Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern. O B J E C T IVE : To determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP). DESIGN: Isolates from two major urban centres-Paris (101 strains) and Shanghai (171 strains)-were investigated for the association of pncA mutations with resistance to drugs other than PZA. RESULTS : The proportion of pncA mutations found in INH-monoresistant strains was not increased. CONCLUSION: pncA mutations associated with PZA resistance were found almost exclusively in MDR-TB strains, underlining the importance of determining PZA resistance when treating MDR- or XDR-TB.