Table III.

Differences between non-tuberculous mycobacteria (NTM) and Mycobacterium tuberculosis (Mtb)

Characteristics	NTM	Mtb
Nomenclature	NTM have several names: MOTT, atypical mycobacteria, anonymous mycobacteria and environmental mycobacteria. The preferred name is NTM.	Mtb is an important member of MTBC responsible for human TB. Other members include M. africanum, M. bovis, M. canettii, M. caprae and M. pinnipedii.
NTM species distribution	Nearly 200 species are described using DNA sequencing (a new species is defined as >1% difference in nucleotides); NTM species have regional variation due to climatic and geographical factors.	Mtb strains [Beijing (most pathogenic), Cameroon, CAS, EAI, Haarlem, LAM, Manu (Indian), and S] have geographical variation.
Biochemical tests	No single biochemical test is available for the diagnosis of NTM species. Some of the NTM species show positive results with niacin accumulation test (M. simiae, M. chelonae), nitrate reduction test (M. ulcerans, M. szulgai, M. fortuitum, M. smegmatis, M. kansasii), catalase test (M. fortuitum, M. chelonae, M. abscessus, M. ulcerans, M. szulgai, M. kansasii), citrate utilization test (M. chelonae, M. smegmatis), urea hydrolysis test (M. kansasii, M. marinum, M. simiae, M. szulgai, M. scrofulaceum), McConkey agar (without crystal violet) (M. fortuitum, M. abscessus) test and tellurite reduction (M. avium, M. intracellulare, M. simiae, M. fortuitum, M. abscessus).	Mtb is niacin positive, reduces nitrate and is negative for heat-stable catalase test.
Microscopic morphology	Absence of characteristics serpentine cords in acid-fast smears.	Characteristic serpentine cording seen as rope-like aggregates in which long axis of the bacilli is parallel to the long axis of the cord in acid-fast smears.
Growth characteristics in cultures	Rapidly growing (<7 days) and slowly growing (≥7 days) mycobacteria, growth rates are slower than other bacteria (Pseudomonas aeruginosa and Escherichia coli).	Mtb are slowly growing mycobacteria and take ~2 wk to grow. Ordinary bacteria may take ~20 min to 12-24 h in the laboratory. Mtb colonies are rough, cauliflower-like and light buff in colour.
Differential identification	Difficult to differentiate NTM from Mtb only on the basis of positive acid-fast smear. Culture is important in differentiating from P. aeruginosa, Staphylococcus aureus, Nocardia, Aspergillus and Sporothrix, etc.	Both smear and culture should be done.
Transmission	Person-to-person transmission does not occur except for M. abscessus among cystic fibrosis patients.	Mtb is highly transmissible through airborne route especially in PTB with cavitary disease and high bacillary loads.
Route of entry	Infection occurs mainly by inhalation, ingestion or direct inoculation. Airborne NTM are a major source of entry for NTM-PD. In advanced HIV/AIDS, gut colonization with subsequent haematogenous dissemination occurs.	Smaller cough droplet nuclei (<1-10 µM) carrying Mtb reach terminal bronchioles and alveoli and establish infection.
Pathogenicity potential	Opportunistic organisms	Highly pathogenic and obligate parasites
Virulence	Generally, NTM have low virulence.	Highly virulent
	M. kansasii is more virulent among NTM.
Latent infection	No evidence of latent NTM infection	Systematic data are available regarding LTBI especially in low TB-burden countries.
		Efforts should be made to differentiate between LTBI and active disease in high TB burden settings.
Case notification	It is not essential to notify laboratory confirmed, newly diagnosed NTM cases. NTM disease notification is practiced only in a few countries.	Systematic TB notification is encouraged and the global TB report is published annually on a regular basis by the World Health Organization.
Pulmonary: extrapulmonary disease proportions	Pulmonary: Extrapulmonary 80-90%: 10-20% in HIV-negative. Disseminated NTM disease occurs in severely immunocompromised individuals such as advanced HIV/AIDS.	Pulmonary 80-85%: extrapulmonary 15-20% in HIV-negative and pulmonary 40-50%: extrapulmonary 50-60% in HIV/AIDS.
Risk factors	NTM-PD usually occurs in individuals with pre-existing lung disease or in those with quantitatively impaired mucociliary function or in individuals who are heterozygous for CFTR mutations.	TB can involve both healthy and destroyed lungs. Risk factors include: malnutrition, tobacco smoking, chronic alcohol intake, diabetes mellitus, overcrowding, HIV/AIDS, head or neck cancer, leukaemia, or Hodgkin’s disease, drugs including corticosteroids, TNF-α inhibitors or receptor blocker.
	Lady Windermere syndrome occurs in post-menopausal non-smoking females with nodular-bronchiectasis, several skeletal abnormalities, increased adiponectin and decreased leptin and oestrogen levels, abnormalities in fibrillin gene, high prevalence of gastroesophageal reflux disease and increased susceptibility to NTM infections.
NTM species predilection for various organs	Pulmonary: MAC, M. kansasii, M. xenopi, M. malmoense, M. abscessus, M. fortuitum M. simiae	No such predilection for body organs is known in TB.
	Skin: M. ulcerans, M. marinum, M. abscessus, M. chelonae, M. fortuitum
	Soft tissues: M. chelonae and M. fortuitum
	Lymphadenitis: MAC but can occur with other NTM species also.
	Disseminated NTM disease: Most commonly due to MAC but other species can also produce disseminated disease.
Radiographic patterns in MAC-pulmonary disease	Three types of radiographic patterns occur in MAC NTM-PD:	PTB Primary complex (usually in children)
	Cavitary: In elderly smokers with COPD patients.	Progressive pulmonary disease
	NB: Predominantly in post-menopausal non-smoking females; bilateral bronchiectasis, multiple nodules and tree-in-bud appearance on HRCT, some may also have small cavitary lesions.	Post-primary PTB: Cavitary, atelectasis, consolidation Miliary PTB
	Hypersensitivity pneumonitis-like NTM pulmonary disease due to MAC and M. immunogenum.	Sequelae such as fibrotic and calcified lesions
Clinical relevance of NTM isolates in respiratory specimens	Clinical relevance of isolated NTM species versus activity of the underlying pulmonary disease should be assessed. Colonization in the host and contamination in the laboratory must be ruled out. Causality association of the particular isolated NTM species with the pulmonary disease should be carefully established before starting the treatment.	Mtb produces both latent TB infection and active disease. Active TB disease must be ruled out appropriately before starting the treatment.
Drug susceptibility testing (DST)	DST for NTM is controversial because of poor correlation between in vitro DST pattern and in vivo treatment response and outcomes. According to CLSI (2018) guidelines16, initial and recurrent MAC and M. kansasii be tested for DST.	Universal DST should be performed and treatment should be carried out as per sensitivity profile of Mtb. DS-TB, H monoresistance, MDR-TB and XDR-TB should be treated with as per National Guidelines, and tolerance of drugs.
	Both phenotypic and genotypic DST are performed.
	For MAC, perform DST against macrolides (clarithromycin as a class agent) and amikacin; for M. kansasii, against rifampicin and clarithromycin.
	RGM species (and subspecies) show different drug resistance patterns and DST should be selectively tested for various antibiotics (macrolides, amikacin, tobramycin, imipenem, trimethoprim-sulphamethoxazole, doxycycline, minocylcine, tigecyline, cefoxitin linezolid) DST, erm (41) gene status should be done in M. abscessus.
	Information about erm (41) gene and phenotypic DST for clarithromycin should be done on days 3-5 and 14 in case of M. abscessus.
Treatment	ATS (2007)17 and BTS (2017)1 ATS/ERS/ESCMID/IDSA18 guidelines on NTM diseases should be followed.	National guidelines should be followed for treatment of drug sensitive and drug-resistant TB.
Treatment outcomes	Treatment outcomes differ among NTM species and subspecies.	Globally, treatment outcomes in case of drug-sensitive TB are good. Treatment of drug-resistant TB is still a challenge and global rate of successful treatment is 56% only. With newer drug regimen(s), treatment success rates are likely to improve in future.
Prevention	Exposure to NTM from the environmental sources especially household water systems, hospital settings and soil should be avoided. In HIV/AIDS patients (CD4 T-cells counts <50/μl), antimicrobial prophylaxis includes administration of azithromycin (1200 mg/weekly) or clarithromycin (500 mg twice daily) or rifabutin (300 mg/day) along with antiretroviral drugs till CD4 cell count is >100 cells/μl for three months.	Exposure to smear positive PTB should be avoided to halt TB transmission. Chemoprophylaxis for latent TB infection (active TB disease must be ruled out in high TB-burden countries), various treatment options include: isoniazid daily for 6 or 9 months, or combination of rifapentine and isoniazid once weekly for 12 wk or combination of rifampicin and isoniazid daily for 3-4 months or rifampicin alone daily for four months.
Vaccines	No vaccine is available at present	BCG vaccine is recommended in high TB burden countries to prevent severe form of TB (miliary and central nervous system TB); newer TB vaccines such as M72/AS01, M. vaccae, MVA85A etc., are in clinical trials. M72/AS01 was significantly protective against TB disease in a Phase IIb trial in Kenya20.

