11/3/2019

Infections due to
Nontuberculous
Mycobacteria

Mycobacteria Classification
• Depends on speed of growth, morphology, pigmentation of
colonies on solid media, and biochemical reactions
• 12 W is often required for identification
• Mycobacterium tuberculosis complex
- M. tuberculosis
- M. bovis
- M. africanum
• M. leprae
• Atypical mycobacteria = mycobacteria other than
tuberculosis (MOTT) = nontuberculous mycobacteria (NTM)

1
 11/3/2019

Isolation of NTM
• Blood cultures requires special medium
• Some do not grow well on solid medium
• Culture in liquid broth / Bactec system, shortens time to
identify positive culture
• Molecular probes used for rapid identification if positive culture

NTM Infections in AIDS and other

Immunodeficiencies - Disseminated Infections
Etiology
• Majority caused by M. avium complex (MAC)
• This group include: M. avium and M. intracellulare (MAI)
• AIDS patients with localized NTM diseases often have
positive blood cultures

Epidemiology and Host Factors

• By ingestion: GI symptoms often predominate
and intestinal submucosa is intensely involved
• Hospital hot-water systems source of isolated clusters cases
• Disseminated infections in severely immunosuppressed
patients, or extensive pulmonary disease
• AIDS, risk NTM correlates with depletion of CD4 < 100

Clinical Manifestations
• Prolonged fever, night sweats, weight loss
• Signs of abdominal involvement on CT or US:
hepatosplenomegaly, swelling of abdominal lymph nodes
→ diarrhea and/or abdominal pain
• Anemia and leukopenia are frequent
• Suspicion of NTM should prompt request for BC

2
 11/3/2019

Diagnosis
• BC on special media are the cornerstone of Dx
• 2 to 3 BC are sufficient
• Liquid cultures become (+) earlier (7-14 D)
• Because liver and BM are often involved in disseminated
NTM, bacteria may be visible in AFB biopsies

Treatment
• Preferred regimen for disseminated NTM is
- rifabutin + clarithromycin + ethambutol
• Many recommend lifelong treatment
• Reasonable to discontinue treatment if
- symptoms have lessened
- BC have become negative
- CD4 have recovered >100/uL with HAART

NTM Infections in AIDS and other

Immunodeficiencies
Localized Infections

Pulmonary Disease
• NTM in sputum / BAL with no evidence of lung damage
require no treatment
• Isolation of M. kansasii is clinically significant:
- often predominant in upper lobes
- fever, cough, infiltrates, and cavities
- BC are often positive
- rifampin (600 mg/d) + isoniazid (300 mg/d)
- treatment for 18-24 M

3
 11/3/2019

Skin Disease
• MAC are rarely associated with skin manifestations as
- nodules
- ulcers
- areas of erythema
- pustules
- abscesses
- panniculitis
• Skin biopsies and BC establish Dx

M. haemophilum
• Involve skin, bones, joints, and lungs
• Most have positive BC
• Skin lesions are nodular, may ulcerate, & are disseminated
• Treatment follow guidelines for MAC

NTM Infections In Immunocompetent

Patients: Pulmonary Disease
Etiology
• Most frequent: M. intracellulare, M. avium, and M. kansasii
• Identification: important in therapeutic choice
Epidemiology and Host Factors
• NTM are ubiquitous in the environment
• Low pathogenicity
• Preexisting lung disease: predisposing factor
Clinical Manifestations
• Chronic cough, low-grade fever, malaise, hemoptysis
• Symptoms may be masked by those of underlying
disease process

4
 11/3/2019

Treatment
• May be managed by follow-up without treatment,
resection or drug therapy
• May present as solitary pulmonary nodule that, once
resected, requires no treatment
• Drugs for M. avium or M. intracellulare
• Indications for surgery
- disappointing response to antibiotics
- presence of localized disease
- absence of contraindications (especially impaired
respiratory functions)
• Duration 18 to 24 M

Lymphadenitis
• Occurs mostly in children between 1 & 5 y
• Painless swelling of one or a group of nodes
• Usually affects the anterior cervical chain
• Nodes may rapidly increase in size, with fistulas to the skin
• M. scrofulaceum or MAC most common cause
• Treatment is excision without chemotherapy

Mycobacterium marinum Swimming-Pool and

infection on the hand Fish-Tank Granuloma

5
 11/3/2019

Swimming-Pool and Fish-Tank Granuloma

• Between 1 W and 2 M (usually 2 to 3 W)
• After contact with contaminated tropical fish tanks, swimming
pools, violet nodule / pustule appears at site of minor trauma
• Form a crusted ulcer or small abscess or may remain warty
• Lesions are multiple and disseminated in immunosuppressed
• Causative organism is M. Marinum
• Dx: history, isolation of M. marinum after biopsy and culture
• Lesions often heal spontaneously
• In cases of persistence or dissemination, at least 3 M
- rifampin with ethambutol
- trimethoprim-sulfamethoxazole
- minocycline

Infections Linked to
Injections and Surgery

• Nodular skin lesions esp immunosuppressed

• In some, associated lymphatic spread
• Many linked to injection; Diabetic are at high risk
• Keratitis & corneal ulceration after surgery or injury
• Epidemics following cardiac surgery linked to contaminated
ice packs and porcine heart valves
• Usually due to M. fortuitum, M. chelonae, or
M. abscessus; Referred to M. fortuitum complex
• Rapidly growing: colonies appear 3 to 7 D after inoculation
• Debridement is best + 2-3 antibiotics

