Concomitant increases in spectrum and level of drug resistance in Mycobacterium tuberculosis isolates

To determine the drug resistance spectrum and resistance levels of extensively drug-resistant (XDR-) and multidrug-resistant tuberculosis (MDR-TB) and TB resistant to either rifampicin (RMP, R) or isoniazid (INH, H; R/H-DR).

Of 142 drug-resistant clinical isolates examined, 13 were XDR-TB, 66 were MDR-TB and 63 were R/H-DR. The drug resistance spectrum was tested by the absolute two-concentration method. Minimum inhibitory concentrations (MICs) were determined for the strains by agar dilution method on Löwenstein-Jensen slants.

The drug resistance spectrum of XDR-TB, MDR-TB and R/H-DR TB isolates ranged from 4 to 9, 2 to 6 and 1 to 5 drugs, respectively. Over half of all XDR-TB (53.8%), MDR-TB (66.7%) and R/H-DR (54.0%) isolates were resistant to two other anti-tuberculosis drugs; 38.5% of XDR-TB, 24.2% of MDR-TB and 28.6% of R/H-DR TB isolates were resistant to ≥ 3 additional anti-tuberculosis drugs in addition to those originally defined, demonstrating that the MIC values and the proportions of strains with higher MICs followed a trend of XDR-TB > MDR-TB > R/H-DR for INH, RMP, ofloxacin and ethambutol.

XDR-TB, MDR-TB and R/H-DR TB isolates exhibited both increasingly broader resistance spectra and a higher percentage of strains with high MICs to more frequently resistant drugs, which might be related to patterns of TB chemotherapy.