Evaluation of in vitro antibacterial effects of 13 antibiotics against rapidly growing mycobacteria

doi:10.3969/j.issn.1000-6621.2021.09.015

Abstract

Abstract:

Objective To evaluate the susceptibility characteristics of clinical isolates of rapidly growing mycobacteria (RGM) to 13 antibiotics. Methods A total of 98 isolates of RGM recruited from Beijing Chest Hospital, Capital Medical University between January 2015 and December 2019 were collected, including 25 Mycobacterium (M.) fortuitum, 70 M.abscessus and 3 M.chelonae. Sensititre RAPMYCO MIC plate was used to determine 13 antibiotics (amikacin, tobramycin, amoxicillin-clavulanic acid, cefoxitin, imipenem, ciprofloxacin, moxifloxacin, clarithromycin, linezolid, minocycline, doxycycline, tigecycline, trimethoprim-sulfamethoxazole) in vitro antibacterial activity against the 98 RGM clinical isolates. Results Among the 13 tested antibiotics, amikacin had the best in vitro antibacterial activity against three RGM clinical isolates tested, the sensitivity rates to M.fortuitum and M.abscessus were 100.0% (25/25) and 90.0% (63/70), respectively. In vitro antibacterial effect of tigecycline on RGM clinical isolates was better than the effects of doxycycline and minocycline, and the sensitivity rates to M.fortuitum and M.abscessus were 100.0% (25/25) and 72.9% (51/70), respectively. Moxifloxacin and ciprofloxacin showed strong antibacterial activity against M.fortuitum, with sensitivity rates of 100.0% (25/25) and 92.0% (23/25), respectively; however, for M.abscessus branches, they had almost no antibacterial activity in vitro, and the drug resistance rate was 95.7% (67/70). In addition, almost all tested RGM clinical isolates were resistant to cefoxitin, doxycycline, linezolid, imipenem, and methoxazole-sulfamethoxazole. Conclusion Amikacin, tigecycline and clarithromycin had good in vitro antimicrobial activity against M.abscessus and M.fortuitum, but there were still differences among different strains. Separate drug sensitivity test is necessary to be carried out for each strain or clinical strain.

Key words: Mycobacteria,atypical, Rapidly growing mycobacteria, Microbial sensitivity tests, Drug resistance, Evaluation studies

YU Xia, REN Ru-yan, WEN Shu-an, LIANG Qian, DONG Ling-ling, HUANG Hai-rong. Evaluation of in vitro antibacterial effects of 13 antibiotics against rapidly growing mycobacteria[J]. Chinese Journal of Antituberculosis, 2021, 43(9): 947-951. doi: 10.3969/j.issn.1000-6621.2021.09.015

