Disease relevance of sulfamethoxazole

• Seventeen of the 80 patients receiving a placebo acquired P. carinii pneumonitis, whereas none of the 80 given 150 mg of trimethoprim and 750 mg of sulfamethoxazole per square meter per day had the infection P less than 0.01) [1].
• Sulfamethoxazole and other sulfa drugs are moderately potent inhibitors of Escherichia coli dihydrofolate reductase [2].
• Three vs 10 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis [3].
• Sixty patients with a new diagnosis of Kaposi's sarcoma and no history of opportunistic infections were randomly assigned to receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice per day or no therapy [4].
• All case-patient isolates were phage definitive type 104 (DT104) (n = 10) or DT104b (n = 12), and 20 (91%) were resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline [5].

High impact information on sulfamethoxazole

• Three vs 10 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis [6].
• Thirty-two women with recurrent urinary tract infections were treated after eradication of existing infections with a mixture of 40 mg of trimethoprim and 200 mg of sulfamethoxazole thrice weekly at bedtime for six months [7].
• The stimulation of four CD4(+) and two CD8(+) sulfamethoxazole-specific T cell clones by different antigen-presenting cells (APC) was measured both by proliferation and cytolytic assays [8].
• These features are best explained by a direct, noncovalent binding of sulfamethoxazole to the MHC-peptide complex [8].
• The clones were specific for sulfamethoxazole without cross-reaction to other sulfonamides [8].

Chemical compound and disease context of sulfamethoxazole

• Trimethoprim/sulfamethoxazole is now considered the drug of choice for shigellosis due to the presence of ampicillin-resistant Shigella strains in most regions of the world [9].
• Vibrio cholerae O139, the first non-O1 serogroup of V. cholerae to give rise to epidemic cholera, is characteristically resistant to the antibiotics sulphamethoxazole, trimethoprim, chloramphenicol and streptomycin [10].
• In order to compare the effectiveness of various therapies for acute gastroenteritis, patients were treated for five days with either norfloxacin, 400 mg twice daily, norfloxacin, 400 mg three times a day, or trimethoprim/sulfamethoxazole, (160 mg/800 mg) twice daily [11].
• A multicenter study of lomefloxacin and trimethoprim/sulfamethoxazole in the treatment of uncomplicated acute pyelonephritis [12].
• Periodic intravenous gammaglobulin was more effective than conventional therapy (trimethoprim/sulfamethoxazole and pentamidine) in achieving clinical and immunologic improvement and reduction of serum lactate dehydrogenase activity in patients with Pneumocystis carinii pneumonitis [13].

Biological context of sulfamethoxazole

• Here, we examine KCNE2 in 98 patients with drug-induced LQTS, identifying three individuals with sporadic mutations and a patient with sulfamethoxazole-associated LQTS who carried a single-nucleotide polymorphism (SNP) found in approximately 1.6% of the general population [14].
• The labeling of liver extra-mitochondrial acetyl-CoA was investigated in isolated rat livers perfused with [2-(13)C]acetate, [1-(13)C]octanoate, or [1,2,3,4-(13)C4]docosanoate and with drugs that undergo acetylation (phenylaminobutyrate, paraaminobenzoate, and sulfamethoxazole; singly or in combination) [15].
• Sulfapyridine (10 micrograms/ml) also selectively inhibited neutrophil chemotaxis to F-met-leu-phe; however, sulfamethoxazole and sulfisoxazole did not affect chemotaxis [16].
• Coadministration did not significantly alter the pharmacokinetics of trimethoprim or sulfamethoxazole [17].
• Covalent binding of the nitroso metabolite of sulfamethoxazole leads to toxicity and major histocompatibility complex-restricted antigen presentation [18].

Anatomical context of sulfamethoxazole

• The purpose of this study was to investigate how sulfamethoxazole is presented in an immunogenic form to sulfamethoxazole-specific T cell clones [8].
• Lymphocyte transformation tests demonstrated sensitized lymphocytes against trimethoprim but not sulfamethoxazole [19].
• Significant levels of trimethoprim and sulfamethoxazole were easily quantitated in the cerebrospinal fluid during therapy [20].
• Ciprofloxacin versus trimethoprim/sulfamethoxazole for prophylaxis of bacterial infections in bone marrow transplant recipients: a randomized, controlled trial [21].
• Trimethoprim did not appear to be as protective as trimethoprim/sulfamethoxazole when the granulocyte count was less than 100/mm3 [22].

Associations of sulfamethoxazole with other chemical compounds

• Sulfathiazole, sulfamethoxazole, and sulfamethazine, with 50% inhibitory concentrations (IC50's) of 1.7, 2.7, and 5.7 microM, respectively, represent the most potent of this class of inhibitors [23].
• Eighty patients treated with standard-dose trimethoprim-sulfamethoxazole (trimethoprim, < or = 320 mg/d; sulfamethoxazole, < or = 1600 mg/d) composed the treatment group; 25 patients treated with other antibiotic agents served as the control group [24].
• Inhibition of cytokine production and interference in IL-2 receptor-mediated Jak-Stat signaling by the hydroxylamine metabolite of sulfamethoxazole [25].
• Drugs like sulfamethoxazole (SMX) or lidocaine can be presented to specific human alphabeta+ T cell clones (TCC) by undergoing a noncovalent association with MHC-peptide complexes on HLA-matched APCs [26].
• Safety of dapsone as Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with allergy to trimethoprim/sulfamethoxazole [27].

Gene context of sulfamethoxazole

• It also carried the sul1 gene for sulfamethoxazole resistance and a 1-kb class I integron bearing aadA for streptomycin resistance [28].
• With concentrations ranging from 50 to 500 microM, sulfamethoxazole was a selective inhibitor of CYP2C9-mediated tolbutamide hydroxylation in human liver microsomes and recombinant CYP2C9, with apparent IC(50) (K(i)) values of 544 microM (271 microM) and 456 microM, respectively [29].
• Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively [29].
• However, high FOL1 expression levels resulted in increased susceptibility to sulfamethoxazole in pABA free media [30].
• Exposure of mice to the nitroso metabolite of sulfamethoxazole stimulates interleukin 5 production by CD4+ T-cells [31].

Analytical, diagnostic and therapeutic context of sulfamethoxazole

• Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS [4].
• Minimum inhibitory concentrations of sulphamethoxazole and eight other antimicrobials were determined [32].
• Immunologic tests revealed specific antibodies of the immunoglobulin G class but not of the immunoglobulin E class against sulfamethoxazole, and in particular against trimethoprim [19].
• The current report describes two cases of severe, prolonged cholestasis after treatment with trimethoprim sulfamethoxazole; intractable pruritus and abnormal liver test results lasted for 1-2 years after discontinuation of the drug [33].
• Oral trimethoprim/sulfamethoxazole in attempt to prevent infection after induction chemotherapy for acute leukemia [34].

References