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

Efficacy of phikm18p phage therapy in a murine model of extensively drug-resistant Acinetobacter baumannii infection Jiun-Ling Wang,1,* Chih-Feng Kuo,2,* Che-Ming Yeh,3 Jung-Ren Chen,4 Ming-Fang Cheng,5–7 Chih-Hsin Hung3 1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; 2Department of Nursing, I-Shou University, Kaohsiung, Taiwan, ROC; 3Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan, ROC; 4Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan, ROC; 5Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; 6School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; 7Department of Nursing, Fooyin University, Kaohsiung, Taiwan, ROC *These authors contributed equally to this work 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 methods: We studied ϕkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia. 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. 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. Keywords: Acinetobacter baumannii, survival rates, bacteria, multiple antimicrobial drug resistance, phage therapy