Lopez, J. M., Zimic, M., Vallejos, K., Sevilla, D., Quispe-Carbajal, M., Roncal, E., Rodríguez, J., Rodríguez, J., Antiparra, R., Arteaga, H., Gilman, R., Maruenda, H., Sheen, P. JCM (accepted).
Pyrazinamide (PZA), an antituberculosis pro-drug, is recommended by WHO for first and second line tuberculosis (TB) treatments. Its importance relies, among other, on the specific activity it has against M. tuberculosis (Mtb) persister cells and that its use helps reduce the duration of the treatment and prevents relapse. However, it has been demonstrated that its use in patients infected with PZA resistant Mtb strains is associated with higher mortality rates..As of today, there are no accurate PZA-susceptibility tests applicable to routine clinical analysis to be used as an aid to timely establish the most appropriate drug-regime for a TB-patient.
The paper describes a new method – precise and quantitative- based in Nuclear Magnetic Resonance spectroscopy to address PZA drug resistance in patients infected with Mtb. The method was developed for clinical sputum samples and quantifies the hydrolysis of PZA into is active form pyrazinoic acid, POA, through the direct detection of the NMR resonances of these two compounds.
The comparison of the accurate % POA quantitative NMR data against other drug susceptibility tests (DST), such as Mycobacterial Growth Indicator Tube (indirect), classic Wayne test (direct but visual colorimetric assessment of POA), Sequencing pncA gene mutations (mutation that reduces PZase activity), and a more recent qualitative colorimetric method also developed by us, MODS-WAYNE (POA detection with WAYNE staining in the supernatant of the sputum culture), has permitted to determine a direct correlation between the amount of POA in the sputum samples culture and PZA drug susceptibility of the Mtb strains. In this paper, thresholds are proposed to more accurately diagnose, in less time that other DSTs, if the TB patient is carrying a susceptible or persistent Mtb strain.
Autor(es):Juan Lopez, Mirko Zimic, Katherine Vallejos, Diego Sevilla, Mariella Quispe-Carbajal, Elisa Roncal, Joseline Rodríguez, Jhojailith Rodríguez, Ricardo Antiparra, Héctor Arteaga, Robert Gilman, Helena Maruenda, Patricia Sheen
Año: 2023
Título de la revista: JCM