Chapter

49

Non-tubercular Mycobacteria

INTRODUCTION
Mycobacterium other than human/bovine tubercle bacilli, occasionally
causing human disease resembling tuberculosis, have been called
atypical, anonymous, unknown, tuberculoid unclassified, non-tuberculous
mycobacteria but best designated as mycobacteria other than tubercle bacilli
(MOTT). They are also named environmental or opportunistic mycobacteria
because their natural habitat appears to be soil and water. There is no definite
evidence of their transmission directly from human being to human being
and therefore they have been broadly grouped as “other mycobacteriosis”.
They are distinct from saprophytic mycobacteria e.g. M. smegmatis, M. phlei.
Opportunistic mycobacteria are gaining more importance in developed
countries where tuberculosis has been brought under control, some of
them causing pulmonary disease but their morphology is different from
M. tuberculosis. More increase in HIV infections led to marked increase in
disease caused by atypical mycobacteria, mainly in Western country, but
in developing countries like India where M. tuberculosis is more prevalent,
opportunistic mycobacteria are gaining less importance. This current chapter
deals with epidemiology, clinical features, diagnosis and management of
non-tubercular mycobacteria.

EPIDIMIOLOGY
Most of the non-tubercular mycobacteria (NTM) are ubiquitous in
environment, so that the true incidence is difficult to determine.
574 Clinical Tuberculosis: Diagnosis and Treatment

Notification system varies from country to country and none of them are
accurate.1 Two national surveys in last decades have helped to define the
extent of non-tubercular mycobacteria in United States. The initial study
based on states laboratory reports from 1979–1980 indicated that non-
tubercular mycobacteria comprises one-third of the 32,000 mycobacteria
isolates.2 The most commonly recognized species were Mycobacterium
avium-complex (61%), Mycobacterium fortuitum-complex (19%), and
Mycobacterium kansasii (10%). Most of the reported isolates were from
respiratory specimens. The second surveillance study between 1981–1983
revealed a similar distribution and showed higher rate of NTM among
non-white, women and patients residing in urban areas. The prevalence
of NTM disease in North America is 1.8/100, 000. In 1981, Communicable
Disease Surveillance Center (CDSC) in England and Wales reported that
5% of all mycobacterial pulmonary disease is caused by NTM. In England
and Wales, patients who do not have AIDS, M. kansasii and M. malmoense
were producing pulmonary disease more commonly.3
In India, Mycobacterium tuberculosis is most common and proportion
of NTM has varied from less than 1–28%,4-11 and M. avium complex
and M. fortuitum were isolated in different studies. M. chelonae and
M. fortuitum were among the frequently isolated from clinical specimens
in various hospitals from India. Author in one study reported atypical
mycobacteria in 9.2% of 236 patients of active pulmonary tuberculosis
in Lucknow, most common organism were M. malmoense, M. gordonae,
M. avium intracelluare, M. xenopi, M. fortuitum, M. gastri, M. terrae and
M. flavescense.12 NTM needs culture with strict criteria and in developing
country like India, it is not routinely performed, so there is usual tendency
to ignore such isolates and in the absence of clear-cut guidelines, it is
difficult to find out exact magnitude of atypical mycobacteria.

MODE OF INFECTIONS
Non-tubercular mycobacteria infections can be acquired by variety of
mechanism including inhalation route, ingestion, direct inoculation
after trauma and iatrogenically via syringe, needles, medical instrument
such as bronchoscope, intravenous catheter and surgical skin lesions.
Although animal to human transmission may occurs in some species,
e.g. M. simiae. An increased risk of NTM infections seen in chronic
obstructive pulmonary disese, healed tuberculosis, bronchiectasis, fungal
disease, alveolar proteinosis, pneumoconiosis, rheumatoid disease,
diabetes mellitus, heart disease, alcoholism, achalasia cardia and patients
with partial gastrectomy, AIDS, malignancy and patients receiving
corticosteroids and immunosuppresive drugs.13,14
 Non-tubercular Mycobacteria 575

CLASSIFICATIONS OF NTM
Based on Pigment Production and Rate of Growth
Environmental Mycobacterium have been classified into 4 groups by Runyon
(1959)15 based on pigment production and rate of growth.

Group-1: Photochromogen
These organisms produces a colony that produces no pigment in dark but
when exposed to light for 1 hour in presence of air and reincubated for 24–48
hours, a yellow orange pigment appears. They are slow growing but growth
is faster than M. tuberculosis for examination, M. kansasii, M. marinum,
M. simiae and M. asiaticum.

Group-2: Scotochromogen
These organisms produce colonies and yellow-orange-red pigment in dark,
e.g., M. scrofulaceum, M. gordonae and M. szulgai.