Figures/Tables 3

References 14

[1]	Hoefsloot W, van Ingen J, Andrejak C, et al. The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur Respir J, 2013, 42(6):1604-1613. doi: 10.1183/09031936.00149212. doi: 10.1183/09031936.00149212 pmid: 23598956
[2]	Alcaide F, Peña MJ, Pérez-Risco D, et al. Increasing isolation of rapidly growing mycobacteria in a low-incidence setting of environmental mycobacteria, 1994-2015. Eur J Clin Microbiol Infect Dis, 2017, 36(8):1425-1432. doi: 10.1007/s10096-017-2949-0. doi: 10.1007/s10096-017-2949-0 URL
[3]	Duan H, Han X, Wang Q, et al. Clinical Significance of Nontuberculous Mycobacteria Isolated From Respiratory Specimens in a Chinese Tuberculosis Tertiary Care Center. Sci Rep, 2016, 6:36299. doi: 10.1038/srep36299. doi: 10.1038/srep36299 URL
[4]	Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med, 2007, 175(4):367-416. doi: 10.1164/rccm.200604-571ST. doi: 10.1164/rccm.200604-571ST URL
[5]	Kennedy BS, Bedard B, Younge M, et al. Outbreak of Mycobacterium chelonae infection associated with tattoo ink. N Engl J Med, 2012, 367(11):1020-1024. doi: 10.1056/NEJMoa1205114. doi: 10.1056/NEJMoa1205114 URL
[6]	Meyers H, Brown-Elliott BA, Moore D, et al. An outbreak of Mycobacterium chelonae infection following liposuction. Clin Infect Dis, 2002, 34(11):1500-1507. doi: 10.1086/340399. doi: 10.1086/340399 pmid: 12015697
[7]	Li G, Lian LL, Wan L, et al. Antimicrobial susceptibility of standard strains of nontuberculous mycobacteria by microplate Alamar Blue assay. PLoS One, 2013, 8(12):e84065. doi: 10.1371/journal.pone.0084065. doi: 10.1371/journal.pone.0084065 URL
[8]	Yu X, Liu P, Liu G, et al. The prevalence of non-tuberculous mycobacterial infections in mainland China: Systematic review and meta-analysis. J Infect, 2016, 73(6):558-567. doi: 10.1016/j.jinf.2016.08.020. doi: 10.1016/j.jinf.2016.08.020 URL
[9]	Cavusoglu C, Gurpinar T, Ecemis T. Evaluation of antimicrobial susceptibilities of rapidly growing mycobacteria by Sensititre RAPMYCO panel. New Microbiol, 2012, 35(1):73-76. pmid: 22378556
[10]	Clinical and Laboratory Standards Institute. Clinical and laboratory standards institute. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes. Annapolis Junction: Clinical and Laboratory Stan-dards Institute, 2011.
[11]	Lee MR, Ko JC, Liang SK, et al. Bacteraemia caused by Mycobacterium abscessus subsp. abscessus and M.abscessus subsp. bolletii: clinical features and susceptibilities of the isolates. Int J Antimicrob Agents, 2014, 43(5):438-441. doi: 10.1016/j.ijantimicag.2014.02.007. doi: 10.1016/j.ijantimicag.2014.02.007 URL
[12]	Tang SS, Lye DC, Jureen R, et al. Rapidly growing mycobacteria in Singapore, 2006—2011. Clin Microbiol Infect, 2015, 21(3):236-241. doi: 10.1016/j.cmi.2014.10.018. doi: 10.1016/j.cmi.2014.10.018 URL
[13]	Hatakeyama S, Ohama Y, Okazaki M, et al. Antimicrobial susceptibility testing of rapidly growing mycobacteria isolated in Japan. BMC Infect Dis, 2017, 17(1):197. doi: 10.1186/s12879-017-2298-8. doi: 10.1186/s12879-017-2298-8 pmid: 28270102
[14]	陈品儒, 蔡杏珊, 肖芃, 等. 致病性速生型非结核分枝杆菌 MIC 法检测及药敏结果分析. 广东医学, 2012, 33(23):3620-3623. doi: 10.3969/j.issn.1001-9448.2012.23.046. doi: 10.3969/j.issn.1001-9448.2012.23.046

药品	龟分枝杆菌 (ATCC14472)	偶发分枝杆菌 (ATCC6481)	脓肿分枝杆菌 (ATCC19977)
阿米卡星	32	1	8
妥布霉素	>8	1	>8
阿莫西林- 克拉维酸	>64/32	>4/32	>64/32
头孢西丁	128	32	>128
亚胺培南	>64	16	>64
环丙沙星	>4	0.5	>4
莫西沙星	8	0.25	>8
克拉霉素	16	4	0.12
利奈唑胺	32	>32	32
米诺环素	>8	1	>8
多西霉素	>16	0.5	>16
替加环素	1	0.12	1
甲氧苄啶- 磺胺甲噁唑	>8/152	8/152	>8/152

