Skip to main content
Emerging Infectious Diseases logoLink to Emerging Infectious Diseases
letter
. 2014 Jul;20(7):1252–1253. doi: 10.3201/eid2007.131801

Prevalence and Drug Resistance of Nontuberculous Mycobacteria, Northern China, 2008–2011

Xiaobo Wang 1,2,3, Hao Li 1,2,3, Guanglu Jiang 1,2,3, Liping Zhao 1,2,3, Yifeng Ma 1,2,3, Babak Javid 1,2,3, Hairong Huang 1,2,3,
PMCID: PMC4073877  PMID: 24959839

To the Editor: Nontuberculous mycobacteria (NTM), defined as members of Mycobacterium species other than those in the M. tuberculosis complex or M. leprae, are mostly considered to be opportunistic pathogens (1). However, many NTM can and do cause disease in immune-competent hosts. Pulmonary infection by NTM can be a source of diagnostic uncertainty, especially in locations such as in China, where acid-fast staining of sputum samples is the mainstay of diagnosis for tuberculosis (2). NTM are also relatively resistant to many of the first- and second-line drugs used to treat tuberculosis, thus making accurate diagnosis and drug-susceptibility testing critical to clinical management of NTM infections (3). The medical and public health communities have been concerned about increasing prevalence of NTM infection in China, and 2 recent surveys, 1 from Shanghai and another from a rural population in Shandong Province, gave somewhat conflicting reports of the prevalence of these infections (4,5). We therefore decided to conduct a survey of NTM isolates in Beijing from the National Tuberculosis Clinical Laboratory of the Beijing Chest Hospital. We also tested isolates from specimens collected in this laboratory against an extended drug susceptibility panel to determine which drug regimens would be most useful in therapy for various NTM infections.

During January 2008–December 2011, sputum samples collected from 3,714 patients attending the Beijing Chest Hospital with suspected pulmonary tuberculosis were positive for mycobacterial spp. Among the surveillance population, 92% were from northern China, including 13 provinces and the 2 major urban conurbations of Beijing and Tianjin. From our survey, the Han ethnic group accounted for 82% of patients, and 61% of total patients were from urban, rather than rural, areas. Most (59%) of the patients were male, and 40% were attending the hospital for re-treatment of pulmonary tuberculosis; mean age was 51 ± 20 years. Of these mycobacterial isolates, 95 (2.6%) were positive for NTM; NTM were identified during initial screening for resistance to p-nitrobenzoic acid. We identified the strains to species level by sequencing the internal transcribed spacer region of the 16S-23S rRNA and 16S rRNA genes (6), which is able to discriminate between even closely related species such as M. chelonae and M. abscessus (7).

Of the 95 NTM isolates, 38 (40%) were M. intracellulare and 28 (29%) were M. abscessus (Table). Five additional species were also identified: M. fortuitum (8%), M. gordonae (8%), M. kansasii (7%), M. avium (5%), and M. parascrofulaceum (1%). A survey performed recently in Shandong Province also identified M. intracellulare as the most common isolate (4), but in that study, it represented 52 (81%) of 64 cases. By contrast, 2 previous surveys found M. chelonae to be the most commonly isolated species (20% and 27% of isolates) (5,8). However, none of the isolates from our study were M. chelonae. Differences in isolates may represent the representative patient population from which they were derived; M. chelonae was most commonly isolated from hospitals in southern China (5,8). The most common NTM species found in eastern Asia was M. avium complex, in keeping with findings from our study (9). Documenting another trend, the International Union Against Tuberculosis and Lung Disease reported that M. fortuitum was the most frequently encountered species in Turkey (33.9%), the Czech Republic (17.5%), Portugal (16.5%), and other countries in Europe (10).

Table. Species and drug-resistance profiles of 95 nontuberculous mycobacteria strains, northern China, 2008–2011*.

Drugs No. (%) resistant strains in Mycobacterium spp.
Total
M. intracellulare M.abscessus M.fortuitum M. gordonae M.kansassi M. avium M.parascrofulaceum
INH 37 (97.37) 28 (100) 7 (87.5) 6 (75) 3 (42.86) 5 (100) 1 (100) 87 (91.58)
RIF 34 (89.47) 28 (100) 7 (87.5) 2 (25) 0 5 (100) 1 (100) 77 (81.05)
EMB 4 (10.53) 26 (92.86) 7 (87.5) 1 (12.5) 0 2 (40) 0 40 (42.11)
SM 38 (100) 28 (100) 7 (87.5) 4 (50) 6 (85.71) 5 (100) 1 (100) 89 (93.68)
CPM 31 (81.58) 26 (92.86) 4 (50) 1 (12.5) 2 (28.57) 3 (60) 1 (100) 68 (71.58)
AK 31 (81.58) 25 (89.29) 4 (50) 1 (12.5) 1 (14.29) 4 (80) 0 66 (69.43)
PTO 25 (65.79) 27 (96.43) 6 (75) 4 (50) 0 4 (80) 1 (100) 67 (70.53)
PAS 38 (100) 28 (100) 7 (87.5) 8 (100) 7 (100) 4 (80) 1 (100) 93 (97.89)
OFLX 38 (100) 28 (100) 3 (37.5) 3 (37.5) 1 (14.29) 5 (100) 1 (100) 79 (83.16)
LVFX
36 (94.74)
28 (100)
3 (37.5)
2 (25)
0
5 (100)
1 (100)
75 (78.95)
Total 38 (40) 28 (29.47) 8 (8.42) 8 (8.42) 7 (7.37) 5 (5.26) 1 (1.05) 95 (100)

*INH, isoniazid; RIF, rifampin; EMB, ethambutol; SM, streptomycin; CPM, capreomycin; AK, amikacin; PTO, protionamide; PAS, para-aminosalicylic acid; OFLX, ofloxacin; LVFX, levofloxacin.

