上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2021 , Vol. 41 >Issue 9: 1272 - 1276

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.09.022

短篇论著

噬菌体治疗泛耐药肺炎克雷伯菌肺部感染的临床应用及效果初探

  • 李莉莎 ,
  • 李建辉 ,
  • 何斌 ,
  • 吴楠楠 ,
  • 朱同玉 ,
  • 郭晓奎 ,
  • 陈峥宏
展开
  • 1.贵州医科大学基础医学院微生物学教研室，贵阳 550025
    2.上海市公共卫生临床中心，上海噬菌体研究所，上海 201508
    3.上海交通大学医学院国家热带病研究中心全球健康学院，上海 200025
李莉莎（1993—），女，硕士生；电子信箱：xiaxiaday@hotmail.com。
陈峥宏，电子信箱：chenzhenghong@gmc.edu.cn。

收稿日期: 2021-03-10

  网络出版日期: 2021-08-24

基金资助

上海市自然科学基金(17ZR1415900)

收起

Clinical application and effect of phage on the treatment of pulmonary infection by pan-drug resistant Klebsiella pneumoniae

  • Li-sha LI ,
  • Jian-hui LI ,
  • Bin HE ,
  • Nan-nan WU ,
  • Tong-yu ZHU ,
  • Xiao-kui GUO ,
  • Zheng-hong CHEN
Expand
  • 1.Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Guiyang 550025, China
    2.Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Shanghai 201508, China
    3.School of Global Health of Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
CHEN Zheng-hong, E-mail: chenzhenghong@gmc.edu.cn.

Received date: 2021-03-10

  Online published: 2021-08-24

Supported by

Natural Science Foundation of Shanghai(17ZR1415900)

Fold

摘要

目的·探讨使用噬菌体雾化吸入治疗泛耐药肺炎克雷伯菌肺部感染的用药频率及效果。方法·在治疗开始前1 h和使用噬菌体雾化吸入治疗肺部感染过程中每小时，取患者痰液样本进行细菌分离纯化及质谱鉴定，比较细菌裂解谱的异同；同时，于治疗开始前1 h，第一次治疗开始后2、4 h取血液样本进行细菌培养及噬菌体量的测定。结果·噬菌体经雾化吸入后2 h在体内持续增殖，3 h后噬菌体量下降，4 h后进行第二次治疗，噬菌体在体内的增殖规律与第一次相同；第三次使用噬菌体治疗时，噬菌体仅有少量增殖。噬菌体治疗后患者痰液中仍分离到肺炎克雷伯菌，但分离株的噬菌体裂解谱发生了变化，患者临床症状改善。结论·噬菌体能够有效针对靶细菌进行杀灭并改善患者的临床症状。泛耐药肺炎克雷伯菌肺部感染患者经2次雾化吸入治疗即可达到噬菌体使用的最佳效果。噬菌体治疗后病原菌菌株发生了变化。

关键词： 噬菌体; 泛耐药; 肺炎克雷伯菌; 治疗应用

本文引用格式

李莉莎 , 李建辉 , 何斌 , 吴楠楠 , 朱同玉 , 郭晓奎 , 陈峥宏 . 噬菌体治疗泛耐药肺炎克雷伯菌肺部感染的临床应用及效果初探[J]. 上海交通大学学报（医学版）, 2021 , 41(9) : 1272 -1276 . DOI: 10.3969/j.issn.1674-8115.2021.09.022

Abstract

Objective

·To explore the therapeutic frequency and effect of phage treatment on pan-drug resistant Klebsiella pneumoniae by aerosolized phage.

Methods

·The patient's sputum was taken 1 h before the start of treatment and every hour during the treatment of pulmonary infection using nebulized inhaled phage. The sputum samples were subjected to bacterial isolation, purification and mass spectrometry identification. The lytic spectrum of different bacterial isolations was compared. And blood samples for bacteria were taken 1 h before the start of the treatment and 2 h and 4 h after the first treatment for bacterial culture and phage volume determination.

Results

·The phage continued to proliferate in vivo for 2 h, and decreased after 3 h. When the second phage treatment was performed after 4 h, the pattern of phage proliferation in vivo was the same as the first time. During the third treatment, the phage was proliferated slightly in vivo. After phage treatment, Klebsiella pneumoniae was still isolated in the patient's sputum. However, the phage cleavage spectrum of the isolations was different, and the patient's clinical symptoms improved.

Conclusion

·Phages can effectively target infectious bacteria and kill them. The clinical symptoms of patient improve. Twice aerosolized phage treatment for the patient with pulmonary infection is enough to achieve the best effect. The isolated bacterial strain is different post phage treatment.

Key words： phage; pan-drug resistant; Klebsiella pneumoniae; therapeutic application

参考文献

1 Cai RP, Wu M, Zhang H, et al. A smooth-type, phage-resistant Klebsiella pneumoniae mutant strain reveals that OmpC is indispensable for infection by phage GH-K3[J]. Appl Environ Microbiol, 2018, 84(21): e01585-e01518.
2 Tomás JM, Benedí VJ, Jofre JT. Identification of the cell surface receptor for FC3-2, FC3-3 and FC3-6 bacteriophages from Klebsiella pneumoniae[J]. FEMS Microbiol Lett, 1987, 41(3): 223-228.
3 Goldfarb T, Sberro H, Weinstock E, et al. BREX is a novel phage resistance system widespread in microbial genomes[J]. EMBO J, 2015, 34(2): 169-183.
4 Leung CYJ, Weitz JS. Modeling the synergistic elimination of bacteria by phage and the innate immune system[J]. J Theor Biol, 2017, 429: 241-252.
5 Malik DJ, Sokolov IJ, Vinner GK, et al. Formulation, stabilisation and encapsulation of bacteriophage for phage therapy[J]. Adv Colloid Interface Sci, 2017, 249: 100-133.
6 Bakhrushina EO, Anurova MN, Aleshkin AV, et al. Development of the composition and pharmacokinetic studies of suppositories with combined substance of bacteriophages[J]. J Drug Deliv Sci Technol, 2020, 59: 101841.
7 D?browska K. Interaction of bacteriophages with the immune system: induction of bacteriophage-specific antibodies[J]. Methods Mol Biol, 2018, 1693: 139-150.
8 Sinha A, Maurice CF. Bacteriophages: uncharacterized and dynamic regulators of the immune system[J]. Mediat Inflamm, 2019, 2019: 3730519.
9 Azam AH, Tanji Y. Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy[J]. Appl Microbiol Biotechnol, 2019, 103(5): 2121-2131.
10 Wright RCT, Friman VP, Smith MCM, et al. Resistance evolution against phage combinations depends on the timing and order of exposure[J]. mBio, 2019, 10(5): e01652-e01619.
11 Oechslin F. Resistance development to bacteriophages occurring during bacteriophage therapy[J]. Viruses, 2018, 10(7): E351.
12 Kumaran D, Taha M, Yi QL, et al. Does treatment order matter? investigating the ability of bacteriophage to augment antibiotic activity against Staphylococcus aureus biofilms[J]. Front Microbiol, 2018, 9: 127.
Options
文章导航

/

〈 〉