Group-3: Non-photochromogen
These organism produces colonies that produces no pigment in exposure to
light colonies may resemble those of tubercle bacilli. For exmple, M. avium,
M. intracellulare (Battey bacillus), M. xenopi, M. ulcerans, M. malmoense,
M. terrae, M. haemophilum, M. genavense.

Group-4: Rapid grower

These organisms are capable of producing rapid growth, colonies appearing
with in 7 days of incubation at 37 or 25°C. Some rapidly growing mycobacteria
are considered “late pigmenter”. For example, M. chelonae, M. fortuitum,
M. abscessus, M. smegmatis and M. flavescens and M. peregrium.

Based on Location of Disease Production (Table 49.1)

•• Pulmonary disease: M. kansasii, M. avium complex, M. chelonae, M.
fortuitum, M. xenopi, M. malmoense, M. szulgai, M. simiae
•• Lymph node: Lymph node involvement seen in infections in M. avium-
complex, M. scrofulaceum, M. malmoense
•• Skin and soft tissue disease: By most commonly seen in infections with
M. fortuitum, M. chelonae, M. marinum, M. ulcerans, M. abscessus. All
species of NTM can present as skin and soft tissue lesions
•• Bone and joints disease: By most commonly seen in infections with M.
marinum
•• Crohn’s disease: Mycobacterium paratuberculosis
•• Disseminated in non HIV: M. kansasii, M. avium-complex, M. chelonae,
M. scrofulaceum, M. fortuitum, M. haemophilus
•• Disseminated in HIV: By most commonly M. avium complex
576 Clinical Tuberculosis: Diagnosis and Treatment

Table 49.1: Classification of non-tuberculosis mycobacteria according to disease in human

Sl. Clinical Common Growth Morphology Rare Species

No. Disease Species Rate
1. Pulmonary M. avium complex Slow Usually not M. malmoense
M. kansasii (> 7 days) pigmented M. szulgai
M. chelonae Slow Large and M. simae
complex beaded AFB
M. xenopi Rapid smear
(< 7 days) Not pigmented
Slow Pigmented
2. Lymph M. avium complex Slow Not pigmented M. fortuitum
adenitis M. scrofulacum Slow Scotochromogen M. chelonae
3. Skin lesions M. marinum Rapid Photochromogen M. avium
requires low complex
temperature for M. kansasii
isolation
M. fortuitum Rapid Not pigmented
M. chelonae Rapid Not pigmented
M. ulceranse Slow Scotochromogen
requires low
temperature for
isolation
4. Disseminated M. avium complex Slow Isolates from
AIDS patients,
usually pig-
mented
M. kansasii Slow Photochromogen
M. chelonae Rapid Not pigmented
M. haemophilus Slow Not pigmented,
requires hemin
and low
temperature

DISTRIBUTION
Most NTM distributed freely in water and soil but some of them also isolated
from house dust. M. avium16,17 grows well in natural water while M. kansasii18,19
has been found in tap water. Rapid grower species have been isolated from
soil, natural water as well as tap water and water used for dialysis and surgical
solution.

CLINICAL PRESENTATIONS
The most common clinical manifestation is chronic lung disease. Cough,
expectoration, fever, weight loss, hemoptysis, malaise and breathlessness
are most common complaints but 10–40% patients may be asymptomatic.
Evaluation is often complicated by symptoms due to other pre-existing lung
disease. However, lymphatic, skin/soft tissue, bone/joint involvement as well
as disseminated disease are also important manifestations of infection. The
propensity of a specific manifestation varies with the specific species and
certain host factors. The most common form of NTM disease in children is
 Non-tubercular Mycobacteria 577

cervical lymphadenitis. Involvement of lymph nodes is unilateral and non-

tender with minimal systemic symptoms and can lead to sinus formation.
Rapid growers can produce skin and soft tissue infection apart from lung
involvement. Disseminated infections are most commonly associated with
HIV infection and other forms of severe immunosuppression.

DIAGNOSIS
American Thoracic Society modifies laboratory functions that contribute to
the diagnosis and treatment of disease caused by Mycobacterium tuberculosis
and NTM divided into three major category of service offered. These are:
Level I: Collection and transport of specimen, prepration and examination of
smears for acid-fast bacilli (AFB).
Level II: Procedure of level I plus, isolation and identification of
Mycobacterium tuberculosis.
Level III: Procedure of level II, plus identification of NTM. Drug susceptibility
should performed at level II, level III.

