Toward Modern Inhalational Bacteriophage Therapy: Nebulization of Bacteriophages of Burkholderia cepacia Complex
Toward Modern Inhalational Bacteriophage Therapy: Nebulization of Bacteriophages of Burkholderia cepacia Complex
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DOI：
10.1089/jamp.2008.0701
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发表时间：
2008-12-01
影响因子：
3.4
通讯作者：
Finlay, Warren. H.
中科院分区：
文献类型：
--
作者：
Golshahi, Laleh;Seed, Kimberley D.;Finlay, Warren. H.
抗生素耐药性细菌感染重新引起了人们对寻找替代治疗方法的兴趣。本体外研究的目的是研究通过雾化气雾剂给药呼吸递送洋葱伯克霍尔德菌复合体（BCC）噬菌体的可能性。用Pari LC星星和eFlow雾化器雾化等渗盐水中的噬菌体，滴度平均值（标准差）为2.15 x 10（8）（1.63 x 10（8））空斑形成单位（PFU）/mL（2.5 mL雾化器填充量）。使用肺波形发生器模拟成人的呼吸模式。在呼吸模拟过程中，使用相位多普勒风速仪（PDA）测量雾化气溶胶的粒径分布。随后通过在低阻力过滤器上收集气溶胶并测量噬菌体滴度来确定雾化器递送的效率。这些过滤器滴度用作数学肺沉积模型的输入数据，以预测肺中噬菌体的区域沉积和每个传导气道生成的液体表面层中的初始噬菌体滴度。结果表明，BCC噬菌体可以在合理的递送时间内成功雾化，并且肺中的预测滴度表明该方法可能具有治疗囊性纤维化患者中常见的细菌性肺部感染的潜力。
Antibiotic-resistant bacterial infections have renewed interest in finding substitute methods of treatment. The purpose of the present in vitro Study was to investigate the possibility of respiratory delivery of a Burkholderia cepacia complex (BCC) bacteriophage by nebulized aerosol administration. Bacteriophages in isotonic saline were aerosolized with Pari LC star and eFlow nebulizers, at titers with mean value (standard deviation) of 2.15 x 10(8) (1.63 x 10(8)) plaque-forming unit (PFU)/mL in 2.5-mL nebulizer fills. The breathing pattern of an adult was simulated using a pulmonary waveform generator. During breath simulation, the size distributions of the nebulized aerosol were measured using phase doppler anemometry (PDA). Efficiency of nebulizer delivery was subsequently determined by collection of aerosol on low resistance filters and measurement of bacteriophage titers. These filter titers were used as input data to a mathematical lung deposition model to predict regional deposition of bacteriophages in the lung and initial bacteriophage titers in the liquid Surface layer of each conducting airway generation. The results suggest that BCC bacteriophages can be nebulized successfully within a reasonable delivery time and predicted titers in the lung indicate that this method may hold potential for treatment of bacterial lung infections common among cystic fibrosis patients.