Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance

International audienceBackground: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern. The objective was to determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP). For this goal, 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.The proportion of pncA mutations found in INH-monoresistant strains was not increased. In sum, 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