Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis.

ABSTRACT: Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Emergence of P. jirovecii drug resistance has been suggested by the association between failure of prophylaxis with sulfa drugs and mutations in DHPS. However, data on the occurrence of mutations in DHFR, the target of trimethoprim and pyrimethamine, are scarce. We examined polymorphisms in P. jirovecii DHFR from 33 patients diagnosed with P. jirovecii pneumonia who were receiving prophylaxis with a DHFR inhibitor (n = 15), prophylaxis without a DHFR inhibitor (n = 11), or no prophylaxis (n = 7). Compared to the wild-type sequence present in GenBank, 19 DHFR nucleotide substituti

SUBMITTER: Nahimana A 

PROVIDER: S-EPMC525445 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature