Nontuberculous Mycobacteria

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Chapter 209 Nontuberculous Mycobacteria

Nontuberculous mycobacteria (NTM), also referred to as atypical mycobacteria or mycobacteria other than tuberculosis (MOTT), are members of the family Mycobacteriaceae and the genus Mycobacterium. Genetically, NTM constitute a highly diverse group of bacteria that differ from Mycobacterium tuberculosis complex bacteria in their pathogenicity, nutritional requirements, ability to produce pigments, enzymatic activity, and drug-susceptibility patterns. In contrast to the M. tuberculosis complex, NTM are acquired from environmental sources and not by person-to-person spread. Their omnipresence in our environment implies that the clinical relevance of NTM isolation from clinical specimens is often unclear; a positive culture might reflect contamination rather than true NTM disease. NTM are associated with pediatric lymphadenitis, otomastoiditis, serious lung infections, and, albeit rarely, disseminated disease. Treatment is long-term and cumbersome and often requires adjunctive surgical treatment. Guidelines on diagnosis and treatment are provided by the American and British Thoracic Societies.

Etiology

NTM are ubiquitous in the environment all over the world, existing as saprophytes in soil and water but also as opportunistic pathogens in animals, including swine, birds, and cattle. Many of the 130 validly published NTM species have been isolated from environmental and animal samples, implying that humans are constantly exposed to NTM from the environment, for instance during showering. Owing to the introduction of molecular identification tools such as 16S rDNA gene sequencing, the number of identified NTM species has grown to more than 130; the clinical relevance (i.e., the percentage of isolates that are causative agents of true NTM disease, rather than contamination) differs significantly by species.

In the USA, M. avium-intracellulare complex (MAC) and M. kansasii are most often isolated from clinical samples, yet the isolation frequency of these species differs significantly by geographical area. MAC bacteria have been commonly isolated from natural and synthetic environments in the USA, and cases of MAC disease have been successfully linked to home exposure to shower and tap water. Although the designation M. avium suggests that M. avium infections are derived from birds (avium being Latin for “of birds”), molecular typing has pointed out that M. avium strains that cause pediatric lymphadenitis and adult pulmonary disease represent the M. avium hominissuis subgrouping that is mainly found in humans and pigs and not in birds.

Some NTM have well-defined ecologic niches that help explain infection patterns. The natural reservoir for M. marinum is fish and other cold-blooded animals, and hence infections due to M. marinum follow skin injury in an aquatic environment. M. fortuitum complex bacteria and M. chelonae are ubiquitous in water and have caused clusters of nosocomial surgical wound and venous catheter–related infections. M. ulcerans is associated with severe, chronic skin infections (Buruli ulcer disease) and is endemic mainly in West Africa and Australia, although other foci exist. Its incidence is highest in children <15 yr old. Mycobacterium ulcerans had been commonly detected in environmental samples by polymerase chain reaction (PCR) but was only recently recovered by culture from a Water Strider (Gerris sp.) from Benin.

Clinical Manifestations

Lymphadenitis of the superior anterior cervical or submandibular lymph nodes is the most common manifestation of NTM infection in children (Table 209-1). Preauricular, posterior cervical, axillary, and inguinal nodes are involved occasionally. Lymphadenitis is most common in children 1-5 yr of age and has been related to their tendency to put objects contaminated with soil, dust, or standing water into their mouths. Given the constant environmental exposure to NTM, the occurrence of these infections might also reflect an atypical immune response of a subset of the infected children during or after their first contact with NTM.

Table 209-1 DISEASES CAUSED BY NONTUBERCULOUS MYCOBACTERIAL SPECIES

CLINICAL DISEASE COMMON SPECIES LESS-COMMON SPECIES
Cutaneous infection M. chelonae, M. fortuitum, M. abscessus, M. marinum M. ulcerans*
Lymphadenitis MAC M. kansasii, M. haemophilum, M. malmoense
Otologic infection M. abscessus, MAC M. fortuitum
Pulmonary infection MAC, M. kansasii, M. abscessus M. xenopi, M. malmoense, M. szulgai, M. fortuitum, M. simiae
Catheter-associated infection M. chelonae, M. fortuitum M. abscessus
Skeletal infection MAC, M. kansasii, M. fortuitum M. chelonae, M. marinum, M. abscessus, M. ulcerans*
Disseminated MAC M. kansasii, M. genavense, M. haemophilum, M. chelonae

MAC, Mycobacterium avium complex.

* Not endemic in the USA.

Found primarily in Northern Europe.

From American Academy of Pediatrics: Red book: 2009 report of the Committee on Infectious Diseases, ed 28, Elk Grove Village, IL, 2009, American Academy of Pediatrics, p 703.

Affected children usually lack constitutional symptoms and present with a unilateral subacute and slowly enlarging lymph node or group of closely approximated nodes >1.5 cm that are firm, painless, freely movable, and not erythematous (Fig. 209-1). The involved nodes occasionally resolve without treatment, but most undergo rapid suppuration after several weeks (Fig. 209-2). The center of the node becomes fluctuant, and the overlying skin becomes erythematous and thin. Eventually, the nodes rupture and form cutaneous sinus tracts that drain for months or years, resembling the classic scrofula of tuberculosis (Fig. 209-3).

In the USA, M. avium complex accounts for approximately 80% of NTM lymphadenitis in children. Birds are an unlikely source of these M. avium complex infections, as molecular typing has shown that the lymphadenitis-associated M. avium bacteria are of the human or porcine subtype rather than the bird type. M. kansasii accounts for most other cases of lymphadenitis in the USA. M. malmoense and M. haemophilum are described. The former is only common in northwestern Europe; for the latter, underestimation is likely because the bacteria require specific culture conditions (hemin-enriched media, low incubation temperatures). On the basis of PCR analysis of lymph node samples from lymphadenitis cases in the Netherlands, M. haemophilum was the second most common cause of this infection after M. avium complex.

Cutaneous disease caused by NTM is rare in children (see Table 209-1). Infection usually follows percutaneous inoculation with fresh or salt water contaminated by M. marinum.

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