Collaborators:
Name |
Country |
Institution
|
Keertan Dheda |
South Africa |
UCT Lung Institute |
Taane Clark |
United Kingdom |
LSHTM |
Objectives:
Aim 1: To investigate pharmacokinetic (PK) mismatch within TB cavities obtained from resected lungs of incurable TB patients undergoing surgery (n=30) by determining the concentrations of the WHO group A, B and C drugs (bedaquiline, delaminid, linezolid, clofazimine) at distinct biopsy points across these cavities and their relationship to genotypic and phenotypic MIC’s at the same points and in serial sputum samples
Aim 2: To evaluate targeted deep sequencing for the detection of micro-heteroresistant populations in the sputum relative the site of disease (epithelial lining fluid, lung biopsies from cavity tissue; See Figure 2) in incurable TB patients undergoing lung resection (n=20).
Study Design:
Prospective cohort
Outcomes:
Aim 1 primary outcome measure: TB drug specific concentrations at anatomically distinct points in TB cavities and other lesions correlated to MICs at these equivalent points.
Aim 2 primary outcome measure: correlation of genotypic resistance mutations identified in the sputum to those in the lung
Other outcome measures: detection and quantification of TB drug in the exhaled breath of drug resistant TB patients compared to serum and lung tissue (Aim 1.3)
Linked Grant:
EDCTP Clinical Research & Development Fellowship