Culture Methods for NTM

The isolation of NTM presents the same problems as the isolation of
Mycobacterium tuberculosis. As mycobacteria grows slowly, other bacteria
have to be eliminated from the specimen by prior treatment with acid or
alkali. Two common solid media are available: egg-potato-base (Lowenstein-
Jensen medium) and agar based (Middle Brook 7H10 or 7H11). Specimen
should be inoculated to both type of medium with additional use of broth
medium being useful. This can be standard Middle Brook 7H9 or radio
labeled 7H12 used for rapid isolation in BACTEC system. In slow growing
NTM growth detectable in 2–4 weeks on solid media and 1 week in BACTEC
system with the exception of M. haemophilum for that paper strip containing
hemin (X-factor) used for identification.20

Table 49.2: Cultural characteristics of clinically important non-tubercular mycobacteria

Sl. Species Temperature Pigment Oxygen Tween

No. Range Production Preference Hydrolysis
25 37 45 Light Dark
1. M. kansasii + + – + – A P
2. M. avium complex + + V – – M N
3. M. intracellulare + + V – – M N
4. M. scrofulaceum + + V + + M N
5. M. malmoense + + – – – M V
6. M. xenopi – + + + + M N
A, Aerobic; M, Microaerophilic; P, Positive; N, Negative; V, Variable
578 Clinical Tuberculosis: Diagnosis and Treatment

Identification on Nontubercular Mycobacteria

Several biochemical tests performed to identify species of NTM but principle
test is niacin test that differentiate it from Mycobacterium tuberculosis as
former is negative and latter is highly positive. Other biochemical tests such as
Tween 80 degradation, arylsulphatase test, catalase test are positive for NTM
(Table 49.2). These organisms display P-nitrobenzoate resistance and positive
iron uptake in contrast to M. tuberculosis. Because of sluggish biochemical
reaction several other tests have been reported that yields rapid identification
of Atypical Mycobacteruim are—Thin layer chromatography, gas liquid
chromatography and high pressure liquid chromatography (HPLC).21 HPLC
can also be used in the direct analysis of primary cultures of mycobacteria
grown in BACTEC 7H12B medium (Becton Dickinson), MGIT as well as MB/
BACT and the identification of MAC directly from samples with AFB smear–
positive results. They can be classified at group, species and subspecies
levels by analysis of lipids with such type of investigations. Strains can be
identified with the help of serotyping and simple electrophoretic mobilities
of proteins and isoenzymes. Two recent investigations that are currently in
use to identify atypical Mycobacterium, more rapidly are specific DNA probe
test and BACTEC Nap test (the average time for Nap test is 5 days). Former
method can identify growth from solid and liquid media both. Acridium
ester–labeled DNA probes specific for MAC, M. kansasii, and M. gordonae
have been approved for the rapid identification of NTM. This technique is
based on the release of target 16S rRNA from the organism. Testing can be
performed using isolates from solid or liquid culture media and identification
of these species can be achieved within 2 hours. Studies have shown 100%
specificity with sensitivity between 85–100%. It has been suggested that there
is no use of testing of sensitivity for rifampicin and isoniazid for rapid growers
as they are usually resistant and other drugs must be taken into account.
The current PCR-RFLP method widely adopted for the identification of
NTM is based on the coupling of the PCR of a 441-bp sequence of the gene
encoding the 65-kD heat shock protein (HSP65) followed by restriction
enzyme digestion. The size of the restriction fragments is generally species
specific. DNA sequence analysis with16S rRNA can be of great help in
recognition of various species.

Chest Radiography
There are some difference in the radiological feature of atypical
Mycobacteruim and M. tuberculosis. These producing thin walled cavity
with less surrounding parenchymal infiltrate, less bronchogenic and more
contigous spread of disease and involving apical and anterior segment of upper
lobes and involving pleura overlying the involved areas. Occasionally, they
produce dense pneumonia or solitary pulmonary nodule without cavitations,
basal pleural disease less common and pleural effusion are rarely observed.
 Non-tubercular Mycobacteria 579

Approximately 90% patients of M. kansasii disease and 75% patients of

M. avium complex disease have cavitary infiltrates.22

High-Resolution Computed Tomographic (HRCT) Scan

HRCT scan is indicated if radiological findings are inconsistent with that
of NTM infection such as no evidence of cavitation in radiograph. NTM
pulmonary infections should be suspected when a patient presents with a
compatible clinical picture and has multiple nodular or cavitary opacities
with multifocal bronchiectasis.

Fine-needle Aspiration Cytology

Diagnosis is usually made by FNAC or excision biopsy of the involved lymph
nodes. Only 50–80% of excised nodes will be culture positive.

