General survey of trimethoprim combinations in the treatment of urinary tract infections

The properties of trimethoprim (TM), reviewed here, show it to be an excellent antimicrobial agent in its own right. However, with very few exceptions, TM has been made available clinically only in combination with a sulphonamide, usually sulphamethoxazole (SMX). We present evidence to suggest that the decision so to restrict the availability of TM was mistaken. Synergy between TM and SMX can be shown clearly in vitro, but there is no evidence from clinical trials that it plays a significant therapeutic role in urinary infections. Also, there is no evidence that combining the two antibiotics suppresses the emergence of resistance. Recently, sulphonamides other than SMX have been proposed as partners for TM, mainly on pharmacokinetic grounds. Compounds other than sulphonamides may also be logical partners for TM: we have made extensive studies on TM + rifampicin, for instance, and have obtained excellent results in certain clearly-defined patient groups. Only clinical trials of these new combinations will reveal whether they are superior to TM/SMX. There is already sufficient evidence to suggest that TM alone will be as effective as, and more acceptable than, TM/SMX. We propose that further large-scale clinical trials with TM alone be carried out, both to treat acute urinary infections and in prophylaxis.