Drug-susceptibility testing in tuberculosis: methods and reliability of results

TLDR: In vitro criteria of resistance for susceptibility testing should be carefully determined with representative clinical samples of Mycobacterium tuberculosis isolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results.

Abstract: The demand for reliable drug-susceptibility testing (DST) increases with the expansion of antituberculosis drug-resistance surveillance, and with the need for an appropriate treatment of multidrug-resistant tuberculosis, whose incidence gradually increases in many parts of the world. However, the reliability of DST results obtained through widely used methods does not meet acceptable levels, except for DST to isoniazid and rifampicin. In general, susceptibility results are highly predictable, while resistance results show low predictive values when the resistance prevalence is <10%. Poor reliability stems from a weak correlation with clinical response and a low reproducibility due to the poor standardisation of the complex and fragile test procedures. Therefore, in vitro criteria of resistance for susceptibility testing should be carefully determined with representative clinical samples of Mycobacterium tuberculosis isolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results. The critical concentration of some drugs is close to the minimal inhibitory concentration for wild susceptible strains and, thus, drug-susceptibility testing is prone to yield poorly reproducible results. These issues call for physicians' attention when using the results from drug-susceptibility testing for case management.