{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:29:56Z","timestamp":1790522996542,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key R&amp;D Program of China","award":["2017YFD0500303"],"award-info":[{"award-number":["2017YFD0500303"]}]},{"name":"the outstanding youth project of Natural Science Foundation in Hubei Province","award":["2019CFA095"],"award-info":[{"award-number":["2019CFA095"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013kill 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.<\/jats:p>","DOI":"10.3390\/ijms22126346","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T10:30:25Z","timestamp":1623666625000},"page":"6346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Activity of Oritavancin and Its Synergy with Other Antibiotics against Mycobacterium abscessus Infection In Vitro and In Vivo"],"prefix":"10.3390","volume":"22","author":[{"given":"Gaoyan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Huo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjia","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-1378","authenticated-orcid":false,"given":"Xiangru","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1164\/rccm.201003-0503OC","article-title":"Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: An emerging public health disease","volume":"182","author":"Winthrop","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/jid.1953.18","article-title":"An unusual acid-fast infection of the knee with subcutaneous, abscess-like lesions of the gluteal region; report of a case with a study of the organism, Mycobacterium abscessus, n. sp.","volume":"20","author":"Moore","year":"1953","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.healun.2006.04.003","article-title":"Mycobacterium abscessus chest wall and pulmonary infection in a cystic fibrosis lung transplant recipient","volume":"25","author":"Taylor","year":"2006","journal-title":"J. Heart Lung Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1126\/science.aaf8156","article-title":"Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium","volume":"354","author":"Bryant","year":"2016","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.drudis.2018.04.001","article-title":"NTM drug discovery: Status, gaps and the way forward","volume":"23","author":"Wu","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41579-020-0331-1","article-title":"Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus","volume":"18","author":"Johansen","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1164\/rccm.200604-571ST","article-title":"An official ATS\/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases","volume":"175","author":"Griffith","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1136\/thoraxjnl-2015-207360","article-title":"US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis","volume":"71","author":"Floto","year":"2016","journal-title":"Thorax"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1093\/cid\/ciz071","article-title":"Mycobacterium abscessus and Antibiotic Resistance: Same As It Ever Was","volume":"69","author":"Griffith","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41591-019-0437-z","article-title":"Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus","volume":"25","author":"Dedrick","year":"2019","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciaa241","article-title":"Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS\/ERS\/ESCMID\/IDSA Clinical Practice Guideline: Executive Summary","volume":"71","author":"Daley","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Egorova, A., Jackson, M., Gavrilyuk, V., and Makarov, V. (2021). Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities. Med. Res. Rev.","DOI":"10.1002\/med.21798"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mukherjee, D., Wu, M.L., Teo, J.W.P., and Dick, T. (2017). Vancomycin and Clarithromycin Show Synergy against Mycobacterium abscessus In Vitro. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.01298-17"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chew, K.L., Octavia, S., Go, J., Ng, S., Tang, Y.E., Soh, P., Yong, J., Jureen, R., Lin, R.T.P., and Yeoh, S.F. (2020). In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens. J. Antimicrob. Chemother.","DOI":"10.1093\/jac\/dkaa520"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sarathy, J.P., Ganapathy, U.S., Zimmerman, M.D., Dartois, V., Gengenbacher, M., and Dick, T. (2020). TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessus. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.02404-19"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nrd3267","article-title":"The antibiotics market","volume":"9","author":"Hamad","year":"2010","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"O297","DOI":"10.1111\/1469-0691.12405","article-title":"In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex","volume":"20","author":"Lavollay","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kwak, N., Dalcolmo, M.P., Daley, C.L., Eather, G., Gayoso, R., Hasegawa, N., Jhun, B.W., Koh, W.J., Namkoong, H., and Park, J. (2019). M ycobacterium abscessus pulmonary disease: Individual patient data meta-analysis. Eur. Respir. J., 54.","DOI":"10.1183\/13993003.01991-2018"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hanh, B.T.B., Kim, T.H., Park, J.W., Lee, D.G., Kim, J.S., Du, Y.E., Yang, C.S., Oh, D.C., and Jang, J. (2020). Etamycin as a Novel Mycobacterium abscessus Inhibitor. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186908"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1093\/jac\/dkn358","article-title":"Comparison of oritavancin versus vancomycin as treatments for clindamycin-induced Clostridium difficile PCR ribotype 027 infection in a human gut model","volume":"62","author":"Baines","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/BF01967563","article-title":"Structure, biochemistry and mechanism of action of glycopeptide antibiotics","volume":"8","author":"Reynolds","year":"1989","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1128\/AAC.00176-15","article-title":"Population pharmacokinetic analysis for a single 1,200-milligram dose of oritavancin using data from two pivotal phase 3 clinical trials","volume":"59","author":"Rubino","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1056\/NEJMoa1310422","article-title":"Single-dose oritavancin in the treatment of acute bacterial skin infections","volume":"370","author":"Corey","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_24","unstructured":"Wilcox Mark, H., Baines, S., Lehoux, D., and Parr Thomas, R. (2013). Method of Inhibiting Clostridium Difficile BY Administration of Oritavancin. (No. 8,518,873), U.S. Patent."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1128\/AAC.46.8.2720-2722.2002","article-title":"Resazurin microtiter assay plate: Simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis","volume":"46","author":"Palomino","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1093\/jac\/dkq374","article-title":"Time-kill kinetics of anti-tuberculosis drugs, and emergence of resistance, in relation to metabolic activity of Mycobacterium tuberculosis","volume":"65","author":"Verbrugh","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ijantimicag.2014.09.012","article-title":"In vitro synergistic activity of clofazimine and other antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis isolates","volume":"45","author":"Zhang","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Maggioncalda, E.C., Story-Roller, E., Ammerman, N.C., Nuermberger, E.L., and Lamichhane, G. (2018). Progressive Mycobacterium abscessus lung infection in C3HeB\/FeJ mice associated with corticosteroid administration. bioRxiv.","DOI":"10.1101\/418491"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/infdis\/jit614","article-title":"In vivo evaluation of antibiotic activity against Mycobacterium abscessus","volume":"209","author":"Lerat","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Story-Roller, E., Maggioncalda, E.C., and Lamichhane, G. (2019). Synergistic Efficacy of beta-Lactam Combinations against Mycobacterium abscessus Pulmonary Infection in Mice. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.00614-19"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Martins, T.G., Trigo, G., Fraga, A.G., Gama, J.B., Longatto-Filho, A., Saraiva, M., Silva, M.T., Castro, A.G., and Pedrosa, J. (2012). Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001925"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hagihara, M., Kato, H., Sugano, T., Okade, H., Sato, N., Shibata, Y., Sakanashi, D., Asai, N., Koizumi, Y., and Suematsu, H. (2021). Pharmacodynamic evaluation of meropenem, cefepime, or aztreonam combined with a novel \u03b2-lactamase inhibitor, nacubactam, against carbapenem-resistant and\/or carbapenemase-producing Klebsiella pneumoniae and Escherichia coli using a murine thigh-infection model. Int. J. Antimicrob. Agents, 57.","DOI":"10.1016\/j.ijantimicag.2021.106330"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1128\/AAC.47.5.1700-1706.2003","article-title":"Pharmacodynamics of oritavancin (LY333328) in a neutropenic-mouse thigh model of Staphylococcus aureus infection","volume":"47","author":"Boylan","year":"2003","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:14:01Z","timestamp":1760163241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,14]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22126346"],"URL":"https:\/\/doi.org\/10.3390\/ijms22126346","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,14]]}}}