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.

Keywords::

• atypical mycobacteria
• lung disease
• Mycobacterium abscessus
• Mycobacterium avium complex
• nontuberculous mycobacteria

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The incidence and prevalence of non-tuberculous mycobacteria pulmonary disease (NTM-PD) increases in many regions, particularly in areas with low tuberculosis prevalence.

• • In most areas, Mycobacterium avium complex (MAC) bacteria are the most frequent causative agents of NTM-PD, followed by Mycobacterium kansasii, Mycobacterium xenopi and Mycobacterium abscessus in area-specific order.

• • Available treatment recommendations have a very limited evidence base, as very few trials have been performed.

• • The efficacy of currently recommended treatment regimens differs strongly between studies/populations, which may be related to the relative frequency of cavitary disease.

• • The outcomes of treatment differ between species, with particularly poor outcomes in disease caused by M. xenopi, M. simiae and M. abscessus.

• • Pulmonary diseases caused by M. abscessus are hardest to treat and treatment regimens for these diseases have the smallest evidence base.

• • In vitro-in vivo discrepancies make that in vitro drug susceptibility data offers very little support to optimize treatment regimens in individual patients, with the macrolides as possible exceptions.

• • In vivo pharmacokinetic (PK) data and in vitro simulations suggest that doses of many drugs in current regimens may be too low to be effective.

• • The lack of good quality clinical trials is the single most important impediment to progress in treating these very serious infections.