Plasmid-borne or chromosomally mediated resistance by Tn7 is the most common response to ubiquitous use of trimethoprim

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Abstract
The folic acid analog trimethoprim has been in clinical use for more than 10 years. The use of it in Sweden has doubled in the last 6 to 7 years, and from the distribution statistics it can be calculated that during 1 year 4 to 5% of the population in Sweden are given this drug. The bacterial resistance mechanisms to be found in response to such a selection pressure were investigated in a relatively isolated population in northern Sweden (the county of Jämtland), in which one centrally located bacteriological laboratory serves the area. Trimethoprim-resistant strains were collected during an 8-month period from consecutive specimens of bacteria from the urinary tracts of patients. Among the highly resistant strains of enteric bacteria, trimethoprim resistance mediated by transposon-borne dihydrofolate reductase of type I was found to dominate. The corresponding Tn7-like transposon was found to be localized both on the chromosome of isolated Escherichia coli strains and also on a 50-kilobase IncI transferable plasmid which was found in several different serotypes of E. coli. In two enterobacterial strains, resistance to more than 10(3) micrograms of trimethoprim per ml was furthermore found to be caused by a ca. 80-fold increase in the formation of chromosomal dihydrofolate reductase.