Mycobacterium avium Complex

The designation Mycobacterium avium complex (MAC) primarily included the two species M. avium and M. intracellulare, which are among the most important and widespread pathogenic non-tuberculous mycobacteria (NTM). These species can be distinguished from each other biochemically and morphologically only with very sophisticated methods.

Recently, the MAC complex has been defined as a grouping of slow-growing mycobacteria based on molecular biology criteria. Members of this complex should have corresponding levels in at least two of the following targets against either M. avium ATCC 25291T or Mycobacterium intracellulare ATCC 13950T:

• >99.4 % sequence identity for the full 16S rRNA gene, >98.7 % for the partial (5') 16S rRNA gene, >97.3 % for hsp65 and >94.4 % for rpoB region V.
• A >97. 5% value in concatenated analyses of >2500 bp encompassing 16S rRNA, hsp65, and rpoB gene sequence data or ≥85% average nucleotide identity with M. avium ATCC 25291T or M. intracellulare ATCC 13950T based on whole-genome sequencing data is recommended.

According to this molecular definition, the MAC complex currently consists of 12 validly published species (van Ingen J et al. 2018):

• Mycobacterium avium
• Mycobacterium intracellulare
• Mycobacterium chimaera
• Mycobacterium colombiense
• Mycobacterium arosiense
• Mycobacterium vulneris
• Mycobacterium boucheduronense
• Mycobacterium timonens
• Mycobacterium marseillnse
• Mycobacterium yongoense
• Mycobacterium paraintracellulare
• Mycobacterium lepraemurium.

M. avium avium is typically detected in birds, and the closely related subspecies M. avium silvaticum is predominantly detected in woodpigeons (Dhama K et al. 2011; Sweeney RW et al. 2012).

M. avium paratuberculosis is the infectious agent of "Johne's disease" in ruminants. This strictly host-associated subspecies is not normally found in the environment. However, infected cows can excrete enormous amounts of the organism and thus infect other animals. A causal involvement of M. avium paratuberculosis in Crohn's disease in humans is controversially discussed.

For clinically severe disease, therapy with daily administration at the following dosages is recommended (Griffith DE et al. 2007):

• Clarithromycin 1000 mg or Azithromycin 250 mg
• plus
• Rifampicin 600 mg or rifabutin 300 mg
• plus
• Ethambutol 15 mg/kg

In contrast, for clinically moderate disease (nodular and bronchiectatic radiographic manifestations), (Griffith DE et al 2007) recommends intermittent therapy on weekly 3 days with the following doses:

• Clarithromycin 1000 mg or Azithromycin 500 mg
• plus
• rifampicin 600 mg or rifabutin 300 mg
• plus
• Ethambutol 25 mg/kg

Treatment with rifabutin instead of RMP, which was recommended in the 1990s, was ultimately not convincing because the side effect rate of rifabutin in combination treatment is high (mainly uveitis and leukopenia) and the clinical superiority despite higher tissue concentrations and at the same time low inhibitory concentrations in vitro compared with RMP could not be proven (Griffith DE et al. 2007). An exception is concurrent antiretroviral and antifungal treatment of AIDS patients, for which rifabutin should be preferred due to pharmacological interactions between viral drugs and rifamycins.

The addition of SM/amikacin as a fourth drug may be considered in severe and extensive cavernous M. avium infections for more rapid bacterial count reduction (Griffith DE et al 2007). Other effective agents that may be considered in cases of intolerance to other drugs or macrolide resistance include moxifloxacin, although this has shown some antagonism to clarithromycin in animal studies, and protionamide, although there is only empirical data on this, similar to the closely related agent ethionamide. Clofazimine is also considered an alternative (Griffith DE et al. 2007).

The duration of treatment - with good clinical success - depends, among other things, on the microbiological findings. The aim should be to continue therapy until sputum cultures have remained negative for more than 12 months. This usually results in therapy periods of 18 months (Griffith DE et al. 2007).

MAC isolates are frequently found in the environment, e.g., in tap water. The detection of MAC especially from bronchopulmonary samples must therefore be questioned very critically for its clinical significance.

1. Griffith DE et al (2007) Am J Respir Crit Care Med 175: 367-416.