Disseminated disease: Involvement of two or more non-contiguous body sites through haematogenous route. Note: Underlying oesophageal disease must be ruled out in NTM-PD due to RGM especially M. fortuitum. NTM-PD, NTM-pulmonary disease; MTBC, Mtb complex; CAS, Central Asian strain; EAI, East African Indian strain; LAM, Latin American-Mediterranean strain; COPD, chronic obstructive pulmonary disease; SGM, slowly growing mycobacteria; RGM, rapidly growing mycobacteria; CLSI, Clinical and Laboratory Standards Institute; ATS, American Thoracic Society; BTS, British Thoracic Society; ATS/ERS/ESCMID/IDSA, American Thoracic Sciety European Respiratory Society European Society of Clinical Microbiology and Infectious Diseases Infectious Diseases Society of America; erm, erythromycin ribosome methylation; MOTT, mycobacteria other than TB; LTBI, latent TB infection; CFTR, cystic fibrosis transmembrane conductance regulator; TNF, tumor necrosis factor; MAC, Mycobacterium avium complex; NB, nodular/bronchiectatic; HRCT, high-resolution computed tomography; MDR, multidrug resistant; XDR, extensively drug resistant; PTB, pulmonary TB; BCG, bacille Calmette-Guerin. Source: Refs 1,2,3,4,5,6,9,12,13,14,15,16,17,18,19,20