Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in Vietnam
Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in Vietnam
复制标题
DOI：
10.1128/aac.00541-09
复制
发表时间：
2009-11-01
影响因子：
4.9
通讯作者：
Caws, Maxine
中科院分区：
文献类型：
--
作者：
An, Duong Duy;Duyen, Nguyen Thi Hong;Caws, Maxine
对越南胡志明市范玉塔医院结核病科分离的109株耐氟喹诺酮（FQ）结核分枝杆菌进行gyrA和gyrB基因喹诺酮耐药决定区测序，并通过大序列多态性分型和间隔寡核苷酸分型确定北京基因型。北京基因型流行率与109个来自医院门诊新发肺结核患者的连续分离株进行比较。总体而言，82.6%（n = 90/109）的分离株在gyrAB中存在突变。在gyrB中鉴定出9个新突变（S486 F、N538 T、T539 P、D500 A、D500 H、D500 N、G509 A、E540 V和E540 D）。这些新的gyrB突变对FQ耐药的影响尚未得到证实。北京基因型与FQ耐药显著相关（比值比[OR]，2.39 [95%置信区间{CI}，1.34至4.25]; P = 0.003）。此外，北京基因型的耐药菌株比其他基因型的耐药菌株更可能具有gyrA突变（OR，7.75 [95%CI，2.84至21.15]; P = 0.0001）和高水平（> 8 μ g/ml）的FQ耐药（OR，11.0 [95%CI，2.6至47.0]; P = 0.001）。在这种情况下，北京基因型与高水平FQ抗性相关的潜在机制仍有待确定。考虑到北京基因型的流行性传播以及目前对基于FQs的较短一线治疗方案的希望，本文报道的北京基因型与特定gyrA突变所赋予的相对高水平FQ耐药的关联是严重关切的。
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 mu g/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.