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Antimicrobial Agents and Chemotherapy, November 2009, p. 4835-4839, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00541-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in Vietnam{triangledown}

Duong Duy An,1 Nguyen Thi Hong Duyen,1 Nguyen Thi Ngoc Lan,2 Dai Viet Hoa,2 Dang Thi Minh Ha,1,2 Vo Sy Kiet,1 Do Dang Anh Thu,1 Nguyen Van Vinh Chau,1,4 Nguyen Huy Dung,2 Dinh Ngoc Sy,5 Jeremy Farrar,1,3 and Maxine Caws1,3*

Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5, Ho Chi Minh City, Vietnam,1 Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases, 120 Hung Vuong, District 5, Ho Chi Minh City, Vietnam,2 Centre for Tropical Medicine, Churchill Hospital, Old Road, Headington, Oxford, United Kingdom,3 Hospital for Tropical Diseases, 190 Ben Ham Tu, Ho Chi Minh City, Vietnam,4 Vietnam National TB Control Programme, 463 Hoang Hoa Tham Street, Ba Dinh, Ha Noi, Vietnam5

Received 22 April 2009/ Returned for modification 10 June 2009/ Accepted 19 August 2009

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 µg/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.

* Corresponding author. Mailing address: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5, Ho Chi Minh City, Vietnam. Phone: (84 8) 8384013. Fax: (84 8) 8353904. E-mail: mcaws{at}hotmail.com

{triangledown} Published ahead of print on 31 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4835-4839, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00541-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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