gene mutations in rifampin-resistant isolates from rural areas of Zhejiang, China.

Objective: The aim was to analyze genetic mutations in the gene of rifampin-resistant isolates (RIF-MTB) from Zhejiang, China.

Methods: We prospectively analyzed RIF-associated mutations in 13 rural areas of Zhejiang. Isolates were subjected to species identification, phenotype drug susceptibility testing (DST), DNA extraction, and gene sequencing.

Results: A total of 103 RIF isolates were identified by DST (22 RIF only, 14 poly-drug resistant, 49 multidrug resistant, 13 pre-extensively drug resistant [pre-XDR], and 5 extensively drug resistant [XDR]) from 2152 culture-positive sputum specimens. Gene sequencing of showed that the most frequent mutation was S450L (37.86%, 39/103); mutations P280L, E521K, and D595Y were outside the rifampicin resistance-determining region (RRDR) but may be associated with RIF. Mutations associated with poly-drug resistant, pre-XDR, and XDR TB were mainly located at codon 445 or 450 in the RRDR.

Conclusions: The frequency of RRDR mutation in Zhejiang is high. Further studies are needed to clarify the relationships between RIF and the TTC insertion at codon 433 in the RRDR and the P280L and D595Y mutations outside the RRDR.