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Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter

机译:吸入噬菌体治疗多重耐药无色杆菌

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摘要

The rise of antimicrobial resistant (AMR) bacteria is a global public health threat. AMR Achromobacter bacteria pose a challenging clinical problem, particularly for those with cystic fibrosis (CF) who are predisposed to chronic bacterial lung infections. Lytic bacteriophages (phages) offer a potential alternative to treat AMR infections, with the possible benefit that phage selection for resistance in target bacteria might coincide with reduced pathogenicity. The result is a genetic “trade-off,” such as increased sensitivity to chemical antibiotics, and/or decreased virulence of surviving bacteria that are phage resistant. Here, we show that two newly discovered lytic phages against Achromobacter were associated with stabilization of respiratory status when deployed to treat a chronic pulmonary infection in a CF patient using inhaled (nebulized) phage therapy. The two phages demonstrate traits that could be generally useful in their development as therapeutics, especially the possibility that the phages can select for clinically useful trade-offs if bacteria evolve phage resistance following therapy. We discuss the limitations of the current study and suggest further work that should explore whether the phages could be generally useful in targeting pulmonary or other Achromobacter infections in CF patients.
机译:抗菌素耐药性 (AMR) 细菌的兴起是一个全球性的公共卫生威胁。抗菌素耐药性无色杆菌是一个具有挑战性的临床问题,特别是对于易患慢性细菌性肺部感染的囊性纤维化 (CF) 患者。裂解噬菌体(噬菌体)为治疗 AMR 感染提供了一种潜在的替代方案,其可能的好处是,靶细菌耐药性的噬菌体选择可能与致病性降低相吻合。结果是遗传“权衡”,例如对化学抗生素的敏感性增加,和/或噬菌体耐药的存活细菌的毒力降低。在这里,我们表明,当使用吸入(雾化)噬菌体疗法治疗 CF 患者的慢性肺部感染时,两种新发现的针对无色杆菌的裂解噬菌体与呼吸状态的稳定有关。这两种噬菌体表现出通常对其作为治疗剂的开发有用的特性,特别是如果细菌在治疗后产生噬菌体耐药性,噬菌体可以选择临床有用的权衡。我们讨论了当前研究的局限性,并建议进一步开展工作,以探索噬菌体是否通常可用于靶向 CF 患者的肺部或其他无色杆菌感染。

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