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

Abstract

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.