Drug susceptibility testing (DST) was performed by the proportion method according to the WHO Guidelines for the Programmatic Management of Drug-resistant Tuberculosis, 2011 Update [cited 2014 May 12] http://whqlibdoc.who.int/publications/2011/9789241501583_eng.pdf. We tested 3 first-line anti-tuberculosis drugs (rifampin, isoniazid, and ethambutol) and 7 second-line agents (streptomycin, capreomycin, amikacin, protionamide, para-amino salicylic acid, ofloxacin, and levofloxacin) (Table). If a patient had multiple positive NTM isolates, DST was performed on the last isolate. In agreement with other studies (4,5), ethambutol remained the most useful agent against NTM; its overall resistance rate among isolates tested was 42%. Ranking of second or third agents, however, should be guided by species identification and DST. For example, levofloxacin appears to be a good choice for M. kansasii, M. gordonae, or M. fortiutum infections (overall resistance rate 22%), but a poor choice against M. avium complex infections (overall resistance rate 95%). The second most prevalent species in our study (28% of isolates), M. abscessus, was resistant to the test drugs in >90% of cases, highlighting the difficulties associated with treatment for some NTM infections.

Our study suggests that there has been no substantial increase in the prevalence of NTM in respiratory isolates from persons in northern China. Most of the isolates show substantial and extensive drug resistance, providing major therapeutic challenges for clinicians, especially if patients are treated as they would be for drug susceptible tuberculosis. To guide therapy, both species-level identification and DST of NTM isolates should be performed. Our data suggest that testing the efficacy of some second-line agents, in particular, fluoroquinolones, may be beneficial in identifying further options for therapy.

Acknowledgments

We thank all participants in this study.

This work was supported by the research funding from Infectious Diseases Special Project, Minister of Health of China (2012ZX10003002).

The NTM isolates used in this project were originated from the Beijing Bio-Bank of clinical resources on Tuberculosis (D09050704640000), Beijing Chest Hospital.

Suggested citation for this article: Wang X, Hao Li, Jiang G, Zhao L, Ma Y, Javid B, Hairong Huang H. Prevalence and drug resistance of nontuberculous mycobacteria, Northern China, 2008-2011 [letter]. Emerg Infect Dis. 2014 Jul [date cited]. http://dx.doi.org/10.3201/eid2007.131801

1

These authors contributed equally to this article.

References

  • 1.Thomson RM, Yew WW. When and how to treat pulmonary non-tuberculous mycobacterial diseases. Respirology. 2009;14:12–26. 10.1111/j.1440-1843.2008.01408.x [DOI] [PubMed] [Google Scholar]
  • 2.Cassidy PM, Hedberg K, Saulson A, McNelly E, Winthrop KL. Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology. Clin Infect Dis. 2009;49:e124–9 . 10.1086/648443 [DOI] [PubMed] [Google Scholar]
  • 3.Johnson MM, Odell JA. Nontuberculous mycobacterial pulmonary infections. J Thorac Dis. 2014;6:210–20 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Jing H, Wang H, Wang Y, Deng Y, Li X, Liu Z, et al. Prevalence of nontuberculous mycobacteria infection.China, 2004–2009. Emerg Infect Dis. 2012;18:527–8. 10.3201/eid1803.110175 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Wang HX, Yue J, Han M, Yang JH, Gao RL, Jing LJ, et al. Nontuberculous mycobacteria: susceptibility pattern and prevalence rate in Shanghai from 2005 to 2008. Chin Med J (Engl). 2010;123:184–7 . [PubMed] [Google Scholar]
  • 6.Xiong L, Kong F, Yang Y, Cheng J, Gilbert GL. Use of PCR and reverse line blot hybridization macroarray based on 16S–23S rRNA gene internal transcribed spacer sequences for rapid identification of 34 Mycobacterium species. J Clin Microbiol. 2006;44:3544–50. 10.1128/JCM.00633-06 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Mohamed AM, Kuyper DJ, Iwen PC, Ali HH, Bastola DR, Hinrichs SH. Computational approach involving use of the internal transcribed spacer 1 region for identification of Mycobacterium species. J Clin Microbiol. 2005;43:3811–7. 10.1128/JCM.43.8.3811-3817.2005 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Weimin L, Jiang GJ, Liu Z, Hao H, Cai L, Tian M, et al. Non-tuberculous mycobacteria in China. Scand J Infect Dis. 2007;39:138–41. 10.1080/00365540600951234 [DOI] [PubMed] [Google Scholar]
  • 9.Simons S, van Ingen J, Hsueh PR, Van Hung N, Dekhuijzen PN, Boeree MJ, et al. Nontuberculous mycobacteria in respiratory tract infections, eastern Asia. Emerg Infect Dis. 2011;17:343–9. 10.3201/eid170310060 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Gopinath K, Singh S. Non-tuberculous mycobacteria in TB-endemic countries: are we neglecting the danger? PLoS Negl Trop Dis. 2010;4:e615. 10.1371/journal.pntd.0000615 [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Emerging Infectious Diseases are provided here courtesy of Centers for Disease Control and Prevention

RESOURCES