6
 11/3/2019

Leprosy
(Hansen's Disease)

Mycobacterium leprae
• Nonfatal, chronic infectious disease
• Grows best in cooler tissues (skin, peripheral nerves,
anterior chamber of the eye, upper respiratory tract, testes)
sparing warmer areas (axilla, groin, scalp, midline of back)

Etiology
• Obligate intracellular bacillus
(0.3-1 μm wide; 1-8 μm long)
• Is acid-fast, indistinguishable from other mycobacteria
• Produces no known toxins
• Penetrate and reside within macrophages
• May survive outside the body for 7 - 10 D

7
 11/3/2019

Demographics and Transmission

• Associated with poverty and rural residence

• Peak onset: 2nd-3rd decades of life
• Route of transmission remains uncertain
- nasal droplet infection
- contact with infected soil
- insect vectors
• Skin-to-skin contact is not important route of transmission
• ~50% have history of intimate contact
• Incubation: 2 to 40 y, generally 5 to 7 y

Tuberculoid Leprosy
• Initial hypopigmented macule well demarcated
• Later, lesions enlarge by peripheral spread, and margins
become elevated and circinate
• Central area becomes atrophic and depressed
• Lesions are densely anesthetic and devoid of normal skin
organs (sweat glands, hair follicles)
• Noncaseating granulomas with many lymphocytes and
Langhans' giant cells
• Invasion and destruction of nerves in the dermis by T cells
are pathognomonic for leprosy

8
 11/3/2019

Well-defined,
hypopigmented, slightly
scaling, anesthetic macules
and plaques Leprosy thigh demarcated
cutaneous lesions

Lepromatous Leprosy
• Initial erythematous papules or nodules
• Lesions coalesce, become symmetrically distributed
• Skin nodules, raised plaques, or dermal infiltration
• Late manifestations: loss of eyebrows + eyelashes,
pendulous earlobes, dry scaling skin
• Symmetric distal peripheral neuropathy and symmetric
nerve-trunk enlargement
• Signs and symptoms related to involvement of upper
respiratory tract, anterior chamber of the eye, and testes

9
 11/3/2019

Nodules and thick plaques on the dorsum on the fingers, wrists, and
forearms, with hypopigmentation of the overlying skin
Symmetry of involvement and loss of tissue of several finger tips

Multiple nodular skin lesions, particularly of

the forehead, and loss of eyebrows

10
 11/3/2019

Lepromatous Leprosy
• Dermatopathology is confined to the dermis and
particularly affects the dermal appendages
• Granulomas are absent
• Bacilli are numerous in skin and peripheral nerves, where
they initially invade Schwann cells, resulting in
degenerative myelination & axonal degeneration
• Bacilli are plentiful in circulating blood and in all organ
systems except the lungs and the CNS
• Patients are afebrile, and there is no evidence of major
organ system dysfunction

Complications
The Extremities
• Neuropathy leading to insensitivity and myopathy
• Insensitivity affects fine touch, pain, and heat receptors but
generally spares position and vibration appreciation
• Plantar ulceration, particularly at metatarsal heads, may
become secondarily infected and lead to adjacent cellulitis
and osteomyelitis

Peroneal nerve palsies

• Partial or complete footdrop

Loss of distal digits

• Consequence of insensitivity, trauma, secondary infection,
and profound osteolytic process

11
 11/3/2019

Complications
The Nose
• Bacillary invasion of the nasal mucosa can result in chronic
nasal congestion and epistaxis
• Destruction of the nasal cartilage, with consequent saddle-
nose deformity or anosmia
The Eye
• Corneal insensitivity resulting in trauma, secondary
infection, corneal ulcerations
• Anterior chamber is invaded by bacilli, may result in uveitis,
with cataracts and glaucoma
The testes
• May cause orchitis, impotency and infertility
Amyloidosis
• Secondary amyloidosis is encountered
• Abnormalities of hepatic and renal function

Diagnosis
• Characteristic skin lesions and histopathology
• Skin biopsies
• Diffuse hyperglobulinemia, may result in false-positive
serologic tests (e.g., VDRL, RA, ANA)
• On occasion, tuberculoid lesions may not
(1) appear typical
(2) be hypesthetic
(3) contain granulomas but only nonspecific lymphocytic
infiltrates
2 of 3 are considered sufficient for diagnosis

12
 11/3/2019

Treatment
• Dapsone, clofazimine, and rifampin
• Only rifampin is bactericidal
• Dapsone is generally safe, inexpensive
• Glucose-6-phosphate dehydrogenase deficiency who are
treated with dapsone may develop severe hemolysis

Antimicrobial Regimens Recommended for the Treatment of Leprosy in Adults

Form of Leprosy More Intensive Regimen WHO Recommended Regimen (1982)
Tuberculoid Dapsone (100 mg/d) for 5 Dapsone (100 mg/d, unsupervised) plus
(paucibacillary) years rifampin (600 mg/month, supervised) for 6
months
Lepromatous Rifampin (600 mg/d) for 3 Dapsone (100 mg/d) plus clofazimine (50
(multibacillary) years plus dapsone (100 mg/d), unsupervised; and rifampin (600
mg/d) indefinitely mg) plus clofazimine (300 mg) monthly
(supervised) for 1 year

13