Trimethoprim: a review of its antibacterial activity, pharmacokinetics and therapeutic use in urinary tract infections

Trimethoprim, which has been widely available for several years in combination with sulphamethoxazole as co-trimoxazole, is now available for use alone in the treatment of acute uncomplicated urinary tract infections. Trimethoprim, which is active against a wide range of Gram-positive and Gram-negative aerobic bacteria, is readily absorbed by the oral route and is widely distributed in body fluids and tissues. In therapeutic trials, trimethoprim 200 to 400mg daily has been shown to be comparable in efficacy with co-trimoxazole, ampicillin 2g, cephalexin 2g, oxolinic acid 1.5g and nitrofurantoin 200mg daily in the treatment of acute urinary tract Infection. Similarly, in long term prophylaxis of recurrent urinary tract Infection, trimethoprim 100mg daily given as a single dose at night was comparable with nitrofurantoin 50 to 100mg, methenamine 1g, oxolinic acid 375mg or co-trimoxazole (80mg trimethoprim/400mg sulphamethoxazole) each given as a single daily dose. Emergence of acquired resistance has been infrequent during years of therapeutic use of co-trimoxazole. Nevertheless, results of serial laboratory surveys suggest that resistance to trimethoprim among enterobacteria is increasing. However, at present, there is no conclusive evidence that there will be a more rapid increase following the introduction of trimethoprim for use alone in the treatment of urinary tract infections. At the dosages used, trimethoprim has generally been well tolerated and in studies comparing it with co-trimoxazole overall, skin rashes and gastrointestinal upset have occurred less frequently with trimethoprim than with co-trimoxazole.