Wang Jiun-Ling, Kuo Chih-Feng, Yeh Che-Ming, Chen Jung-Ren, Cheng Ming-Fang, Hung Chih-Hsin
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Department of Nursing, I-Shou University, Kaohsiung, Taiwan, ROC.
Infect Drug Resist. 2018 Nov 15;11:2301-2310. doi: 10.2147/IDR.S179701. eCollection 2018.
Few effective antibiotics are available for treating extensively drug-resistant (XDRAB) sepsis. Phage therapy may show potential in treating XDRAB infections.
We studied φkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia.
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 10 to 10 and 10 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.
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.
治疗广泛耐药鲍曼不动杆菌（XDRAB）败血症的有效抗生素很少。噬菌体疗法可能在治疗XDRAB感染方面显示出潜力。
我们在XDRAB菌血症的BALB/c和C57BL/6小鼠模型中研究了φkm18p噬菌体疗法。
我们观察到在不同感染复数下同时给予噬菌体疗法和XDRAB的组中存活率接近100%。在延迟1小时后接受噬菌体疗法的小鼠中，存活率降至约50%。同时治疗组血液中的细菌载量从10⁷降至10⁵和10⁴菌落形成单位（CFU）/mL。在噬菌体疗法组中，感染后3小时肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）等细胞因子水平较低。尽管在噬菌体疗法后分离出了一些噬菌体抗性突变体，但细胞毒性研究表明它们的适应性降低。
XDRAB菌血症的噬菌体疗法提高了动物存活率，降低了菌血症载量，并降低了炎症标志物TNF-α和IL-6的水平。然而，延迟给药导致治疗效果降低可能是开发成功的噬菌体疗法治疗多重耐药病原体急性感染时需要关注的问题。
