Characteristics of Pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis and its correlation with second-line drug resistance

ObjectiveTo investigate the characteristics of the resistance to Pyrazinamide in multidrug-resistant (MDR) Mycobacterium tuberculosis（MTB） strains and its correlation with the second-line drug resistance in Ningbo.

MethodsA total of 110 MDR-TB isolates selected in the drug resistance survey in Ningbo between 2015 and 2017 were used in the study. The conventional drug susceptibility test (1% ratio method) was used to detect the drug-resistant profiles of MDR-MTB against 5 second-line antibiotics (ofloxacin, levofloxacin, kanamycin, amikacin, capreomycin). BACTEC MGIT 960 PZA method was used to detect Pyrazinamide resistance of 110 MDR-MTB isolates and gene sequencing was conducted to detect the mutation of pncA gene.

ResultsAmong the 110 isolates of MDR-MTB, 65 were resistant to Pyrazinamide (59.09%). pncA gene mutation occurred in 56 strains of MDR-MTB (50.91%). Among the 65 Pyrazinamide resistant strains, pncA mutation was detected in 54 strains (83.08%). Among the 45 Pyrazinamide sensitive strains, pncA mutation was detected in 2 strains (4.44%). The mutation rate of pncA was much higher in Pyrazinamide resistant strains than in Pyrazinamide sensitive strains, the difference was significant (χ²＝65.787, P＜0.001). There were 42 mutation types in pncA gene, and single base substitution was the main type (92.86%). The resistance to streptomycin, ethambutol, ofloxacin, levofloxacin and pre-extensive drug resistance (pre-XDR) were associated with Pyrazinamide resistance in MDR-MTB strains.

ConclusionMDR-MTB clinical isolates were resistant to Pyrazinamide seriously, and the Pyrazinamide resistance was associated with the resistances to second line antibiotics (ofloxacin, levofloxacin) and pre-XDR.