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Improvement in plasma drug activity during the early treatment interval among Tanzanian patients with multidrug-resistant tuberculosis.

Ndusilo ND, Heysell SK, Mpagama SG, Gratz J, Segesela FH, Pazia SJ, Wang XQ, Houpt ER, Kibiki GS - PLoS ONE (2015)

Bottom Line: 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 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].

View Article: PubMed Central - PubMed

Affiliation: Kilimanjaro Clinical Research Institute, Moshi, Tanzania.

ABSTRACT

Background: Individual 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.

Methods: Plasma 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.

Results: Twenty-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].

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus

Sputum culture positive by week in MGIT system, N = 25.All patients (100%) culture positive from pretreatment sputum specimen.
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pone.0122769.g001: Sputum culture positive by week in MGIT system, N = 25.All patients (100%) culture positive from pretreatment sputum specimen.

Mentions: All patients were culture positive from the pretreatment sputum sample with a mean TTP in MGIT of 257 ±134 hours (minimum 123 hours; maximum 588 hours). Eleven patients (44%) had a TTP of less than 216 hours (9 days). The median time to culture conversion was 6 weeks (minimum 2 weeks; maximum 12 weeks). Twenty-one patients (84%) were culture negative at 8 weeks (Fig. 1). Two patients that were culture negative at 2 weeks, were again culture positive at 10 weeks (though of low bacterial burden, TTP in MGIT of 725 and 935 hours at 10 weeks), but ultimately culture negative again at 12 weeks and upon subsequent monthly evaluations per hospital protocol. Thus, these patients were classified as culture converted at 12 weeks.


Improvement in plasma drug activity during the early treatment interval among Tanzanian patients with multidrug-resistant tuberculosis.

Ndusilo ND, Heysell SK, Mpagama SG, Gratz J, Segesela FH, Pazia SJ, Wang XQ, Houpt ER, Kibiki GS - PLoS ONE (2015)

Sputum culture positive by week in MGIT system, N = 25.All patients (100%) culture positive from pretreatment sputum specimen.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376785&req=5

pone.0122769.g001: Sputum culture positive by week in MGIT system, N = 25.All patients (100%) culture positive from pretreatment sputum specimen.
Mentions: All patients were culture positive from the pretreatment sputum sample with a mean TTP in MGIT of 257 ±134 hours (minimum 123 hours; maximum 588 hours). Eleven patients (44%) had a TTP of less than 216 hours (9 days). The median time to culture conversion was 6 weeks (minimum 2 weeks; maximum 12 weeks). Twenty-one patients (84%) were culture negative at 8 weeks (Fig. 1). Two patients that were culture negative at 2 weeks, were again culture positive at 10 weeks (though of low bacterial burden, TTP in MGIT of 725 and 935 hours at 10 weeks), but ultimately culture negative again at 12 weeks and upon subsequent monthly evaluations per hospital protocol. Thus, these patients were classified as culture converted at 12 weeks.

Bottom Line: 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 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].

View Article: PubMed Central - PubMed

Affiliation: Kilimanjaro Clinical Research Institute, Moshi, Tanzania.

ABSTRACT

Background: Individual 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.

Methods: Plasma 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.

Results: Twenty-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].

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus