Dihydropteroate Synthase Gene Mutations in Pneumocystis and Sulfa Resistance

摘要

Pneumocystis pneumonia (PCP) remains a majorcause of illness and death in HIV-infected persons. Sulfadrugs, trimethoprim-sulfamethoxazole (TMP-SMX), anddapsone are mainstays of PCP treatment and prophylaxis.While prophylaxis has reduced the incidence of PCP, itsuse has raised concerns about development of resistantorganisms. The inability to culture human Pneumocystis,Pneumocystis jirovecii, in a standardized culture systemprevents routine susceptibility testing and detection of drugresistance. In other microorganisms, sulfa drug resistancehas resulted from specific point mutations in the dihy-dropteroate synthase (DHPS) gene. Similar mutationshave been observed in P. jirovecii. Studies have consistent-ly demonstrated a significant association between the useof sulfa drugs for PCP prophylaxis and DHPS gene muta-tions. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatmentremains unclear. We review studies of DHPS mutations inP. jirovecii and summarize the evidence for resistance tosulfamethoxazole and dapsone