Drug Susceptibility Testing for Optimizing Tuberculosis Treatment

Sami      O. Simons; Dick      van Soolingen

doi:10.2174/138161211797470255

Abstract

The principles of our current drug susceptibility testing (DST) for tuberculosis (TB) have already been laid out in 1963. Since then, DST has not gained much popularity owing to the long turn-around time and the introduction of potent antituberculosis drug regimens. These and other barriers have led to a critical gap in laboratory capacity in DST of Mycobacterium tuberculosis. However, owing to the emergence of multidrug resistant tuberculosis there is a pressing need for adequate and rapid DST.

In recent years, methods for fastening the diagnosis of drug resistant tuberculosis have been developed. Semi-automated (non)- radiometric liquid culture systems reduced the turn-around-time significantly. With the introduction of molecular diagnostic methods, such as reverse line probes and the recently introduced semi-automated real-time PCR, the turn-around time of at least an indicative resistance testing has dropped from days to hours. However, much more can be gained in the development of fast phenotypic and molecular DST methodologies. Recently also pharmacodynamic studies have also added significantly to our understanding of resistance development in tuberculosis treatment.

This article provides an overview of the most important DST techniques now available, with their characteristics, biosafety aspects, reproducibility and required quality control. Also the findings in pharmacodynamic studies and required future research are discussed. We will argue that drug susceptibility testing in TB treatment is an essential tool for adequate TB control and prevention of resistance and should be applied to all patients to guide TB treatment. Perhaps in the near future even individualized treatment doses could be an important help to prevent further emergence or further development of resistance.

Keywords: Tuberculosis, review, microbial sensitivity tests, multidrug resistant tuberculosis, antitubercular agents, pyrazinamide, pncA gene, moxifloxacine, streptomycin, point mutations