Tissue Biopsies
Tissue biopsies that are cultured and examined histopathologically are
the most sensitive way to diagnose infections due to rapid growers and
M. marinum. It has been reported that visualization of organisms in the
specimen from the involved site is seen in about 10% of cases and the yield of
culture is not easy to be determined. Polymerase chain reaction can be useful
in identification of NTM such as M. ulcerans apart from smear and culture
of specimens as well as bronchial wash or bronchioalveolar lavage through
bronchoscopy.

Diagnostic Criteria
Many atypical mycobacteria are colonizing the bronchial tree without causing
any disease, so that their culture from sputum is having no pathological
significance. Conventional criterion for diagnosis of disease depends of
infiltrative lesions in radiology including chest radiograph as well as HRCT
scan, isolation of Mycobacterium from sputum smear and culture and
exclusion of other disorders, such as tuberculosis. As these organisms are
commonly found in nature, contamination of culture or transient infection
does occur. Thus, a single positive sputum culture is not sufficient to diagnose
the disease. Culture of the organism from lung biopsy, bronchoalveolar
lavage or pleural fluid or blood culture is of greater significance than an
isolated sputum culture. The American Thoracic Society has recommended
following criteria for diagnosing atypical Mycobacterium which fit best with
Mycobacterium avium complex, M. kansasii and M. abscessus.22
1. Patients having cavitary infiltrate on the chest X-ray, NTM disease is
considered to be present when:
I. Two or more sputums (or sputum and bronchial washing) are AFB
smear positive and/or result in moderate to heavy growth of NTM
on culture.
580 Clinical Tuberculosis: Diagnosis and Treatment

II.Other reasonable causes for disease, e.g. fungal disease, malignancy,

tuberculosis have been excluded.
Approximately 90% patients of M. kansasii disease and 75% patients of
M. avium complex disease have cavitary infiltrates will be diagnosed by
these criteria.22
2. In the presence of non-cavitary infiltrate not known to be due to another
disease, NTM lung disease is considered to be present when:
I. Two or more sputums (or sputum and bronchial washing) are AFB
smear positive and/or result in moderate to heavy growth on culture.
II. Failure of sputum cultures to convert negative with either bronchial
hygiene or 2 weeks of specific mycobacterial drug therapy.
III. Other reasonable causes for disease have been excluded.
The second criterion is presumed to be to exclude colonization rather the
disease state. M. chelonae lung disease is usually non-cavitary and would
be diagnosed by these criteria.
3. In patients with low numbers of organism on sputum culture and/or
concern about the presence of another disease to explain the radiographic
abnormality, a lung biopsy is often required for diagnosis.
I. If the TBLB, percutaneous or open lung biopsy is performed and
biopsy tissue sample yields the organism and shows mycobacterial
histopathology changes (i.e. granulomatous inflammation with or
without AFB), this is sufficient to confirm diagnosis of NTM.
II. If lung biopsy showing negative culture but demonstrates
mycobacterial histopathology changes (in absence of a prior history
of other granulomatous or mycobacterial disease), NTM lung
disease is considered to be present when:
— Two or more sputum (or sputum and bronchial washing) are
culture positive for NTM, even if they are negative for AFB on
smear and result in light growth on culture and other reasonable
causes for granulomatous disease have been excluded.

FEATURES OF NTM
Mycobacterium avium Complex (MAC)
Overall MAC is most common NTM to cause human disease in
immunocompetant patients and 50% of AIDS patients. MAC Includes
commonly 2 organism first M. avium and M. intracellure. These are widely
distributed in water (natural ponds, lakes, swamp, and bogs: public baths,
and public drinking water system), soil and occasionally found in dust,
plants, raw milk, and in cigarette also. Respiratory disease occurs primarily
by aerosol inhalation. This organism also causes cervical lymphadenopathy.
These organisms produce disease in animal also. Radiographic features are
 Non-tubercular Mycobacteria 581

typically divided into primarily fibrocavitary and nodular bronchiectatic

disease, former being more common in older men with overlying lung
disease.

M. kansasii
It is most common organism after MAC in different parts of world and found
uncommonly in Australia. This is widely distributed in water mainly tap water,
in which able to survive for longer periods.23-25 Respiratory disease occurs
primarily by aerosol inhalation and occasionally causes lymphadenopathy.
The disease is very similar to that caused by M. tuberculosis. Disease pattern
in immunocompromized patients is disseminated. Radiographic appearance
include upper lobe and thin walled cavitary opacities.

M. marinum
M. marinum is exclusively skin pathogens, occasionally there is extension
into adjacent soft tissue or regional lymph nodes and causing chronic ulcers
and granulomatous lesions in the skin. It has been regarded as a causative
organism for swimming pool granuloma. Transmission of infections occurs
by producing infection with contaminated fresh or salt water.26 Most of
reported cases are seen in the fishing industry.

