Mechanisms of trimethoprim resistance in enterobacteria isolated in Finland

Dihydrofolate reductases (DHFR) were studied in two groups of trimethoprim (TMP)-resistant Enterobacteria, isolated in Turku, Finland. The first group consisted of six strains with a high level of TMP resistance (MIC greater than 1,000 mg/l) and all of them were found to harbour an additional TMP-insensitive DHFR thought to be responsible for the high degree of resistance. Three Proteus mirabilis strains in this group synthesized chromosomal reductases with reduced TMP sensitivity as well. A second group of six strains, exhibiting MIC values for TMP between 16 and 512 mg/l was seen to be resistant by the production of a chromosomally altered TMP-insensitive DHFR, produced either in normal or slightly elevated amounts. With one exception these strains were all fully susceptible to sulfadiazine and strong synergism with TMP was present. Resistance to nalidixic acid was also frequently observed in this group. In conclusion, three different basic mechanisms were found to be responsible for TMP resistance in Enterobacteria from Finland and these were seen to occur not only independently but also simultaneously in the same strain.