Efficacy of φkm18p phage therapy in a murine model of extensively drug-resistant Acinetobacter baumannii infection

φkm18p噬菌体疗法对广泛耐药鲍曼不动杆菌感染小鼠模型的疗效

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作者:Jiun-Ling Wang, Chih-Feng Kuo, Che-Ming Yeh, Jung-Ren Chen, Ming-Fang Cheng, Chih-Hsin Hung

Conclusion

Phage therapy in XDRAB bacteremia increased the animal survival rates, decreased the bacteremia loads, and decreased the levels of inflammatory markers TNF-α and IL-6. However, the reduced therapeutic effect with delayed administrations may be a concern in developing a successful phage therapy for treating acute infections of multidrug-resistant pathogens.

Methods

We studied φkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia.

Purpose

Few effective antibiotics are available for treating extensively drug-resistant Acinetobacter baumannii (XDRAB) sepsis. Phage therapy may show potential in treating XDRAB infections. Materials and

Results

We observed survival rates of nearly 100% in groups given phage therapy concurrent with XDRAB at different multiplicities of infection. In mice that received phage therapy after a 1-hour delay, the survival rate decreased to about 50%. The bacterial load in the blood decreased from 108 to 102 and 103 colony-forming units (CFU)/mL in the concurrent treatment group. In the phage therapy group, the levels of the cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), were low at 3 hours after infection. Although some phage-resistant mutants were isolated after phage therapy, a cytotoxicity study showed that they had reduced fitness.

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