title: Trimethoprim/sulfametrole: evaluation of the available clinical and pharmacokinetic/pharmacodynamic evidence.
abstract: Emergence of resistance to widely used trimethoprim/sulfamethoxazole (TMP/SMX) as well as common adverse events in human immunodeficiency virus (HIV)-infected patients casts interest on combinations of TMP with other sulfonamides. Sulfametrole (SMT) combined with TMP could provide a choice for difficult-to-treat infections, particularly when administered intravenously. The objective of this review was to evaluate the available clinical and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding TMP/SMT, particularly in comparison with TMP/SMX. We reviewed the available evidence retrieved from searches in PubMed/Scopus/Google Scholar and by bibliography hand-searching. In total, 46 eligible studies (most published before 1997) were identified, 7 regarding intravenous (i.v.) TMP/SMT, 24 regarding oral TMP/SMT and 15 providing comparative data for TMP/SMT versus TMP/SMX. The antimicrobial activity of TMP/SMT was similar to TMP/SMX for Gram-positive isolates. A greater percentage of Escherichia coli and Proteus spp. isolates were susceptible to TMP/SMT compared with TMP/SMX. PK/PD data suggest a dosage adjustment of i.v. TMP/SMT in patients with seriously impaired renal function. Four randomised controlled trials and 16 non-comparative studies reported good effectiveness/safety outcomes for oral TMP/SMT in genital ulcers (mainly chancroid), respiratory tract infections and urinary tract infections (UTIs). Moreover, i.v. TMP/SMT was effective against Pneumocystis jiroveci infection in HIV-infected patients, severe pneumonia and UTIs. In one study, hypersensitivity reactions occurred in 18/52 (34.6%) of HIV-infected patients; 2/52 (3.8%) developed psychosis. Gastrointestinal adverse events were mild and rare. Excipients in i.v. TMP/SMT formulations might be less toxic compared with i.v. TMP/SMX formulations, particularly for children. In conclusion, despite the scarcity of contemporary evidence, available data suggest that TMP/SMT could be an alternative treatment option to TMP/SMX, even in serious infections, when administered intravenously.
authors: Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece.
authors: Evridiki K
authors: EK
authors: Vouloumanou
authors: Drosos E
authors: DE
authors: Karageorgopoulos
authors: Petros I
authors: PI
authors: Rafailidis
authors: Argyris
authors: A
authors: Michalopoulos
authors: Matthew E
authors: ME
authors: Falagas
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D006801:Humans; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D013424:Sulfanilamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D016896:Treatment Outcome; D014295:Trimethoprim / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D013424:Sulfanilamides; D014295:Trimethoprim; C012047:sulfametrole