Antimicrobial Resistance related Selection of appropriate treatment and infection control measures by integrated high throughput genotyping and drug resistance determination of M. tuberculosis clinical isolates
09 / 2010 - 11 / 2013
The overall goal of the proposed project is to improve control and treatment of drug-resistant TB by providing tools that allow rapid testing for TB drug resistance Background With approximately 1000 newly diagnosed tuberculosis (TB) cases per year, the Netherlands is among the countries with the lowest prevalence and incidence of tuberculosis (TB). Although this number is historically low, globalization, expansion of the EU, and the emergence of drug resistant and virulent strains are threatening a resurgence of tuberculosis (TB) in Europe. The former Soviet states in particular are a reservoir for drug resistant forms of TB. Therefore, methods should be in place that enable rapid diagnosis of TB and detection of drug resistance. This would be most effectively achieved by improved case finding in both the high and low burden countries, but current mycobacterial characterization methods are complex and difficult to implement. The prevalence and spread of MDR/XDR-TB, and therefore the urgency to timely switch from first to second line therapy, will increase in the coming years. Moreover, with the expected introduction of new drugs for treatment of complicated TB cases, an efficient screening method for resistance to all agents will be needed. We aim to develop, implement and evaluate a standardized high throughput screening assay, based on the simultaneous detection of single nucleotide polymorphisms (SNPs)/genetic rearrangements. This assay will combine species identification, genotyping and detection of first- and second-line drug resistance with readout on a robust platform. Combining these functions on a dedicated system will make the assay suitable for widespread implementation and thereby facilitate rapid selection of the most efficacious treatment and control measures.