Improvement in Plasma Drug Activity during the Early Treatment Interval among Tanzanian Patients with Multidrug-Resistant Tuberculosis |
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| Authors: | Norah D Ndusilo Scott K Heysell Stellah G Mpagama Jean Gratz Farida H Segesela Saumu J Pazia Xin-Qun Wang Eric R Houpt Gibson S Kibiki |
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| Institution: | 1. Kilimanjaro Clinical Research Institute, Moshi, Tanzania.; 2. Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, United States of America.; 3. Kibong’oto Infectious Diseases Hospital, Sanya Juu, Tanzania.; 4. Department of Public Health Sciences, University of Virginia, Charlottesville, United States of America.; Hospital San Agustín. Aviles. Asturias. Spain, SPAIN, |
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| Abstract: | BackgroundIndividual pharmacokinetic variability may be common in patients treated for multidrug-resistant tuberculosis (MDR-TB) but data are sparse from resource-limited settings and across the early treatment interval.MethodsPlasma drug activity, as measured by the TB Drug Activity (TDA) assay at 2 and 4 weeks of treatment with a standardized MDR-TB regimen was performed in patients with pulmonary MDR-TB from Tanzania. TDA values were correlated with measures of early treatment outcome including every two week collection of sputum for time-to-positivity (TTP) in liquid culture from the MGIT 960 automated system. Patients were evaluated at 24 weeks and those surviving without delayed sputum culture conversion (>8 weeks), culture reversion after previously negative, or weight loss were defined as having a favorable outcome.ResultsTwenty-five patients were enrolled with a mean age of 37 ±12 years. All were culture positive from the pretreatment sputum sample with a mean TTP in MGIT of 257 ±134 hours, and the median time to culture conversion on treatment was 6 weeks. Twenty patients (80%) had an increase in TDA, with the overall mean TDA at 2 weeks of 2.1 ±0.7 compared to 2.4 ±0.8 at 4 weeks (p = 0.005). At 2 weeks 13 subjects (52%) had a TDA value > 2-log killing against their own M. tuberculosis isolate compared to 17 subjects (68%) at 4 weeks (McNemar’s exact test p = 0.29). An interim treatment outcome was able to be determined in 23 patients (92%), of whom 7 had a poor outcome (30%). An increase in TDA from week 2 to week 4 was associated with favorable outcome, unadjusted OR = 20.0, 95% CI: 1.61–247.98, exact p = 0.017 and adjusted OR = 19.33, 95% CI: 1.55–241.5, exact p = 0.023].ConclusionsThe majority of patients with MDR-TB in Tanzania had an increase in plasma drug activity from week 2 to week 4 of treatment as measured by the TDA assay. Understanding the etiology and full impact of this dynamic may inform therapeutic intervention. |
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