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.