Phenotypic susceptibility testing of pyrazinamide in lineage 1 M.tuberculosis isolates – a North London cohort experience

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Background: Mechanisms for pyrazinamide (Z) resistance in Mycobacterium tuberculosis (M.tb) remain poorly understood. Recently it has been suggested that Z monoresistance is commoner amongst lineage 1 Indo-Oceanic isolates. As this Z resistance is not mediated through recognised pncA mutations, formal phenotypic testing is required for detection (Modlin, S.J. et al. Antimicrobial Agents and Chemotherapy 2021;65). We sought to identify how this applied to a North-London cohort. Aims: To identify: 1. The proportion of lineage 1 isolates 2. The rate of phenotypic Z resistance 3. The time from specimen microscopy to confirmation of Z status. 4. Whether phenotypic Z resistance altered treatment management. Methods: A review of M.tb isolates in patients at a TB centre between 01/01/22 and 31/01/23. Results: Twelve patient isolates were identified as having lineage 1 M.tb strains, of which four (33.3%) were phenotypically Z resistant. The median number of days from sample microscopy to availability of phenotypic susceptibility was 91 days. In 2 patients, treatment for Z was stopped after lineage 1 phenotypics were confirmed. In 5 patients, Z was stopped for other reasons. In 4 patients, Z treatment had already been completed. One patient is still receiving Z despite their lineage 1 status. One patient stopped isoniazid due to peripheral neuropathy and was later found to have phenotypic Z resistance. Conclusions: Currently, it is not clear if lineage 1 phenotypic low level Z resistance affects risk of relapse. Increased awareness of these findings may influence management, especially if there are challenges with remaining antituberculous regimen.

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