Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.
Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.
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DOI：
10.1093/cid/ciac453
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发表时间：
2023-01-06
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--
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中科院分区：
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非结核分枝杆菌感染，特别是结核分枝杆菌，在囊性纤维化和慢性支气管扩张性肺病患者中越来越常见。由于固有的抗生素耐药性，治疗具有挑战性。噬菌体疗法代表了一种潜在的新方法。可利用的活性裂解酶相对较少，并且M.需要个性化的噬菌体鉴定。 从200个培养阳性的有症状的疾病患者的分枝杆菌分离株筛选噬菌体亲和性。55个分离株鉴定出一个或多个裂解酶。在同情使用的基础上，对20例患者静脉内、雾化或两者给予噬菌体，并监测患者的不良反应、临床和微生物学反应、噬菌体耐药性的出现以及血清、痰液或支气管肺泡灌洗液中的噬菌体中和。在任何患者中均未观察到归因于治疗的不良反应，无论病原体、给药途径或给药途径如何。在11例患者中观察到有利的临床或微生物学反应。在8名患者中开始静脉内噬菌体递送后，在血清中鉴定出中和抗体，这可能导致4例患者缺乏治疗反应，但在其他患者中与不利反应并不一致。11名患者仅用单一噬菌体治疗，并且在这些患者中没有观察到噬菌体抗性。由于治疗上有用的抗生素有限，分枝杆菌感染的噬菌体治疗具有挑战性，但缺乏任何其他治疗选择的患者的有利临床结果支持继续开发用于某些分枝杆菌感染的噬菌体治疗。我们描述了20例连续的噬菌体治疗分枝杆菌感染。我们没有观察到不良反应，至少50%的患者预后良好，没有噬菌体耐药性的证据，中和免疫反应与治疗成功无关。
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. 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. 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. 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. We describe 20 consecutive cases of bacteriophage treatment of Mycobacterium infections. We observed no adverse reactions, favorable outcomes in at least 50% of patients, no evidence of phage resistance, and neutralizing immune reactions that do not correlate with treatment success.
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影响因子：
6.4
作者：
Guerrero-Bustamante CA;Dedrick RM;Garlena RA;Russell DA;Hatfull GF
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影响因子：
82.9
作者：
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通讯作者：
Spencer, Helen