Association between a specific Pneumocystis jiroveci dihydropteroate synthase mutation and failure of pyrimethamine/sulfadoxine prophylaxis in human immunodeficiency virus-positive and -negative patients

To investigate the possible association between different prophylactic sulfa drugs and the genotype of the Pneumocystis jiroveci dihydropteroate synthase ( DHPS) gene, we examined DHPS polymorphisms in clinical specimens from 158 immunosuppressed patients ( 38 HIV-negative and 120 HIV-positive), using polymerase chain reaction-single-strand conformation polymorphism. Fifty-seven (36.1%) of 158 patients were infected with a mutant DHPS genotype. All patients who developed P. jiroveci pneumonia (PcP) while receiving pyrimethamine/sulfadoxine (PM/SD) prophylaxis (n=14) had a strain harboring DHPS with an amino acid change at position 57 ( Pror-->Ser). This mutation was only present in 20 ( 14%) of 144 patients not receiving prophylaxis (P < .001). Hospitalization in a specific hospital was an independent risk factor for having P. jiroveci harboring the same DHPS mutation, which indirectly supports that interhuman transmission may affect the dissemination of the mutant strains.