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Journal of Clinical Microbiology, July 2008, p. 2263-2268, Vol. 46, No. 7
0095-1137/08/$08.00+0     doi:10.1128/JCM.00561-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Biological and Molecular Characteristics of Mycobacterium tuberculosis Clinical Isolates with Low-Level Resistance to Isoniazid in Japan

Chiyoji Abe,^1* Ikuo Kobayashi,¹ Satoshi Mitarai,² Masako Wada,³ Yoshiko Kawabe,⁴ Tetsuya Takashima,⁵ Katsuhiro Suzuki,⁶ Li-Hwei Sng,⁷ Suxing Wang,⁷ Hla Hla Htay,⁷ and Hideo Ogata⁸

Fukushima Laboratory, Nippon Becton Dickinson Diagnostic Systems, Fukushima, Japan,¹ Mycobacterium Reference Center,² Department of Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan,³ Department of Respiratory Medicine, National Hospital Organization Tokyo National Hospital, Tokyo, Japan,⁴ Department of Respiratory Medicine, Osaka Prefectural Medical Center for Respiratory Allergic Disease, Osaka, Japan,⁵ Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, Osaka, Japan,⁶ Central Tuberculosis Laboratory, Department of Pathology, Singapore General Hospital, Singapore,⁷ Department of Respiratory Medicine, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan⁸

Received 25 March 2008/ Returned for modification 3 May 2008/ Accepted 18 May 2008

We reevaluated the BACTEC MGIT 960 antimicrobial susceptibility testing system (MGIT 960 AST) by using 1,112 isolates of Mycobacterium tuberculosis. When the results of MGIT 960 AST were compared with that of the proportion method using Ogawa medium (Ogawa PM), discrepant results were obtained for 30 strains with isoniazid, all resistant by MGIT 960 AST but susceptible by Ogawa PM. For 93% of the strains that produced discrepant results, the MIC was 0.4 or 0.8 µg/ml, showing resistance by the proportion method using Middlebrook agar plates. Furthermore, it was also established by analyses of the katG and inhA genes that strains resistant only by MGIT 960 AST have a low level of isoniazid (INH) resistance, indicating that MGIT 960 AST is a reliable method. Ninety-six strains were resistant to 0.1 µg/ml INH by MGIT 960 AST. When they were divided into three groups, Low-S (susceptible at 0.2 µg/ml), Low-R (resistant at 0.2 µg/ml), and High-R (resistant at 1.0 µg/ml), by Ogawa PM, 43.3% of the Low-S strains had mutations in the promoter region of inhA and no mutations were detected in katG codon 315, while 61.7% of the High-R strains had katG codon 315 mutations or a gross deletion of katG. These results suggest that mutations in inhA are associated with low-level resistance to INH and katG codon 315 mutations are associated with high-level resistance to INH. In addition, the analyses demonstrated some relationship of mutations in the inhA gene with ethionamide resistance for the Low-S strains, but not for the High-R strains.

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* Corresponding author. Mailing address: Fukushima Laboratory, Nippon Becton Dickinson Diagnostic Systems, 1 Gotanda, Tsuchifune, Fukushima 960-2152, Japan. Phone: 81-24-594-1623. Fax: 81-24-594-1688. E-mail: abe_chiyoji{at}yahoo.co.jp

Published ahead of print on 28 May 2008.

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Journal of Clinical Microbiology, July 2008, p. 2263-2268, Vol. 46, No. 7
0095-1137/08/$08.00+0     doi:10.1128/JCM.00561-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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