Treatment of Mycobacterium avium Complex (MAC)

Abstract

complex (MAC) is the most commonly isolated nontuberculous mycobacterial respiratory pathogen worldwide. MAC lung disease is manifested either by fibrocavitary radiographic changes similar to pulmonary tuberculosis or by bronchiectasis with nodular and reticulonodular radiographic changes. This latter form of MAC lung disease, termed "nodular bronchiectatic (NB) MAC lung disease" is the most common form of MAC lung disease in the United States. Treatment at the time of diagnosis is always indicated for fibrocavitary MAC lung disease because it is always progressive and associated with increased morbidity and mortality compared with NB MAC lung disease. In contrast, the NB form of MAC lung disease is more indolent and frequently does not require antimycobacterial therapy. For patients with NB MAC lung disease, the priorities are typically to treat the underlying bronchiectasis and determine the course and impact of the MAC infection over time. Guidelines-based MAC therapy with multidrug regimens including macrolides is usually effective, but far from as predictably effective and durable as therapy for tuberculosis. It is imperative that clinicians are familiar with MAC drug resistance mechanisms and the pitfalls of inappropriate dependence on in vitro drug susceptibility testing which can predispose patients to the development of macrolide resistance with its attendant high mortality. It is now more than 20 years since the emergence of macrolides for MAC therapy with no new comparably effective agents introduced in that time, although one new inhaled amikacin therapy under study offers promise.

GenoType NTM-DR Performance Evaluation for Identification of Mycobacterium avium Complex and Mycobacterium abscessus and Determination of Clarithromycin and Amikacin Resistance

“…abscessus and M. abscessus subsp. bolletii due to induced synthesis of an RNA methylase encoded by the erm (41) gene (36). M. abscessus subsp.…”

“…The regions of genes involved in CLR and AMK resistance were evaluated by PCR and sequencing as described previously (20)(21)(22). Each M. abscessus isolate was genotyped for the presence of a T-to-C mutation at position 28 of the erm (41) gene, a mutation associated with loss of inducible macrolide resistance (20). The presence of point mutations at position 2058 or 2059 (Escherichia coli numbering) in the rrl gene was also investigated (21).…”

“…The NTM-DR assay also allows for detection of antibiotic resistance to macrolides and aminoglycosides. Specifically, macrolide resistance is identified by polymorphisms (T28 or C28) at position 28 in the erm (41) gene and mutations at positions 2058/2059 in the rrl gene (11). Likewise, aminoglycoside resistance is detected by examining positions 1406 to 1408 of the rrs gene (10,11).…”

“…The aim of this study was to evaluate the analytical and clinical performance of the NTM-DR assay for identifying (sub)species of MAC and M. abscessus and determining their resistance to macrolides and aminoglycosides. We evaluated the performance of the assay by comparison of the results to those with multigene sequence-based identification, BMD for clarithromycin (CLR) and amikacin (AMK), and sequencing of the erm (41), rrl, and rrs genes.…”

Repositioning rifamycins for Mycobacterium abscessus lung disease

“…As an FDA-approved drug that is already used to treat TB [66] and MAC [67], rifabutin is a compelling repurposing candidate against M. abscessus. Indeed, a rifamycin would be a welcome addition to the M. abscessus treatment regimen, as this drug class is bactericidal and active against mycobacterial persister subpopulations [46].…”