title: Beijing genotype of Mycobacterium tuberculosis is significantly associated with high-level fluoroquinolone resistance in Vietnam.
abstract: Consecutive fluoroquinolone (FQ)-resistant isolates (n = 109) identified at the Pham Ngoc Thach Hospital for Tuberculosis, Ho Chi Minh City, Vietnam, were sequenced in the quinolone resistance-determining regions of the gyrA and gyrB genes and typed by large sequence polymorphism typing and spoligotyping to identify the Beijing genotype of Mycobacterium tuberculosis. Beijing genotype prevalence was compared with 109 consecutive isolates from newly presenting patients with pulmonary tuberculosis from the hospital outpatient department. Overall, 82.6% (n = 90/109) of isolates had mutations in gyrAB. Nine novel mutations were identified in gyrB (S486F, N538T, T539P, D500A, D500H, D500N, G509A, E540V, and E540D). The influence of these novel gyrB mutations on FQ resistance is not proven. The Beijing genotype was significantly associated with FQ resistance (odds ratio [OR], 2.39 [95% confidence interval {CI}, 1.34 to 4.25]; P = 0.003). Furthermore, Beijing genotype FQ-resistant isolates were significantly more likely than FQ-resistant isolates of other genotypes to have gyrA mutations (OR, 7.75 [95% CI, 2.84 to 21.15]; P = 0.0001) and high-level (>8 microg/ml) FQ resistance (OR, 11.0 [95% CI, 2.6 to 47.0]; P = 0.001). The underlying mechanism of the association of the Beijing genotype with high-level FQ resistance in this setting remains to be determined. The association of the Beijing genotype with relatively high-level FQ resistance conferred by specific gyrA mutations reported here is of grave concern given the epidemic spread of the Beijing genotype and the current hopes for shorter first-line treatment regimens based on FQs.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Duy An
authors.initials: DA
authors.lastname: Duong
authors.forename: Thi Hong Duyen
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Thi Ngoc Lan
authors.initials: TN
authors.lastname: Nguyen
authors.forename: Viet Hoa
authors.initials: VH
authors.lastname: Dai
authors.forename: Thi Minh Ha
authors.initials: TM
authors.lastname: Dang
authors.forename: Sy Kiet
authors.initials: SK
authors.lastname: Vo
authors.forename: Dang Anh Thu
authors.initials: DA
authors.lastname: Do
authors.forename: Van Vinh Chau
authors.initials: VV
authors.lastname: Nguyen
authors.forename: Huy Dung
authors.initials: HD
authors.lastname: Nguyen
authors.forename: Ngoc Sy
authors.initials: NS
authors.lastname: Dinh
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Maxine
authors.initials: M
authors.lastname: Caws
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D027081:DNA Gyrase / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D027081:DNA Gyrase