M. xenopi
M. xenopi has been found in tap water27,28 and shower heads and responsible
to produce nosocomial infections due to contaminated water system. These
organisms can grow at 45°C and isolated from hot and cold water. They are
producing pulmonary disease frequently. Typically, patients present with
underlying chronic obstructive pulmonary disease (COPD) and radiographic
features similar to that of MAC infection.

M. chelonae
The M. chelonae complex which includes M. chelonae, M. fortuitum and M.
abscessus and widely distributed in natural rivers, lakes, seas, human drinking
and waste water and frequently responsible for nosocomial infections from
several sources.29 These organisms are producing commonly lung and skin
manifestations.

M. scrofulaceum
M. scrofulaceum found in natural lakes and rivers also in raw milk or other
dairy products and very rarely in drinking water.25 This commonly causes
cervical lymphadenitis in children’s next to M. avium complex. Pulmonary
infections seen less commonly and usually associated with underlying lung
disease mainly COPD, pneumoconiosis and previous tuberculosis.
582 Clinical Tuberculosis: Diagnosis and Treatment

TREATMENT
The principles of treating NTM infections are different from that of
Mycobacterium tuberculosis. The decision to treat is based on the potential
risks and benefits for the individual patient. The clinician should know the
limitation that in vitro susceptibility results for many NTM do not correlate
with clinical response. There are various species of NTM for which different
drugs and regimens are indicated. Duration of treatment is much longer than
that of tuberculosis due to low bactericidal activity and high in vitro resistance.
Surgical resection is more frequently indicated than medical management.
Most of the first line antituberculosis drugs with good in vitro activity
against MTB has 10 to 100 times less activity against Mycobacterium avium
complex, the diminished activity believed to result from the presence of
lipophilic cell wall, which prevents drug penetration. The cornerstones
of MAC therapy are primarily the macrolides such as clarithromycin and
azithromycin, and ethambutol in combination with companion drugs,
usually a rifamycin and injectable aminoglycoside possibly streptomycin or
amikacin. Asymptomatic patients with stable radiological picture should be
managed by observation only, if their sputum remains clear. However, the
recommended initial regimen for patients with nodular/bronchiectatic lung
disease is a three times weekly regimen including clarithromycin (1000 mg)
or azithromycin (500 mg), ethambutol (25 mg/kg) and rifampin (600 mg).
In cases having severe nodular/bronchiectatic lung disease or presence of
fibrocavitation on radiography, daily regimen being prescribed. Injectable
aminoglycosides can be used optionally depending on disease severity
and treatment response. A more aggressive and less well-tolerated regimen
including clarithromycin (1000 mg/day) or azithromycin (250–300 mg/day),
ethambutol (15 mg/kg/day), a rifampin (450–600 mg/day) or rifabutin (150–
300 mg/day) and injectable aminoglycoside for first 2 or 3 months of therapy
is recommended for patients with severe and extensive disease or having
previous treatment history. Surgery can be considered in such cases.
Macrolides should not be used as a single drug therapy in order to
prevent emergence of drug resistant strains. In case of development of
macrolide resistance, patient should be started on recommended therapy that
comprises of four drug regimen of isoniazid (300 mg), rifampicin (600 mg)
or rifabutin (300 mg), and ethambutol (25 mg/kg for first 2 months then 15
mg/kg) with streptomycin or amikacin preferably for initial 3–6 months and
surgical resection (debulking) of disease.47 The optimal regimen still requires
further modification. The usual recommendation is that patients will be
treated for 18–24 months and for atleast 12 months after sputum conversion.
This four drug regimen has not been proved by comparative trials but shown
sputum conversion up to 80%.30,31 AFB smears and cultures of sputum should
be done monthly during early part of therapy to assess response but these are
not specific indicator of response. Occasionally, positive sputum culture after
 Non-tubercular Mycobacteria 583

