Activity of Oritavancin and Its Synergy with Other Antibiotics against Mycobacterium abscessus Infection In Vitro and In Vivo |
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| Authors: | Gaoyan Wang Jia Tang Jiajia Feng Wenqi Dong Xinyu Huo Hao Lu Chenchen Wang Wenjia Lu Xiangru Wang Huanchun Chen Chen Tan |
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| Affiliation: | 1.State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (G.W.); (J.T.); (J.F.); (W.D.); (X.H.); (H.L.); (C.W.); (W.L.); (X.W.); (H.C.);2.Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China;3.International Research Center for Animal Disease, Ministry of Science and Technology of the People’s Republic of China, Wuhan 430070, China |
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| Abstract: | Background: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. Methods: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time–kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. Results: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. Conclusions: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection. |
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| Keywords: | Mycobacterium abscessus oritavancin synergy immunosuppressive mice model |
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