Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB

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.

Adrenocortical reserve and morphology in tuberculosis.

Ninety seven patients (63 males, mean age 31.8 years, SD 2.3) with various forms of tuberculosis were studied. All of them were HIV negative. Thirty normal control subjects (16 males, mean age 36.4 years, SD 1.8) were also studied. Fifty-eight of the 97 patients (59.8%) were malnourished (BMI < 18 kg/m2). The mean basal serum cortisol was lower in the TB group (n = 91) (351 nmol/1; SD 150) as compared to the normal control group (n = 8) (402 nmol/1; SD 93) but this difference did not attain statistical significance. Following administration of synthetic ACTH (cosyntropin), the 30 and 60 minutes mean serum cortisol values in the TB group were significantly lower as compared to the normal control group (p < 0.05). Forty five of the 91 patients (49.5%) who underwent the ACTH stimulation test had compromised adrenal reserve. Fourteen of the 86 patients (16.3%) in whom adrenal morphology was studied revealed adrenal gland enlargement on abdominal CT scan. ACTH stimulation was done in 12 of these 14 patients and eight of them had compromised adrenal reserve. Repeat ACTH stimulation done six months to one year after treatment in 13 patients revealed significantly increased 30 minutes (p < 0.05) and 60 minutes (p < 0.05) serum cortisol values. While nine of these 13 patients were negative responders before treatment, only three of them had evidence of compromised adrenal reserve after one year of antituberculosis treatment, (p < 0.05). Serum cortisol values in patients with drug-sensitive and drug-resistant tuberculosis did not differ significantly. Patients with drug-resistant tuberculosis had a higher prevalence of adrenal gland enlargement (7 of the 30) as compared to those with drug-sensitive tuberculosis (7 of the 56) (p = NS). Subclinical adrenal insufficiency is prevalent in a significant number of patients with both drug-sensitive and drug-resistant tuberculosis, and in some of these it is associated with adrenal gland enlargement. The compromised adrenal reserve and enlargement seem to reverse with therapy.

Serum angiotensin converting enzyme activity in sarcoidosis and pulmonary tuberculosis.

Serum angiotensin converting enzyme (SACE) was estimated in 18 cases of sarcoidosis, 15 patients suffering from pulmonary tuberculosis and in 12 normal healthy individuals. SACE was elevated in the patients suffering from sarcoidosis. (33.2 +/- 12.9). SACE values for the pulmonary tuberculosis patients were 18.8 +/- 7.9 and those for the normal healthy individuals were 17.1 +/- 4.7. Compared to pulmonary tuberculosis and normal healthy individuals, the SACE levels were significantly elevated (P < 0.01) in sarcoidosis patients.