sputum conversion does not mean treatment failure or relapse as definite

relapses while still receiving therapy or after discontinuation of therapy
is common about 20% or higher with recommended four drug therapy.30
Patients who fail to convert their sputum culture after 12 months of therapy
should be reassessed. In these patients, drug therapy is more complex and
higher incidence of toxicity. The alternative drugs are, cycloserine (250 mg
twice a day), ethionamide (250 mg twice a day), rifabutin (600 mg daily),
clofazimine (100–200 mg daily), ciprofloxacin (1000–1500 mg daily) or
moxifloxicin (400 mg/day) but all of them are limited by little or no evidence of
clinical efficacy and toxicity. Monitoring of the patients receiving above drugs
is very essential. Patients whose disease is localized to one lobe of lung and
who can tolerate resection surgery should be considered especially if there is
poor response to drug therapy. Resected pulmonary nodules that prove to be
due to MAC requires no further treatment in the absence of evidence of other
MAC disease or immunosuppression.32,33
Disseminated MAC is a late opportunistic infection in immu­
nosuppressed patients with AIDS. All patients should be treated with
clarithromycin, 1000 mg/d or 500 mg twice daily or azithromycin as an
alternative drug at a dose of 500 mg/day, ethambutol (15 mg/kg/day) and
rifabutin (300 mg/day). Daily regimen is being preferred over intermittent
therapy in such cases. Clarithromycin is more potent against M. avium
and reducing bacillary count up to 99%34. Efficacy of drugs are limited for
patients having macrolide resistant strains. Drugs that should be considered
for inclusion are injectable aminoglycosides and a quinolone such as
moxifloxicin. Clofazimine should not be used as it has been associated with
excess mortality in patients having disseminated MAC.48 Monitoring of
treatment is highly recommended in patients with AIDS in order to prevent
various complications related to adverse drug effects and pharmacokinetic
interactions with antiretroviral therapy.
The recommended therapy for M. kansasii disease is the regimen
of isoniazid 5 mg/kg/day (300 mg), rifampicin 10 mg/kg/day (600 mg),
ethambutol (15 mg/kg) and pyridoxine (50 mg/day) given daily for 18
months. Intermittent therapy can be successful.49 The regimen should
be maintained for a further period of one year after achieving culture
negative status. Pyrazinamide is not useful for M. kansasii as all isolates
are resistant. Patients whose organism resistant to rifampicin as a results of
previous therapy have shown response with high dose of isoniazid (900 mg),
pyridoxine (50 mg), ethambutol (25 mg/kg) and sulfamethoxazole (3 g) for
18–24 months. The oral therapy has been combined with daily or five times
per week streptomycin or amikacin for 2–3 months followed by intermittent
streptomycin or amikacin for atleast 6 months. Results with this regimen
showed 88% sputum conversion after 10 weeks. M. kansasii is second most
common cause of disseminated lung disease.35 The treatment regimen for
disseminated disease should be the same as for pulmonary disease.
584 Clinical Tuberculosis: Diagnosis and Treatment

M. marinum causing skin diseases commonly. Treatment includes

simple observation of minor lesions, surgical excision, antibiotics
(clarithromycin, azithromycin as an alternative, doxycyclin or trimethoprim-
sulfamethoxazole combinations) and antituberculosis drugs (rifampicin
600 mg and ethambutol 15 mg/kg daily), given for minimum 3 months
durations.38-41 Susceptibility testing is not routinely recommended and
should be reserved for cases of treatment failure. Disease caused by M.
malmoense is being treated by regimen containing isoniazid, rifampicin
and ethambutol, with and without quinolones and macrolides for 18–24
months.42,43 However, infection caused by this organism is difficult to treat
and optimal chemotherapy needs to be considered. M. xenopi shows variable
pattern of drug sensitivity in vitro often resistant to rifampicin, isoniazid, and
ethambutol. Combination of clarithromycin, rifampicin and ethambutol is
recommended and surgical resection is indicated in case of patients with
sufficient lung function and who fails to respond to chemotherapy.44-46
Efficacy can be improved by addition of quinolones particularly moxifloxicin
and initial course of streptomycin. Therapy should be continued until the
patient has maintained negative sputum cultures while on therapy for
12 months. M. fortuitum, M. chelonae and M. abscessus cause cutaneous
diseases more commonly and are resistant to first line antituberculosis
drugs (Table 49.3). All these organisms are susceptible to amikacin (100%),
ciprofloxacin (100%), sulfonamides (100%), cefoxitin (90%), imipenem
(100%), and doxycyclin (40%), erthromycin (30 to 80%), tobramycin (100%).37
The only curative therapy is surgical resection of involved lung combined with
multidrug chemotherapy. The optimal therapy seems to be questionable but
a regimen can be prescribed including clarithromycin with a second agent
being selected on the basis of in vitro susceptibilities. Success depends on the
existence of negative sputum cultures throughout 12 months of treatment.
For lymphadenitis in children recommended treatment is excisional surgery
without chemotherapy.36 The success rate with this procedure is about 95%.
For children with recurrent disease, a second surgical procedure is usually
performed. A multidrug therapy is recommended in patients with recurrence
of disease two or more after surgical excisions.