药品	MIC 临界浓度(μg/ml)^a			偶发分枝杆菌(25株)
药品	敏感	临界浓度	耐药	MIC范围 (μg/ml)	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	敏感菌株[株 (敏感率,%)]
阿米卡星	≤16	32	≥64	1~2	1	1	25(100.0)
妥布霉素	≤2	4	≥8	4~>16	16	>16	0(0.0)
阿莫西林-克拉维酸	-	-	-	64/32	64/32	64/32	-
头孢西丁	≤16	32~64	≥128	64~>128	64	128	0(0.0)
亚胺培南	≤4	8~16	≥32	32~>64	>64	>64	0(0.0)
环丙沙星	≤1	2	≥4	0.12~4	0.12	0.25	23(92.0)
莫西沙星	≤1	2	≥4	0.25~0.5	0.25	0.25	25(100.0)
克拉霉素	≤2	4	≥8	1~>16	>16	>16	1(4.0)
利奈唑胺	≤8	16	≥32	8~>32	32	>32	1(4.0)
米诺环素	≤1	2~4	≥8	1~>8	>8	>8	2(8.0)
多西霉素	≤1	2~4	≥8	0.25~>16	>16	>16	3(12.0)
替加环素^b	-	-	-	0.12~1	0.25	0.25	25(100.0)
甲氧苄啶-磺胺甲噁唑	≤2/38	-	≥4/76	1/19-4/76	4/76	4/76	5(20.0)

药品	MIC 临界浓度(μg/ml)^a			脓肿分枝杆菌(70株)
药品	敏感	临界浓度	耐药	MIC范围 (μg/ml)	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	敏感菌株[株 (敏感率,%)]
阿米卡星	≤16	32	≥64	1~32	16	16	63(90.0)
妥布霉素	≤2	4	≥8	2~>16	16	>16	1(1.4)
阿莫西林-克拉维酸	-	-	-	64/32~>64/32	64/32	>64/32	-
头孢西丁	≤16	32~64	≥128	16~>128	128	>128	1(1.4)
亚胺培南	≤4	8~16	≥32	8~>64	>64	>64	0(0.0)
环丙沙星	≤1	2	≥4	0.12~>4	>4	>4	3(4.3)
莫西沙星	≤1	2	≥4	2~>8	>8	>8	3(4.3)
克拉霉素	≤2	4	≥8	0.06~>16	1	16	43(61.4)
利奈唑胺	≤8	16	≥32	2~>32	32	>32	2(2.9)
米诺环素	≤1	2~4	≥8	1~>8	>8	>8	2(2.9)
多西霉素	≤1	2~4	≥8	0.12~>16	>16	>16	2(2.9)
替加环素^b	-	-	-	0.06~>4	1	4	51(72.9)
甲氧苄啶-磺胺甲噁唑	≤2/38	-	≥4/76	0.25/4.75~8/152	>8/152	>8/152	3(4.3)

