Current Opinions in the Treatment of Pulmonary Nontuberculous Mycobacteria in Non-Cystic Fibrosis Patients: Mycobacterium abscessus Group, Mycobacterium avium Complex, and Mycobacterium kansasii

Abstract

Treatment of pulmonary infections caused by Mycobacterium avium complex (MAC) and Mycobacterium kansasii involves multidrug oral therapy with a macrolide (azithromycin or clarithromycin), ethambutol, and a rifamycin (rifampin or rifabutin). Patients with M. kansasii rapidly respond to a regimen of intermittent (three times weekly) or daily administration of this three-drug regimen. Patients with MAC respond more slowly and often require adjustment of the multidrug regimen because of drug intolerance. The usual treatment for patients with MAC nodular disease takes 15–18 months, with a goal of 12 months of negative cultures. Recent studies support the use of a three-times weekly oral treatment regimen for patients with macrolide-susceptible nodular MAC disease. Patients with upper lobe fibro-cavitary MAC, macrolide-resistant MAC, or severe nodular bronchiectatic disease are usually treated with a daily multidrug regimen supplemented with an injectable antibiotic (amikacin or streptomycin) or, most recently, inhaled preparations of amikacin. Patients with cavitary changes and/or those with macrolide-resistant isolates are often associated with poor treatment response and may require surgical resection in addition to their drug therapy. In contrast to patients with lung disease due to MAC and M. kansasii, the presence of a functional erythromycin ribosomal methylase (erm) gene in the majority of isolates of Mycobacterium abscessus (M. abscessus subsp. abscessus) blocks the activity of macrolides and precludes an effective oral drug regimen for most of these patients. Treatment regimens for macrolide-resistant M. abscessus require long-term intravenous access and parenteral drug combinations of amikacin, cefoxitin, imipenem, and/or tigecycline. Because of the inconvenience of dosing cefoxitin, a regimen of imipenem and amikacin may be preferred. Cure with these agents is infrequent because of the long-term toxicity and expense of these agents. Other treatment options are currently dismal. The role of newer antimicrobials such as tedizolid and bedaquiline has not been evaluated. Approximately 15 % of isolates of subsp. abscessus and all isolates of subsp. massiliense (infrequent in the USA) have a nonfunctional erm gene and are macrolide susceptible, making an oral macrolide an important treatment component and increasing the likelihood of long-term cure of the infection.