Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize
drug management. Patients with
drug-resistant
pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure
pyrazinamide concentrations. Among 10 patients, the median
pyrazinamide dose was 24.7 mg/kg of
body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had
necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum
pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free
pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum
pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue
pyrazinamide concentrations and the amounts of
necrosis (R = -0.66, P = 0.04) and
acid-fast bacilli (R = -0.75, P = 0.01) identified by histopathology. We found good penetration of
pyrazinamide into lung tissue among patients with
pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to
pyrazinamide activity. The tissue penetration of
pyrazinamide highlights its importance in both
drug-susceptible and
drug-resistant antituberculosis treatment regimens.