Drug Resistance in Non-Tuberculous Mycobacteria

bronchocentric granulomatosis

A recent article in the Journal of Infection looks retrospectively at 13 years’ worth of clinical samples to identify pulmonary diseases caused by non-tuberculosis mycobacteria and to estimate what proportion of them were resistant to commonly used antimicrobials. Image credit: Martha L. Warnock, University of California, San Francisco. This image depicts a bronchiole that is almost completely occluded by granulomatous inflammation. Two small lumens remain (arrows). This lesion is frequent in non-tuberculous mycobacterial infections in the non-immunocompromised, where it may be associated with bronchiectasis. (Image credit)


There has been a rapid increase in the number of cases of infections caused by non-tuberculosis mycobacteria (NTM), especially due to the rise in the number of cases attributed to Mycobacterium avium intracellulare complex and Mycobacterium abscessus. In addition, there have been a deluge of cases of Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery, as well as reports of Mycobacterium fortuitum  group infections in patients receiving implantable cardioverter-defibrillator devices. (1,2) Naturally, with the growing concern of drug resistance, especially multi-drug resistance in Mycobacterium tuberculosis, it is but natural to want to understand if there is a similar risk profile for the NTM as well.

A 13 year retrospective study looking at longitudinal trends of isolates from pulmonary NTM infections was recently published in the Journal of Infection. (3) The authors report:

Culture results were obtained from 109,311 samples (31,758 subjects) of which 5960 samples (1209 subjects) isolated NTM over 13 years. Drug susceptibility results were obtained for 2637 NTM isolates (898 subjects). NTM isolation increased over time, driven by the Mycobacterium avium complex and Mycobacterium abscessus. Amongst most species, resistance to the key agents clarithromycin and amikacin was rare. The highest rate of resistance was found in M. abscessus and Mycobacterium simiae. Most M. abscessus isolates were sensitive to macrolides, aminoglycosides and tigecycline; M. simiae isolates were only consistently sensitive to clofazimine, amikacin and cycloserine.

Though the results are reassuring, for now, there needs to be cognizance of the fact that adding the issue of drug resistance would complicate an already difficult problem. It is a diagnostic challenge to have clinical suspicion of, and then establish the diagnosis of NTM. Irrational use of antimicrobials could easily add to the challenges of addressing these cases therapeutically by rendering the agents resistant.

References:

1. Kohler P, Kuster SP, Bloemberg G, Schulthess B, Frank M, Tanner FC, Rössle M, Böni C, Falk V, Wilhelm MJ, Sommerstein R, Achermann Y, Ten Oever J, Debast SB, Wolfhagen MJ, Brandon Bravo Bruinsma GJ, Vos MC, Bogers A, Serr A, Beyersdorf F, Sax H, Böttger EC, Weber R, van Ingen J, Wagner D, Hasse B. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015 Oct 21;36(40):2745-53. doi: 10.1093/eurheartj/ehv342. Epub 2015 Jul 17. PubMed PMID: 26188001.

2. Phadke VK, Hirsh DS, Goswami ND. Patient report and review of rapidly growing mycobacterial infection after cardiac device implantation. Emerg Infect Dis. 2016 Mar [February 29, 2016]. http://dx.doi.org/10.3201/eid2203.150584 DOI: 10.3201/eid2203.150584

3. Cowman S, Burns K, Benson S, Wilson R, Loebinger MR. The antimicrobial susceptibility of non-tuberculous mycobacteria. J Infect. 2016 Mar;72(3):324-31. doi: 10.1016/j.jinf.2015.12.007. Epub 2015 Dec 24. PubMed PMID: 26723913.

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