Drug treatment of pulmonary nontuberculous mycobacterial disease in HIV-negative patients: the evidence

Abstract

Pulmonary disease (PD) caused by nontuberculous mycobacteria is an emerging infection mainly in countries where the incidence of tuberculosis is in decline. It affects an elderly population, often with underlying chronic lung diseases, but its epidemiology shows significant regional variation. Guidelines and recommendations for treatment of these infections exist, but build strongly on expert opinion, as very few good quality clinical trials have been performed in this field. Only for the most frequent causative agents, the Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus, a reasonable number of trials and case series is now available. For the less frequent causative agents of pulmonary nontuberculous mycobacterial (NTM) disease (Mycobacterium xenopi, Mycobacterium malmoense, Mycobacterium fortuitum, Mycobacterium chelonae) data is mostly limited to a few very small case series. Within this review, we have collected and combined evidence from all available trials and case series. From the data of these trials and case series, we reconstruct a more evidence-based overview of possible drug treatment regimens and their outcomes.

Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin

“…Its main clinical use so far is in the multidrug treatment of leprosy and multidrugresistant tuberculosis (18). For the treatment of MAC pulmonary disease, a clofazimine-ethambutol-macrolide regimen was suggested to be as effective as a rifampin-ethambutol-macrolide reg- imen (2,19). Our in vitro results support the role of clofazimine for the treatment of M. avium disease, as we found synergistic effects between clofazimine and amikacin or clarithromycin.…”

“…Treatment outcomes are generally poor, and current treatment recommendations have a very limited evidence base, since very few clinical trials have been performed (1,2).…”

“…One of the promising combinations is amikacin and clofazimine, given the key role of amikacin in the treatment of NTM infections (2,3) and the unique characteristics of clofazimine, like its prolonged half-life, its preferential accumulation inside macrophages (4), and the recently found bactericidal activity only after 2 weeks of treatment in the mouse model of tuberculosis (5).…”

Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria

“…Diagnosis of NTM-PD can be difficult, and if it is treated, the outcomes are relatively poor. Rates of treatment failure differ by species but may range from 5% (M. kansasii) to 50% (M. abscessus or fibrocavitary M. avium complex isolates) (537). Molecular typing of NTM to assess virulence (i.e., the chance that the isolate signifies a true NTM-PD isolate) or to predict the response to treatment has thus been of significant interest.…”

New Insights in the Treatment of Nontuberculous Mycobacterial Pulmonary Disease

“…On average, 50 (M. abscessus) to 70% MAC patients who tolerate recommended regimens achieve prolonged culture conversion [2]. This grave situation has recently led to a series of clinical and preclinical studies aiming to optimize antibiotic treatment of NTM pulmonary disease (NTM-PD).…”