Genetic surveillance and outcomes of pyrazinamide and fluoroquinolones-resistant tuberculosis in Taiwan

Abstract

Background: Pyrazinamide (PZA) and fluoroquinolone (FQ), particularly moxifloxacin (MXF), are essential drugs in the World Health Organization (WHO) recommended short-course regimen to treat drug-susceptible tuberculosis (TB). Methods: To understand the extent of PZA and MXF susceptibility in general TB cases in Taiwan, we conducted retrospective analyses of 385 conservative Mycobacterium tuberculosis complex (MTBC) isolates identified from 4 TB laboratories in different regions of Taiwan. The case information was obtained from the TB registry. Genotypic drug susceptibility testing (DST) was performed by sequencing drug-resistance associated genes, PZA (pncA) and FQ (gyrA, and gyrB). Phenotypic DST was determined using the Bactec MGIT 960 system or the agar proportion method. Genotyping was carried out using spacer oligonucleotide typing. Results: In this study, 4.7% (18/385) cases' isolates harbored pncA mutations and 7.0% (27/385) cases’ isolates harbored gyrA or gyrB mutation. Notably, pncA mutation was associated with Beijing family genotypes (P = 0.028), East African-Indian (EAI) genotypes (P = 0.047) and MDR-TB (P < 0.001). Whereas, gyrA or gyrB mutation was associated with EAI genotypes (P = 0.020) and MDR-TB (P = 0.006). In addition, a statistically significant difference was found between the favorable outcomes using active and inactive PZA (P = 0.009) in 38 case isolates with any pncA, gyrA, or gyrB mutation. Conclusion: We concluded that routine PZA and FQ susceptibility tests are recommended for guiding the treatment of TB.

Keywords

• Mycobacterium tuberculosis
• Pyrazinamide and moxifloxacin
• Treatment outcome
• Tuberculosis