MDR-TB Treatment & Prevention

For identification of NTM (MOTT)either the Genotype (Hain test) for NTM or classical biochemical test can help for identification. But the latter method take a long time. If you isolate more than 1 time, it's a significant to further study and I knew from clinician that no need for treatment of NTM infection and no trasmission to other person.

Hi Vivian and thanks for this question; when I was supporting the MSF project in Shiselweni, we came across a few such cases; the issue at that time was that there was often 1 culture, or the identification was done after the SLD had been started.
Regarding the treatment of MOTT, it actually depends on the subspecies, a result we cannot get in Swaziland; if confirmed obviously, the treatment for MAC is Clarithro, or Azithro (caction with its use as per the recent FDA warning) + Ethambuthol + Rifabutine; the issues with Rifabutine are: 1. Its cost; 2. if the patient is HIV+, the interactions with the NNRTIs and the PI, needing dose adjustment. just as an info most of the cases where a pulmonary MOTT is confirmed, we need to also check all the reticular- endothelial system and look (between other things) at the FBCs and LFT; should there be a ERS involvement, it is almost sure that the patient has very low CD4 (<50/ml), therefore ART should be expedited.
If the rate of MOTT is high (should be less than 1% of the mycobacteria isolated in sputum smears cultures) we may question 1. the local epidemiology (MOTT are most ...

Hi Vivian and thanks for this question; when I was supporting the MSF project in Shiselweni, we came across a few such cases; the issue at that time was that there was often 1 culture, or the identification was done after the SLD had been started.
Regarding the treatment of MOTT, it actually depends on the subspecies, a result we cannot get in Swaziland; if confirmed obviously, the treatment for MAC is Clarithro, or Azithro (caction with its use as per the recent FDA warning) + Ethambuthol + Rifabutine; the issues with Rifabutine are: 1. Its cost; 2. if the patient is HIV+, the interactions with the NNRTIs and the PI, needing dose adjustment. just as an info most of the cases where a pulmonary MOTT is confirmed, we need to also check all the reticular- endothelial system and look (between other things) at the FBCs and LFT; should there be a ERS involvement, it is almost sure that the patient has very low CD4 (<50/ml), therefore ART should be expedited.
If the rate of MOTT is high (should be less than 1% of the mycobacteria isolated in sputum smears cultures) we may question 1. the local epidemiology (MOTT are most often found in the soil), 2. the internal and external quality assurance of the NRL (which should be excellent as the organization I am working for now is involved in this particular aspect and I remember from 2008 that there used to be a MSF lab tech who was supporting this component of the lab.
I wish this helps, the challenge here is really the Rifabutine, i am not sure it is on the Swaziland EDL maybe if you have few cases, you may find it in Nelspruit???
Please give us some follow up, it is always appreciated.
Francoise

2+ positive cultures does increase to probability that the MOTT is a real pathogen. If these are sputum culture results and there is pulmonary disease on chest x-ray then I would consider M kansasii and MAI as the most likely pathogenic species (obviously lots on MOTT species can be associated with disease in HIV). Radiographic findings can be helpful with M kansasii classically causing thin walled cavitary lesions and MAI consolidations and nodular infiltrates. If you add on risk factors - MAI being most common at CD4 <50-100 that may help. Obviously M kansasii also occurs at that CD4 count. Gold mine workers (including retired/retrenched who have left SA and returned to SD tend to have more M kansasii than other population groups. If the MOTT is growing in the blood and the CD4 count is <50, it will be MAI most of the time and I would treat for that with azithromycin and ethambutol. We generally also add rifampicin or rifabutin if the disease burden is very high (the ethambutol and rif reduce the risk of developing macrolide resistance and may reduce time to sterilizing blood cultures). Obviously immune restoration is the critical component.

Hope you all well.
Firstly my advise to you vivien is that you should use the Hain genotype CM assay for identification of MOTT or NTM. We are currently using it in our lab and it is working well.
Secondly, i share in your curiosity as to what clinicians do with these results. What i know for sure is that there are some MOTT infections going round that require attention. We have sometimes isolated and identified the same MOTT from 2 specimens from the same individual. Furthermore, these individuals present with Symptoms consistent with TB hence their being
refered for TB diagnosis.

There are 3 potential sources of mycobacteria in a culture - environmental contamination, commensal and pathogenic. It is possible to get repeated cultures of commensal mycobacteria. Disease caused by MOTTS is often very difficult to treat as they can be naturally resistant to TB drugs.

The microbiologists (or molecular biologists) and the treating clinician should be in close communication. Microbiologists should not be making judgments without understanding the clinical picture and vice versa.

For the lab it appears that the rush to the new expensive technologies has left some useful skills behind.
ZN microscopy can be useful for differentiating mycobacteria.
Similarly culture on LJ is useful (the colonies look different).

Unfortunately the GeneXpert only picks up TB complex, leaving other infections undiagnosed. Roche in South Africa have developed a PCR that tests for TB, avium and kansasii – the main pulmonary mycobacterial pathogens in that part of the world.

The line probe assays (such as the Hain test) are prone to amplicon contamination and need specialist training and facilities such as PCR clean rooms. When WHO endorsed the line probe technology for DR testing it included a long list of recommendations on how they should be used. http://www.who.int/tb ...

There are 3 potential sources of mycobacteria in a culture - environmental contamination, commensal and pathogenic. It is possible to get repeated cultures of commensal mycobacteria. Disease caused by MOTTS is often very difficult to treat as they can be naturally resistant to TB drugs.

The microbiologists (or molecular biologists) and the treating clinician should be in close communication. Microbiologists should not be making judgments without understanding the clinical picture and vice versa.

For the lab it appears that the rush to the new expensive technologies has left some useful skills behind.
ZN microscopy can be useful for differentiating mycobacteria.
Similarly culture on LJ is useful (the colonies look different).

Unfortunately the GeneXpert only picks up TB complex, leaving other infections undiagnosed. Roche in South Africa have developed a PCR that tests for TB, avium and kansasii – the main pulmonary mycobacterial pathogens in that part of the world.

The line probe assays (such as the Hain test) are prone to amplicon contamination and need specialist training and facilities such as PCR clean rooms. When WHO endorsed the line probe technology for DR testing it included a long list of recommendations on how they should be used. http://www.who.int/tb/features_archive/policy_statement.pdf

There was a nice book produced a few years ago. Practical Handbook for the Phenotypic and Genotypic Identification of Mycobacteria. I’m not sure it is still in print but sections can be found by googling the title of the book and the various section headings. http://www.esmycobacteriology.eu/PDF%20files/foreword.pdf

In some parts of the world MOTTS are more common pathogens than Mtb. and there is a lot of expertise in Europe and Latin America. e.g. the Mycobacteria Reference Laboratory at the National Institute for Public Health and the Environment (RIVM) in The Netherlands (Dick van Soolingen’s lab) and in the Mycobacterial Unit of the Institute of Tropical Medicine in Antwerp.
best wishes
Ruth

I appreciate all the great responses. Currently, we will not be treating MOTT even if on 2 samples or more. We cannot speciate because of lack of resources, so no point in treating. If anything changes, will post here. And please feel free to add more comments. I find this site very helpful.