Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China.

Fu LI; Gui Lian LI; Hui Pang; Hai Can Liu; Tong Yang Xiao; Shuang Jun LI; Qiao Luo; Yi Jiang; Rui Bai Wang; Kang Lin Wan

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Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China.

Author: Fu LI ¹ ; Gui Lian LI ¹ ; Hui PANG ^{2
,

3} ; Hai Can LIU ¹ ; Tong Yang XIAO ¹ ; Shuang Jun LI ^{2
,

4} ; Qiao LUO ^{2
,

4} ; Yi JIANG ¹ ; Rui Bai WANG ¹ ; Kang Lin WAN ¹
Author Information

1. State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
2. State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
3. Immunology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China.
4. Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Publication Type:Journal Article
Keywords: Drug resistance; Macrolide; Non-tuberculous mycobacteria
MeSH: Anti-Bacterial Agents; pharmacology; Bacterial Proteins; genetics; metabolism; China; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Macrolides; pharmacology; Mycobacterium; drug effects; genetics; Polymorphism, Genetic
From: Biomedical and Environmental Sciences 2018;31(4):290-299
CountryChina
Language:English
Abstract:
OBJECTIVEMacrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China.
METHODSFour macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm, were analyzed with nucleotide sequence analysis.
RESULTSVaried effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae. The genes erm(39) and erm(41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar.
CONCLUSIONThe susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.