Molecular techniques in the diagnosis of drug-resistant tuberculosis

In the last few years, there has been considerable progress in our understanding of the mechanisms of action and resistance to anti-tuberculosis agents. To date, there is information about 11 genes involved in resistance to all major anti-tuberculous drugs in Mycobacterium tuberculosis. Mutations in katG, inhA and ahpC genes are found in up to 90% of isoniazid-resistant strains, rifampin resistance is associated (> 96%) with rpoB mutations, pyrazinamide resistance with pncA mutations (72% to 97%), ethambutol resistance with mutations in embB (47% to 65%), streptomycin resistance with rrs or rpsL mutations (70%), and fluoroquinolone resistance with gyrA substitutions (75% to 94%). Additional genes and mechanisms may play a role, particularly in association with lower levels of resistance. Based on this growing set of information, genotypic analysis of resistance is becoming a real possibility, and novel tests are being developed. Issues such as effectiveness, cost-efficiency, and appropriate setting for the implementation of these techniques are not yet established.