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)

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[2]	ZHOU Wen-qiang, ZHANG Shuang, CHU Nai-hui. Current status and prospect of all-oral treatment regimens for drug-resistant pulmonary tuberculosis [J]. Chinese Journal of Antituberculosis, 2021, 43(9): 879-882.
[3]	DING Cai-hong, XIONG Yu, WANG Qing, GAO Xu-sheng, HAO Yan. Study on the early efficacy and safety of the regimen containing bedaquiline in the treatment of multidrug-resistant pulmonary tuberculosis [J]. Chinese Journal of Antituberculosis, 2021, 43(9): 893-898.
[4]	SHI Wen-hui, CHU Nai-hui. Resistance to fluoroquinolones and the influencing factors in patients with drug-resistant pulmonary tuberculosis [J]. Chinese Journal of Antituberculosis, 2021, 43(9): 905-909.
[5]	LIN Jian, LIN Shu-fang, DAI Zhi-song, ZHAO Yong, ZHOU Yin-fa, ZHANG Tian-lin, WEI Shu-zhen. Analysis of the drug resistance surveillance results of Mycobacterium tuberculosis in Fujian Province from 2016 to 2019 [J]. Chinese Journal of Antituberculosis, 2021, 43(9): 924-928.
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[14]	YANG Ting-ting, GAO Qian. The tuberculosis drug-resistance and transmission surveillance network based on whole genome sequencing data [J]. Chinese Journal of Antituberculosis, 2021, 43(7): 645-648.
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