Session: Poster Session: Resistance in Mycobacteria
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: Tuberculosis continues to be a significant health care problem, not only in the developing countries. Worldwide, the present trend is characterized by an alarming emergence in drug resistance, raising concerns of future epidemics of virtually untreatable TB. Given the limited therapeutic options in MDR (and especially XDR) tuberculosis, it is essential to know resistance levels and mechanisms present in clinical isolates categorized as drug resistant on the basis of critical concentration testing, so as to facilitate rapid therapeutic decisions. Methods: We determined quantitative resistance levels of drug resistant clinical isolates of Mycobacterium tuberculosis sampled in Switzerland over the past 3 years with the view to determine if therapeutic options with first-line drugs still exist in these isolates. Results: Rifampicin resistant isolates unanimously showed a high-level resistant phenotype (> 50 μg/ml) associated with mutations in rpoB. In contrast, a significant fraction of clinical TB isolates categorized as isoniazid resistant in the diagnostic laboratory showed only a low-level resistant phenotype (mostly mutations in inhA) and heterogeneous phenotypic resistance levels were associated with mutations in katG. Ethambutol resistance occurred mostly in MDR strains and was linked to alterations in embB, but resistance never exceeded 25 μg/ml. Conclusion: Our data indicate that some first line agents may be considered as therapeutic treatment option despite in vitro resistance at the critical concentration. Diagnostic mycobacteriology would benefit from standardized measures of quantitative drug susceptibility testing in particular for those drugs where significant variations in phenotypic resistance levels are found in clinical isolates, e.g. isoniazid, ethambutol and streptomycin.