PURPOSE: Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. MATERIALS AND METHODS: The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (microg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). CONCLUSION: The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.
Adult ; Aged ; Antitubercular Agents/blood/*pharmacokinetics/therapeutic use ; Chromatography, High Pressure Liquid ; Cycloserine/blood/*pharmacokinetics/therapeutic use ; Fluoroquinolones/blood/*pharmacokinetics/therapeutic use ; Humans ; Medication Adherence ; Middle Aged ; Prothionamide/blood/*pharmacokinetics/therapeutic use ; Retrospective Studies ; Sputum/*microbiology ; Tandem Mass Spectrometry ; Tuberculosis, Multidrug-Resistant/blood/*drug therapy ; Young Adult

OBJECTIVETo study the distribution of isoniazid and its metabolite in spinal tuberculosis following chemotherapy.

METHODSTwenty-three patients with spinal tuberculosis received chemotherapy with 2SHRZ/16HRZ (for a total of 18 months). Four weeks after the chemotherapy, all the patients underwent surgery and specimens of the serum, ilium and vertebral tissue including the sclerotic wall, focus inside the sclerotic wall (if present) and destructed foci were obtained. CT was performed in all the cases to test the HU of the foci before operation, and the levels of isoniazid and its metabolite in the specimen were measured with high-performance liquid chromatography (HPLC).

RESULTSThe levels of isoniazid and its metabolite were the highest in the serum, followed by normal ilium and non-sclerotic bone, and were extremely low in the sclerotic wall and foci. Their levels in the non-sclerotic bone of the compromised vertebra and normal vertebra showed no significant difference (P>0.05), but in the sclerotic bone, their levels were significantly higher than in the normal vertebra (P<0.05). Isoniazid and its metabolite are hardly detectable in the sclerotic foci in the compromised vertebrae.

CONCLUSIONIsoniazid and its metabolite may reach therapeutic concentration in normal vertebra and nonsclerotic bones of the compromised vertebra, but not in the disease foci or the sclerotic bone of the compromised vertebrae.

Adult ; Aged ; Antitubercular Agents ; blood ; pharmacokinetics ; therapeutic use ; Chromatography, High Pressure Liquid ; Female ; Humans ; Isoniazid ; analogs & derivatives ; blood ; pharmacokinetics ; therapeutic use ; Lumbar Vertebrae ; metabolism ; Male ; Middle Aged ; Tuberculosis, Spinal ; drug therapy ; Young Adult