Nontuberculous mycobactera (NTM) is a collective term for all Mycobacterium spp. that are not part of the Mycobacterium tuberculosis complex or Mycobacterium leprae. Virtually all are environmental mycobacteria (rather than  the human- and animal-adapted pathogens that cause tuberculosis and leprosy), although they are able to cause human infection in a limited number of situations, i.e. when the human is immunocompromised because of therapy or diseases such as cancer or HIV; or when they are accidentally introduced into the body through surgery, or contaminated needles. Rapidly growing mycobacteria (RGM) are a subset of NTM that – as the name suggests – grow faster than Mycobacterium tuberculosis complex. Which still means that these organisms will take 1-2 weeks to grow out on culture media (the TB germ usually takes 3-6 weeks to grow to a sufficient quantity to be detected by the automated mycobacterial culture systems that most laboratories in developed countries use nowadays) rather than the 1-2 days it takes for most other pyogenic bacteria to grow.

Most RGM infections are difficult to treat – more so than tuberculosis – because:

  1. Like tuberculosis, a combination of drugs are required for serious or deep-seated infections.
  2. But unlike tuberculosis, some of the initial antimicrobial agents – used for the first 1-2 months – are intravenous antibiotics rather than oral antibiotics.
  3. Treatment duration is usually months longer than conventional tuberculosis therapy (which is usually 6 months).

It is a good thing that they are far less virulent compared to tuberculosis and seldom cause infections in humans.

For quite a number of years now, I have had the impression that these RGM are becoming more and more resistant to the antibiotics used to treat them, although there is logically no clear explanation for this phenomenon: unlike other types of pyogenic bacteria (or even tuberculosis), infections are relatively uncommon hence RGM are collectively less exposed to antimicrobial agents compared to other pyogenic bacteria. But this impression seems to be correct. After looking through 6 years (2006-2011) of clinical culture results (427 isolates in total) from the only two clinical mycobacterial culture laboratories in Singapore (Singapore General Hospital Central Tuberculosis Laboratory and National University Hospital Microbiology Laboratory), we found that Mycobacterium abscessus and Mycobacterium fortuitum – the two most common RGM causing infection here and elsewhere in the world – were becoming more resistant to linezolid (M. abscessus) as well as imipenem and clarithromycin (M. fortuitum) even just over this short period of time. The situation isn’t quite as bad as – say – with carbapenem-resistant Enterobacteriaceae, but ti does mean that therapeutic options for these infections continue to diminish over time.

Breakdown of RGM species (left) and decreasing susceptibility to linezolid in M. abscessus over time (right)

Breakdown of RGM species (left) and decreasing susceptibility to linezolid in M. abscessus over time (right). Images courtesy of Ms. Sarah Tang.

This work is now published online in the European journal Clinical Microbiology and Infection (corrected proof only at this stage), but behind the Elsevier pay wall – so here’s the link to the abstract. The majority of the 427 isolates were from lower respiratory tract samples (64.9%; mostly from patients with chronic obstructive lung disease), with the rest from cutaneous abscesses/infections (9.8%) or blood (8.4%; many were from intravenous drug abusers).

Now, these results and the paper would have just remained a daydream if not for the dedication and hard work of Ms Sarah Tang, an infectious diseases pharmacist from SGH (she doesn’t have her employee profile online, unlike the senior doctors and staff of that hospital) who is rightly the first and corresponding author on the paper. She began the project from scratch during her 1-year infectious diseases pharmacy residency program, obtaining the culture results from both SGH and NUH labs, meticulously combing through the clinical records (both online and hardcopy notes) of 427 patients, performing the statistical analysis on drug resistance rates, and then writing up the paper and dealing with the reviewers’ and editors’ comments. I can think of very few doctors who can manage what she has done, which is on top of her usual pharmacist work and resident learning. “Clinician-scientist” should not be equivalent to just “doctor-scientist”.

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Join the conversation! 3 Comments

  1. Li Yang, thank you for posting the abstract’s URL and your above comments on this venue. As the Empire is in decline and the medical profession here has abdicated/exchanged its authoritative role for …?, I have limited access into the halcyon fields of Elsevier’s mother lode of knowledge. Were the MIC’s obtained all via broth microdilution during the span in question? Were results all quantitative as in your linezolid data or qualitative and impacted by the sometimes-moving breakpoints during that time frame? Is linezolid being used much now in the community or for MTb salvage regimens? I don’t recall much institutional promiscuous use during my last tour of duty. If not, why the decline?
    祝你成功你的家人在你的事业和幸福!
    David

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    • How curious to have a comment by you on this site, David! You may be more appeased to learn that academics at the rising university of the East also have no access to this journal via Elsevier… All MICs were obtained via broth microdilution, and the results are therefore all quantitative (rather than arbitrary breakpoints that may not mean very much when it comes to treatment for RGM infections). And you are right, linezolid is still very rarely used in Singapore, hence we can’t explain the MIC rise over time in RGMs where this drug is concerned. Perhaps the ribosomal mutation(s) occurred for another reason and just incidentally affected the linezolid target site. Gong xi fa cai, by the way!

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  2. […] raised regarding the prevalence of rapidly-growing mycobacteria (RGM) in Singapore following the previous post. Researchers in several countries have found that the prevalence of infections caused by RGM had […]

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Antimicrobial resistance, Public Health

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