[1]	Li Yuhong, Mei Jinzhou, Su Wei, Ruan Yunzhou, Liu Yushu, Zhao Yanlin, Liu Xiaoqiu. Analysis of the treatment outcomes and influencing factors of rifampicin-resistant pulmonary tuberculosis patients aged 65 and above in China from 2015 to 2021 [J]. Chinese Journal of Antituberculosis, 2025, 47(4): 408-415.
[2]	Yang Ziyi, Chen Suting. Research progress on bedaquiline resistance and drug resistance diagnosis [J]. Chinese Journal of Antituberculosis, 2025, 47(3): 374-379.
[3]	Li Xuelian, Zhang Hongyan, Wang Jun, Wang Qingfeng, Ma Liping, Chu Naihui, Nie Wenjuan. Safety of extended delamanid use in drug-resistant tuberculosis patients [J]. Chinese Journal of Antituberculosis, 2025, 47(2): 164-168.
[4]	Yan Guangxuan, Wang Xueyu, Wang Yujin, Lan Tinglong, Nie Wenjuan. Diagnostic value of using metagenomic second-generation sequencing on suspected osteoarticular tuberculosis patients [J]. Chinese Journal of Antituberculosis, 2025, 47(2): 175-180.
[5]	Xu Zian, Pu Feifei, Feng Jing, Xia Ping. Research progress of high-throughput sequencing technology in the diagnosis and treatment of osteoarticular tuberculosis [J]. Chinese Journal of Antituberculosis, 2025, 47(2): 224-230.
[6]	Chen Jifei, Huang Lihua, Luo Lanbo, Sui Wenxian, Pang Yu, Liu Aimei. Evaluation the efficacy of tongue swab-based PCR fluorescence probe method for pulmonary tuberculosis [J]. Chinese Journal of Antituberculosis, 2025, 47(1): 51-60.
[7]	Geng Zimei, Wang Chaohong, Long Sibo, Zheng Maike, Shi Yiheng, Sun Yong, Zhao Yan, Wang Guirong. Analysis of bacteriological positivity and rifampicin resistance in patients with severe pulmonary tuberculosis [J]. Chinese Journal of Antituberculosis, 2024, 46(9): 1050-1055.
[8]	Chen Shuangshuang, Tian Lili, Wang Nenhan, Yang Xinyu, Zhao Yanfeng, Li Chuanyou, Dai Xiaowei. Analysis of in vitro antibacterial effects of 17 antibiotics against rapidly growing mycobacteria in the Beijing area [J]. Chinese Journal of Antituberculosis, 2024, 46(9): 1056-1062.
[9]	Wang Fei, Hua Duo, Guo Jianjian, Liu Chang, Han Lu, Ren Yi. Characteristic analysis of non-tuberculous mycobacterial pulmonary disease patients in Wuhan area from 2021 to 2023 [J]. Chinese Journal of Antituberculosis, 2024, 46(9): 1069-1076.
[10]	Wang Biao, Liu Yuhong, Sun Yuxian, Zhang Lijie, Li Zhili, Shu Wei. Investigation and analysis of laboratory diagnostic capabilities in tuberculosis-designated hospitals in China [J]. Chinese Journal of Antituberculosis, 2024, 46(9): 1089-1097.
[11]	Yang Liangzi, Zhang Peize, Lu Shuihua. Interpretation of World Health Organization’s Co-administration of Treatment for Drug-resistant Tuberculosis and Hepatitis C: 2024 Update [J]. Chinese Journal of Antituberculosis, 2024, 46(8): 874-876.
[12]	Xue Yi, Liang Qian, Qi Haoran, Liang Ruixia, Huang Hairong. Reliability analysis of rifampicin-resistance detected by different diagnostics as a predictor for multidrug-resistant tuberculosis [J]. Chinese Journal of Antituberculosis, 2024, 46(8): 892-896.
[13]	Yu Lan, Chen Shuangshuang, Wang Nenhan, Tian Lili, Zhao Yanfeng, Fan Ruifang, Liu Haican, Li Chuanyou, Dai Xiaowei. Consistency between phenotypic resistance to fluoroquinolones and genetic mutations in rifampicin resistant Mycobacterium tuberculosis strains [J]. Chinese Journal of Antituberculosis, 2024, 46(8): 942-950.
[14]	Gao Lei, Liang Yaxue, Liu Shengsheng, Wang Hua. Analysis of treatment outcomes and influencing factors in 144 elderly patients with rifampicin drug-resistant pulmonary tuberculosis [J]. Chinese Journal of Antituberculosis, 2024, 46(7): 799-807.
[15]	Zhang Hongtai, Ren Yixuan, Hu peilei, Wang Nenhan, Li Jie, Tian Lili, Zhao Yanfeng, Chen Shuangshuang, Li Chuanyou. Comparison of microbiota diversity in the sputum of pulmonary tuberculosis patients with rifampicin resistance or sensitivity [J]. Chinese Journal of Antituberculosis, 2024, 46(6): 625-633.