Relationship between mutations in dihydropteroate synthase of Pneumocystiscarinii f. sp hominis isolates in Japan and resistance to sulfonamide therapy

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneum ocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patien ts 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 pati ents. The underlying diseases for these six patients were human immunodefic iency virus type 1 infection (n = 4) or malignant lymphoma (n = 2), This fr equency was almost the same as those reported in Denmark and the United Sta tes. None of the six patients whose isolates had DHPS mutations were recent ly exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of su lfa agents but may be incidentally acquired. Co-trimoxazole treatment faile d more frequently in patients whose isolates had DHPS mutations than in tho se 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 fa ilures of co-trimoxazole treatment for PCP.