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

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2018
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Abstract
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
Reference Key
jiunling2018efficacyinfection Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Jiun-Ling Wang;Chih-Feng Kuo;Che-Ming Yeh;Jung-Ren Chen;Ming-Fang Cheng;Chih-Hsin Hung and
Journal Infection and drug resistance
Year 2018
DOI
10.2147/IDR.S179701
URL
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