ORCID Profile
0000-0002-5956-8384
Current Organisation
Imperial College London
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Publisher: Elsevier BV
Date: 10-2020
Publisher: American Society for Microbiology
Date: 19-01-2022
DOI: 10.1128/JCM.01907-21
Abstract: Pyrazinamide is an important component of both drug-susceptible and drug-resistant tuberculosis treatment regimens. Although approximately 50% of rif in-resistant isolates are also resistant to pyrazinamide, pyrazinamide susceptibility testing is not routinely performed due to the challenging nature of the assay.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Oxford University Press (OUP)
Date: 04-02-2020
DOI: 10.1093/JAC/DKZ564
Abstract: Molecular assays are endorsed for detection and confirmation of rif icin-resistant TB. The frequency, causal mechanisms and impact of discordant results between molecular tests are not well understood. The prevalence of discordant results was determined by pairwise comparison of molecular test results in a cohort of 749 rif icin-resistant TB patients in three South African provinces. Culture isolates were sent to a research laboratory for WGS and rif icin MIC determination. Clinical information was collected through medical file review. The prevalence of discordances between Xpert MTB/RIF and MTBDRplus was 14.5% (95% CI 10.9%–18.9%), 5.6% (95% CI 2.2%–13.4%) between two consecutive Xpert assays and 4.2% (95% CI 2.2%–7.8%) between two consecutive MTBDRplus assays. Likely mechanisms of discordances were false rif icin susceptibility on MTBDRplus (due to variants not included in mutant probes or heteroresistance with loss of minor variants in culture), false resistance on molecular assay in rif icin-susceptible isolates, and human error. The healthcare worker changed the treatment regimen in 33% of patients with discordant results and requested 232 additional molecular tests after a first confirmatory test was performed in 460 patients. A follow-up Xpert assay would give the healthcare worker the ‘true’ rif icin-resistant TB diagnosis in at least 73% of discordant cases. The high rate of discordant results between Xpert and MTBDRplus has important implications for the laboratory, clinician and patient. While root causes for discordant result are multiple, a follow-up Xpert assay could guide healthcare workers to the correct treatment in most patients.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: South Africa
No related grants have been discovered for Michael Whitfield.