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Journal of Clinical Microbiology, September 2000, p. 3161-3164, Vol. 38, No. 9
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Relationship between Mutations in Dihydropteroate Synthase of Pneumocystis carinii f. sp. hominis Isolates in Japan and Resistance to Sulfonamide Therapy

Takashi Takahashi,1,* Noriaki Hosoya,1,2 Tokiomi Endo,1 Tetsuya Nakamura,3 Hiroyuki Sakashita,4 Kyoko Kimura,5 Kenji Ohnishi,5 Yoshikazu Nakamura,6 and Aikichi Iwamoto1,3

Departments of Infectious Diseases,1 Infectious Diseases and Applied Immunology,3 and Tumor Biology,6 Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Departments of Internal Medicine4 and Infectious Diseases,5 Tokyo Metropolitan Bokutoh General Hospital, Tokyo 130-0022, and Laboratory of Biomedical Chemistry, Department of Applied Chemistry, Tokai University, Kanagawa 259-1292,2 Japan

Received 2 March 2000/Returned for modification 13 April 2000/Accepted 12 June 2000

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 infection (n = 4) or malignant lymphoma (n = 2). This frequency was almost the same as those reported in Denmark and the United States. None of the six patients whose isolates had DHPS mutations were recently exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of sulfa agents but may be incidentally acquired. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n = 4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.


* Corresponding author. Mailing address: Department of Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5336. Fax: 81-3-5449-5427. E-mail: takahata{at}ims.u-tokyo.ac.jp.


Journal of Clinical Microbiology, September 2000, p. 3161-3164, Vol. 38, No. 9
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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