Mutations responsible for Mycobacterium tuberculosis isoniazid resistance in Italy

SETTING: The incidence of tuberculosis (TB) and drug resistance in Italy is low compared to other countries. Mutations in several genomic regions of Mycobacterium tuberculosis are involved in the occurrence of isoniazid (INH) resistance. OBJECTIVE: To investigate the mutations responsible for INH resistance among Italian isolates of M. tuberculosis, to assess the feasibility of predicting drug resistance using a genetic approach. DESIGN: The mutations responsible for INH resistance were looked for in selected regions of genes katG, kasA and ndh and in the promoter regions of inhA and ahpC by nucleotide sequencing, and the results were compared with data reported in other studies. RESULTS: Prevalent INH resistance mutations were found at codon 315 of the katG gene and at position -15 of the inhA regulatory region (respectively 37.8% and 20.0% of isolates). The prevalence of mutations at position -24 of inhA, in ahpC, and in kasA ranged from 2.2% to 4.4%. No mutations were found in 35.6% of the isolates. CONCLUSION: The identification of INH resistance by genetic analysis of the selected regions may be inappropriate in areas with a low prevalence of TB, such as Italy, as the genetic mechanisms of resistance remain unidentified for approximately one third of the isolates.