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.