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.