Table 49.3: Sensitivity of NTM to individual antituberculosis drug in vitro

Sl. Species Strept- INH Rifam- Etham- Ethion- Capre- Cyclo- Clarith- Cipro
No. omy- picin butol amide omycin serine romy- floxa-
cin cin cin
1. M. kansasii B R S S S B S S V
2. MAC R R R R S R S S R
3. M. malmoense R R V V S R S S S
4. M. xenopi S R V R S S S S S
B, Borderline; R, Resistant; S, Sensitive; V, Variable
 Non-tubercular Mycobacteria 585

REFERENCES
1. Messiner G, Anz W. Sources of MAC infection resulting in human disease. Am rev respire
dis. 1977;116:1057.
2. Good RC, Snider DE. Isolation of nontuberculous Mycobacterium in the United States, 1980.
J infects Dis. 1982;146:829-33.
3. Woods GL, Washington JA II. Mycobacterium other than Mycobacterium: review of
microbiologic and clinical aspects. Rev infect dis. 1987;9:275.
4. Thomas KL, Joseph S, Subbaih TV, Selkin JB. Identification of tubercle bacilli from Indian
patients with pulmonary tuberculosis. Bull world Health organ. 1961;25:747-52.
5. Patel IU, D’Souza TJ, Sayed BA. A bacteriological study of Mycobacterum tuberculosis in
Baroda. Indian J Med Sci. 1966;20;924-9.
6. Kulkarni KG, Frimodt-Moller J. Bacteriological study of mycobacteria isolated from cases of
cervical lymphadenitis. Proceedings of the 24th TB and chest conference. Trivandrum, India, p391.
7. Parmasivan CN, Govindan D, Prabhkar R. Somasundaran R, Subbamal S, Tripathy SP.
Species level identification of nontuberculous mycobacteria from south India BCG trial area
during 1981. Tubercle. 1985;66:9-15.
8. Kaur H, Chitkara NL. A study of atypical acid fast bacilli (culture and biochemical
characateristics). Indian J Tuberc. 1964;12:16-8.
9. Katoch K, Katoch VM, Dutta AK, Sharma VD, Ramu G. Chest infection due to M. Fortuitum in
a case of lepromatous leprosy- a case report. Indian J Lepr. 1985;57:399-403.
10. Chakrabarti A, Sharma M, Dubey ML. Isolation rates of different mycobacterial species from
chandigarh (north India.) Indian J Med Res. 1990;A91:111-4.
11. Singh S, Rattan A, Kumar S. Severe cutaneous Mycobacterium chelonei infection following
a yellow jacket sting (letter). Tuber lung dis. 1992;73:305-6.
12. Babu KS, Mukerji PK, Prasad R, Aggarwal SK. Atypical mycobacteria in patients of pulmonary
tuberculosis in Lucknow. Ind J Tub. 1997;44:56(Abstract).
13. Jonhson WG Jr, Nicholson DP. Pulmonary disease due to M. k.: an analysis of some factors
affecting prognosis. Am rev respire dis. 1969;99:73.
14. Karsell PR. Achlasia, aspiration and atypical mycobacteria. Mayo clin proc. 1993;68:1025.
15. Runyan EH. Anonymous mycobacteria in pulmonary disease. Med Clin North Am. 1959;
43:273.
16. Paull A. An enviormental study of opportunistic mycobacteria. med lab technol. 1973;30:11.
17. Brooks RW, Parker BC, et al. Epidemiology of infection by NTM. V.Numbers in eastern united
states soil and correlation with soil characteristics. Am rev respire dis. 1984;130:630.
18. Joyson DM.WATER: the natural habitat of M. kansasii. Tubercle. 1979;60:77.
19. Mc Swiggan DA, Collins CH, et al. The isolation of M. kansasii and M. xenopi from water
system. Tubercle. 1974;55:291.
20. Vadney FS, Hawkins JE. Evaluation of a simple method for growing Mycobacterum
haemophilum. J Clin Microbiol. 1985;22:884-5.
21. Butler WR, Ahearn DG, Kilburn JO. High performance liquid chromatography of myolic
acids as a tool in the identification of corynebacterium, Nocardia, Rhodococcus, and
Mycobacterium species. J clin Microbiol. 1986;23:182-5.
22. Ahn CH, McLarty JW, Ahn SS, Ahn SS, Hurst GA. Diagnostic Criteria for pulmonary disease
caused by Mycobacterium Kansasii and Mycobacterium intracellulare. Am Rev Respir dis.
1982;12:5388-91.
23. Reich JM, Jhonson RE, et al. Mycobacterium avium complex pulmonary disease: incidence,
presentation and response to therapy in a community setting. Am rev respire dis.
1991;143:1381.
24. Falkinham JO. Epidemiology of infection by non-tuberculosis mycobacteria. Clin microbial
rev. 1996;9:177.
586 Clinical Tuberculosis: Diagnosis and Treatment

