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Evolution of drug resistance and treatment outcome within a longitudinal retrospective study – linking outcome to treatment.

M Grobbelaar(1) R M Warren(1) H Cox(2) A Dippenaar(3)

1:Stellenbosch University; 2:University of Cape Town; 3:University of Antwerp

We investigated 47 DR-TB cases with multiple isolates in a large retrospective cohort study in a high TB-incidence setting in Cape Town, South Africa. DNA was extracted using the CTAB extraction method. WGS was performed using the Illumina platform. Sequences were analyzed with a customized pipeline using open-source software. Drug resistance-conferring and associated mutations were identified using TB-Profiler.  

The cohort consisted of 18 female and 29 male patients. WGS data were used to divide the cohort into groups, 29 patients had changes in their drug-resistance (DR) profiles while 18 patients had the same DR profile irrespective of episodes. Of the 18 patients (same DR), 16% had no previous TB while 83% had previous TB. In the group with DR changes, 13% had no previous TB, while 86% had previous TB, indicating that previous TB did not influence the evolution of DR within the new episodes. When treatment was linked to the outcome, 64% of episodes were cured when patients received ≥ 4 drugs however 31% of patients were still cured even with < 3 effective drugs. More patients also failed treatment when they received < 3 effective drugs (50%), however, 21% of patients still failed regardless of receiving ≥ 4 drugs. Of patients with an LTFU outcome, 52% received 3 drugs, while only 33% of patients received ≥ 4 effective drugs. Finally, more patients died when they received ≥ 4 drugs compared to 7% and 29% that received 3 or ≤ 3 effective drugs respectively.   

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