Trimethoprim and sulfonamide resistance

Trimethoprim (TMP) and sulfonamides (SULs) are synthetic antibacterial agents. The first SUL compounds were used in 1932, whereas TMP is a relatively new compound first used in 1962 in England (69). Since 1968, TMP has been used in combination with SULs because the combination of TMPSULs was supposed to be synergistic in vitro (18). However, clinical experience suggests that TMP-SUL combinations have no clear synergism in vivo (2, 16, 112). In the 1970s, TMP alone came into use, first for the prophylaxis of urinary tract infections and later for the treatment of acute urinary tract infections as well (81). TMP and SULs share both a wide antibacterial spectrum including common urinary tract pathogens (Escherichia coli and other members of the family Enterobacteriaceae), respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and in combination, Moraxella catarrhalis), skin pathogens (Staphylococcus aureus), as well as certain enteric pathogens (E. coli and Shigella spp.). Because of the wide range of clinical indications, TMP-SUL combinations have been used extensively everywhere in the world. In addition, both compounds are relatively inexpensive, a fact that allows for the use of these drugs outside of developed countries. Today, the most important fear is the development of bacterial resistance to TMP and SULs. To counter bacterial resistance it is essential to understand the molecular background of resistance mechanisms. Analysis of TMP and SUL resistance determinants in clinical bacteria has already revealed new recombination mechanisms that have an impact on spread of the resistance in general. As synthetic antimicrobial agents, TMP and SULs are also examples of agents that bacteria have not met previously, and to which they can develop resistance; this excludes resistance mechanisms related to antibiotic-producing organisms. In this minireview, we describe the current knowledge of TMP and SUL resistance in major bacterial pathogens and review the TMP and SUL resistance mechanisms.

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