Failure of co-trimoxazole in Pneumocystis carinii infection and mutations in dihydropteroate synthase gene
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)77687-X/abstract
This report describes two HIV-infected patients in whom co-trimoxazole prophylaxis or treatment failed, with detection of Pneumocystis carinii DHPS gene mutations. These findings support concerns that sulphonamide resistance may emerge under prophylactic pressure, threatening the efficacy of standard PCP prevention strategies.
For HIV-infected patients with CD4 counts under 200/μL, life-long co-trimoxazole (trimethoprim-sulphamethoxazole) is standard to prevent Pneumocystis carinii pneumonia (PCP).1 This has raised concerns that P carinii might develop resistance to this useful drug. Sulphamethoxazole targets dihydropteroate synthase (DHPS) and trimethoprim targets dihydrofolate reductase, sequential enzymes in folate metabolism; sulphamethoxazole accounts for nearly all the activity in animal models. Recently Kazanjian et al identified mutations in the human P carinii DHPS gene which were found mostly in patients previously receiving prophylaxis with a sulphonamide or with dapsone.2 However, they did not determine whether patients had actually had prophylaxis broken through. We report two HIV-infected patients in whom prophylaxis or treatment with co-trimoxazole failed, and in whom we identified DHPS mutations.
