the mycobacterium avium complex and slowly growing mycobacterium

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The Mycobacterium avium Complex and Slowly Growing Mycobacteria

Dr. milad shahini

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DISEASES OF NON-TUBERCULOUS MYCOBACTERIA

The genus Mycobacterium is routinely divided into two group:

Slowly growing mycobacteria (7 days to form colonies)

Rapidly growing mycobacteria (3 days to form colonies)

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NTM infection is from environmental sources:

o Natural waterso Drinking watero Household plumbingo Soils NTM are not contaminants in soils and drinking water, they grow

in those habitats. Human infection occurs by inhaling dusts from soils and

aerosols from water

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NTM diseases:

Pulmonary infection Sinusitis and otitis media Nosocomial infections associated with surgical interventions Cervical lymphadenitis in young children (18 months to 5

years) Bacteremia in individuals with compromised immune

systems

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NTM PULMONARY DISEASE

There are two clinical presentations for pulmonary NTM infection

Disease associated with cavitary lesions Disease associated with bronchiectasis

• Cough• weakness• night sweats

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NTM SINUSITIS AND OTITIS MEDIA

Recently it has been shown that cases of chronic rhinosinusitis are due to mycobacterial infections

Both rapidly and slowly growing Mycobacterium spp Rare

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MYCOBACTERIAL CERVICAL LYMPHADENITIS IN CHILDREN

Mycobacterial-associated cervical lymphadenitis is exclusively caused by M.avium.

The majority of cases are in 18-month to 5-year-old children. The first sign of infection is swollen lymph nodes in the head

or neck, often limited to one side. Infection occurs via oral ingestion of water or soil containing

M.avium. Surgical excision of the infected lymph node is the

recommended treatment.

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BACTERAEMIA IN IMMUNODEFICIENT OR IMMUNOSUPPRESSED INDIVIDUALS

Individuals that are immunodeficient due to HIV infection are much more susceptible to NTM infection.

In HIV-infected individuals, M. avium (87%) is by far the predominant pathogen.

Infection is manifest as an M. avium bacteraemia (up to 100 000 CFU/ml) and even higher numbers (10 000 000 CFU/g) in tissue.

Risk factors for M. avium infection in the HIV-infected include:o consumption of spring watero consumption of raw fisho showering outside the home

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DEVICE- AND HOSPITAL-ACQUIRED INFECTIONS

Due to the presence of slowly growing NTM in drinking water and their relative resistance to high temperature and disinfectants, device-associated, pseudo-infections have been associated with NTM. These present as outbreaks of NTM infection associated with a medical procedure; for example, the use of bronchoscopes or catheters.

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DIFFERENTIAL DIAGNOSIS OF NTM INFECTION

One of the emerging and challenging aspects of NTM disease is to determine its prevalence in countries with a high tuberculosis (TB) burden, such as Latin America and India

In such regions, the proportion of citizens with access to treated water is increasing

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In countries with a high TB burden, where treated and untreated water are both available, pulmonary mycobacteriosis could be caused by either M. tuberculosis or by an NTM species.

Both fibronocular (32%) and cavitary (68%) disease were seen amongst such patients and 33% of the patients were infected with M. kansasii, 30% with M. avium complex, and 20% with M. abscessus and M. fortuitum

DIFFERENTIAL DIAGNOSIS OF NTM INFECTION

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LABORATORY DIAGNOSIS OF NTM INFECTION

The gold standard for detection of NTM infection is culture.o Rapidly growing mycobacterial species form colonies by 3 days on

agar-based complex mediao Slowly growing species require 7-10 days or longer on agar-based

complex media

o 16S rRNAo rRNA internal transcribed sequence (ITS)o Hsp65o rpoB

An alternative to culture is PCR-based amplification of genus- or species specific sequences

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MYCOBACTERIUM AVIUM COMPLEX

The MAC currently consists of: four subspecies:

Seven species:

I. Mycobacterium chimaera

II. M. colombiense

III. M. marseillense

IV. M. timonense

V. M. bouchedurhonense

VI. M. ituriense

VII. M.arosiense

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M. avium subsp. hominissuis, M. intracellulare and M. chimaera are the only human pathogens.

M. avium subspecies paratuberculosis, the causative agent of Johne’s disease in cattle is also the aetiologic agent of Crohn’s disease in humans.

It has been shown that, unlike M. avium, M. intracellulare is not found in drinking water.

Isolates from drinking water and plumbing biofilms have been shown to be exclusively M. chimaera

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MAC organisms show a characteristic heterogeneous colony morphology (Figure Small translucent (smooth transparent (SMT)) colonies usually co-occur with glossy, whitish colonies (smooth domed (SMD)).

SMT bacteria have greater potential for intracellular multiplication in macrophages, have greater virulence in animal models, and are more resistant to antibiotics than SMD bacteria

Middlebrook 7H10 agar.

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A variety of methods are available for identifying and fingerprinting members of the M.avium complex:


1. Typing using mycobacterial interspersed repeat unit-variable number tandem repeat (MIRU-VNTR)

2. Pulsed-field gel electrophoresis (PFGE)3. Repetitive sequenced-based PCR (rep-PCR)4. Insertion sequence restriction fragment length polymorphism (IS-

RFLP)

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MYCOBACTERIUM KANSASII

M.kansasii forms visible niacin-negative, photochromogenic colonies on LJ slants at 2–3 weeks After 2 weeks in ambient light, the colonies turn bright yellow or orange.

M.kansasii causes pulmonary disease, cutaneous infections , and disseminated disease (bacteraemia).

Disseminated disease is usually restricted to immunodeficient individuals or those infected with HIV

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MYCOBACTERIUM MARINUM

M.marinum is a photochromogenic species with an optimal growth temperature of 25–35C

It is most commonly associated with a superficial cutaneous infection sometimes referred to as ‘swimming pool granuloma’ or ‘fish-tank granuloma’.

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MYCOBACTERIUM MARINUM

Superficial infections usually heal spontaneously, but the course is very prolonged and associated with discomfort.

Further extension to regional lymph nodes and systemic infection does usually not occur because of the low temperature required for optimal growth.

Antibiotic treatment was generally successful (87%), but in a number of cases standard antibiotic therapy was changed to antimycobacterial therapy. Without prompt treatment, the superficial infection spread to deeper tissues (29%), where chemotherapy failure was more common and surgical intervention required.

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MYCOBACTERIUM XENOPI

• Strains of this species require 6–8 weeks to form visible, very fine, round colonies on primary isolation.

• M.xenopi is resistance to heat and high optimum temperature for growth, The optimum growth temperature for the species is 45C.

• Rifamycin-containing regimens were the most successful for treatment, while clarithromycin containing regimens were less effective.

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MYCOBACTERIUM MALMOENSE

• Even amongst the slowly growing mycobacteria, M.malmoense is even slower; it takes more than 6 weeks for colonies to form on agar-based media.

• Growth rate is improved by reducing the pH to 6 and adding pyruvate to standard mycobacterial media.

• Infection sites include the lung, skin, lymph nodes (cervical lymphadenitis) and bursae.

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MYCOBACTERIUM HAEMOPHILUM

• M.haemophilum infections may be under recognized because of the predilection of this species for a low incubation temperature (30C) and its unique requirement for ferric ammonium citrate or hemin for growth.• M.haemophilum commonly presents as disseminated cutaneous, ulcerating lesions in individuals with some form of immunodeficiency,

the mycobacterium avium complex and slowly growing mycobacterium

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