25. Eaton T, Falkinham JO, et al. Recovery of MAC from ciggarette. J.Clin Microbiol.
1995;33:2757.
26. Zeligman I. Mycobacterium granuloma: a disease acquired in the tributaries of Chesapeake
Bay. Arch Dermatol. 1972;26:106.
27. Collins CH, Yates MD. Infection and colonization by M. kansasii and M. xenopi: aerosols as
a possible source? J Infect. 1984;8:178.
28. Gross WM, Hawkins JE, Murphy DB. Origin and significance of M. xenopi in clinical
specimens: I. Water as a source of contamination. Bull Int Union Tuberc. 1976;51:267.
29. Collins CH, Grange JM, Yates MD. A review Mycobacterium in water. J Appl Bacteriol.
1984;57:193.
30. Ahn CH, Ahn SS, Anderson RA, Murphy DT, Mammo A. A four drug regimen for initial
treatment of cavitary disease caused by Mycobacterium avium-complex. Am Rev Respir Dis.
1984;134:438-41.
31. Seibert AF, Bass JB. Four drug therapy of pulmonary disease due to Mycobacterium-avium
complex (abstract). Am Rev Respir Dis. 1989;139AJ.
32. Corpe RF. Surgical management of pulmonary disease due to Mycobacterium avium
intracellulare. Rev Infect Dis. 1981;3:1064-7.
33. Moran JF, Alexander LG, Staub EW, Young WG, Sealy WC. Long-term results of pulmonary
resection for atypical mycobacterial disease. Ann Thorac Surg. 1983;35:597-604.
34. Barradell LB, Plosker GL, et al. Clarithromycin. A review of its pharmacological properties
and therapeutic use in Mycobacterium avium- intracellulare complex infection in patients
with AIDS. Drugs. 1993;46:289.
35. Ahn CH, Wallace RJ Jr, Steele LC, Murphs DT. Sulfonamide containing regimens for
discussed by rifampin-resistant Mycobacterium sasii. Am Rev Respir Dis. 1987;135:10-6.
36. Crawford JT, Bates JH. Analysis of Plasmids in Mycobacterium avium-intracellulare isolates
from persons with acquired immunodeficiency syndrome. Am Rev Respir dis. 1986;134: 659-61.
37. Swenson JM, Wallace RJ Jr, Silcox VA, Thornsberry C. Antimicrobial susceptibility testing of
5 subgroups of Mycobacterium fortuitum and Mycobacterium chelonae. Antimicrob agent’s
chemo ther. 1985;28:807-11.
38. Kin R. Tetracycline therapy for atypical granuloma. Arch Dermatol. 1974;110:299.
39. Lorial PR. Minocycline hydrochloride treatment for atypical acid-fast infection. Arch
Dermatol. 1976;112:517-9.
40. Black MM, Eykyn, S. The success ful treatment of tropical fish tank granuloma (Mycobacterium
marinum infections). Arch intern Med. 1986;146:902-4.
41. Chow SP, Ip FK, Lau JHK, et al. Mycobacterium marinum infection of the hand and wrist. J
Bone Joint surg (AM). 1987;69-A:1161-8.
42. Bollert FGE, Watt B, et al. Non-tuberculosis pulmonary infections in Scotland: a cluster in
Lothion? Thorax. 1995;50:188.
43. France AJ, McLeod DT, Calder MA, Seaton A. Mycobacterium malmoense infections in
Scotland: an increasing problem. Thorax. 1987:42:593.
44. Banks J, Hunter AM, Campbell IA, et al. Pulmonary infections with M. xenopi: review of
treatment and response. Thorax. 1984;39:376.
45. Smith MJ, Citron KM. Clinical review of disease caused by M. xenopi. Thorax. 1984;39:376.
46. Costrini AM, Mahler DA, Gross WM, et al. Clinical and roentrographic features of nosocomial
disease due to M. xenopi. Am rev respire dis. 1981;123:104.
47. Griffith DE, Brown-Elliott BA, et al. Clarithromycin-resistant Mycobacterium avium complex
lung disease. Am J Respir Crit Care Med. 2006;174:928-34.
48. Chaisson RE, Keiser P, Pierce M, et al. Clarithromycin and ethambutol with or without
clofazimine for the treatment of bacteremic MAC disease in patients with HIV infection. AIDS.
1997;11:311-7.
49. Griffith DE, Brown-Elliott BA, Wallace RJ Jr. Thrice-weekly clarithromycin-containing
regimen for treatment of Mycobacterium kansasii lung disease: results of a preliminary
study. Clin Infect Dis. 2003;37:1178-82.