The emergence and mechanisms of trimethoprim resistance in Escherichia coli isolated from outpatients in Finland.

Trimethoprim (TMP), either alone or in combination with sulphonamides, is commonly used for treating urinary tract infections. In Finland, TMP alone has been in clinical use since 1973. TMP resistance in the major outpatient urinary tract pathogen, Escherichia coli, increased during 1978-1988 from 5% to 16% in the Turku area, during 1980-1988 from 3% to 19% in the Helsinki area and also during 1980-1988 from 3% to 14% in the Rovaniemi area. The majority (91%) of TMP-resistant strains were highly-resistant to TMP (MIC greater than or equal to 1024 mg/l). The most common (57%) TMP resistance gene, detected by DNA hybridization, was the type I dihydrofolate (DHFR) gene. The type II DHFR genes were found in less than 3% of the strains studied. No positive hybridizations were detected with the type III DHFR probe, and only a few positive hybridizations were found with the type V DHFR probe. Forty percent of the isolates did not hybridize with any of the DHFR probes used, suggesting additional unknown resistance mechanisms responsible for the high-level TMP resistance. These unknown TMP resistance mechanisms, together with the type I DHFR-mediated resistance, were responsible for the increase of TMP resistance among the E. coli strains studied.