title: A randomized trial of N-acetylcysteine for prevention of trimethoprim-sulfamethoxazole hypersensitivity reactions in Pneumocystis carinii pneumonia prophylaxis (CTN 057). Canadian HIV Trials Network 057 Study Group.
abstract: Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites 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 decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients 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 Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, 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 with HIV infection.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada. swalmsley@torhosp.toronto.on.ca
authors.forename: S L
authors.initials: SL
authors.lastname: Walmsley
authors.forename: S
authors.initials: S
authors.lastname: Khorasheh
authors.forename: J
authors.initials: J
authors.lastname: Singer
authors.forename: O
authors.initials: O
authors.lastname: Djurdjev
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D011322:Primary Prevention; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D016166:Free Radical Scavengers; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000111:Acetylcysteine