Neuroleptic drugs in the treatment of tuberculosis: Minimal inhibitory concentrations of different phenothiazines against Mycobacterium tuberculosis.

Due to an increase of drug resistant TB, alternative drugs that are not currently listed in the WHO guidelines on MDR TB treatment are currently being evaluated. Our group tested 100 susceptible, 20 MDR and 2 XDR Mtb strains against the phenothiazine derivatives thioridazine, trifluoperazine and triflupromazine. MIC testing was performed on Middlebrook 7H10 agar and was defined as the lowest drug concentration that inhibits ≥99% of the bacterial population. We confirm very good in vitro activity of phenothiazines against Mycobacterium tuberculosis. In >77% of all strains MICs of ≤10 µg/ml were found.

Minimal inhibitory concentrations of first-line drugs of multidrug-resistant tuberculosis isolates.

CONTEXT: The treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is consistently difficult. Besides resistances, drug availability can be problematic and costs for therapy are high. AIMS: Our aim was to evaluate alternatives in treatment of MDR and XDR TB other than using second-line drugs. MATERIALS AND METHODS: We analyzed retrospectively the minimal inhibitory concentrations (MICs) of first-line drugs for 44 multidrug-resistant Mycobacterium tuberculosis isolates determined in our institute over a period of 20 years (1990 - 2010, n = 44). Drug susceptibility testing (DST) was performed using the proportion method on Lowenstein-Jensen Medium or Middlebrook 7H10 agar. MICs were defined as the lowest drug concentration after two-fold serially diluted concentration of the drugs that inhibits growth of more than 99.0% of a bacterial proportion of the tested M. tuberculosis within 14 to 21 days of incubation at 37°C. STATISTICAL ANALYSIS USED: Summation. RESULTS: The MICs of isoniazid and ethambutol were equal or slightly above the critical concentration in most of the strains (92% and 84%, respectively), defined as "low-level resistance". Rifampicin and streptomycin exhibited very high MICs in most of the strains (100% and 77%, respectively), indicating a "high-level resistance". CONCLUSION: Our results indicate that isoniazid and ethambutol could still play a role in treating MDR and XDR TB patients if low-level resistance is detected. Quantitative DST seems to be promising for the recognition of residual drug activity, but has to be confirmed by clinical studies.