A randomized trial of N-acetylcysteine for prevention of trimethoprim-sulfamethoxazole hypersensitivity reactions in Pneumocystis carinii pneumonia prophylaxis (CTN 057)

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolit es that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decrease d ability to scavenge these metabolites. Two hundred and thirty-eight patie nts were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg , sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneu mocystis carinii pneumonia prophylaxis. Forty-five patients had to disconti nue TMP-SMX within 2 months because of fever, rash, or pruritus including 2 5 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patie nts (21%) who were randomized to TMP-SMX and N-acetylcysteine. The differen ce between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%) . No independent association was found with the hypersensitivity reaction a nd age, gender, race, HIV risk factor, prior AIDS, concurrent use of flucon azole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients wit h HN infection.