Please tell us a little bit about the BTS MDRTB Clinical Advice Service?
The BTS MDR-TB Clinical Advice Service provides advice and support to clinicians across the UK who care for patients with Multi-drug resistant TB(MDR-TB). The advice is offered by a multidisciplinary panel of Clinical Service Advisers, with expertise in respiratory medicine, infectious diseases, microbiology, pharmacy and public health. The advice is provided via a secure online case discussion forum and at monthly MDT meetings which are held via Teams.
Expert clinical advice on the treatment and monitoring of cases of MDR-TB has a direct and immediate impact on patient care. These cases are increasingly complex, and access to prompt, expert advice is a highly valued resource. In addition the service ratifies the use of the high cost treatments and is a requirement of commissioning for these in England.
The National Mycobacterial Reference Service (NMRS) recently issued a note highlighting that there is an ongoing international issue with the media testing for phenotypic susceptibility to pyrazinamide (PZA) and that, therefore, pyrazinamide drug susceptibility testing may be unreliable.
Why is this important?
TB clinicians rely on phenotypic sensitivity testing in cases of drug resistance or where whole genome sequencing cannot reliably confirm sensitivity to first line TB drugs. The current issue only relates to PZA sensitivity testing media but this is of great importance as PZA is a key drug for TB and allows us to ensure a 6 month standard TB regime for drug sensitive TB is sufficient.
This therefore affects TB isolates where phenotypic PZA sensitivity would normally be tested. These are:
- Isolates with an unknown PZA mutation
- Multidrug resistant TB (where full phenotypic susceptibility panels are always performed)
- Lineage 1 TB (where the existing genetic mutation catalogues for PZA do not adequately explain phenotypic resistance and where 20% of isolates are resistant). Isolates that were lineage 1 were previously checked using phenotypic drug susceptibility testing and coded as “resistant” if resistant by phenotype even if sensitive by WGS . This current issue therefore raises doubt over that confirmatory phenotypic PZA susceptibility prediction.
What steps can clinicians take?
In cases that have MDR MTB, mixed resistance MTB or have an unknown PZA mutation; clinicians should consider the potential additional PZA resistance (which may require modifying the patient’s drug regimen) and seek advice from BTS MDR-TB Clinical Advice Service.
If the sample is lineage 1 MTB (10-15% of all cultured MTB), we suggest that for the time being all isolates of lineage 1 should be regarded as a potentially PZA-resistant organism. In the setting where the lineage 1 organism is either fully sensitive by WGS or PZA monoresistant by WGS but with phenotypic PZA resistance, to consider where possible a PZA-resistant regimen of 2RHE(Z) then 7RH. However it is worth noting that if the organism is both WGS and phenotypically susceptible, it is likely that PZA is still an active agent. If the case is an MDR or mixed resistance lineage 1 MTB, then we suggest that clinicians seek advice from the MDR TB CAS (MDR-TB Clinical Advice Service (brit-thoracic.org.uk)) and in the meantime take account the potential additional PZA resistance (which may require modifying the patient’s drug regimen)
Does this apply across the UK?
This testing issue is international and therefore applies to all TB services across the UK relying on pyrazinamide drug susceptibility testing.
How can clinicians seek advice from the MDR-TB CAS?
Clinicians should register with the CAS (here) and then, after completing case related demographic and clinical information, they will be able to post their query to the Service.
Non-case specific advice can be sought by emailing MDRTB@brit-thoracic.org.uk.
For any microbiological/ WGS queries around your case please contact: uhb-tr.nmrs@nhs.net
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