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Biomedical subjects

R Steen

Publications and source records attributed to R Steen.

38 records · Page 3Linked to original sources

Correlation of drug utilization data for trimethoprim in a defined population with patterns of resistance among bacteria causing urinary tract infections.

Data from the continuous monitoring of outpatient prescriptions performed since 1970 among the inhabitants in the county of Jämtland were used to correlate the individual utilization of the antibacterial drug trimethoprim to the occurrence of resistance to this drug among pathogenic bacteria isolated in samples from the same population. There was a good correlation between the use of trimethoprim among female and male patients of different age groups and the occurrence of drug resistant bacteria in samples from the corresponding groups of patients. From total distribution data it was estimated that approximately 3% of the population received trimethoprim in 1984. In the oldest age groups one third of the county population was exposed to trimethoprim during a 6-year period. That this intensive use of the drug exerted a pronounced selection pressure for resistant strains in the population at large is indicated by the finding that one third of the patients harbouring resistant bacterial strains had never been treated with trimethoprim. This is interpreted as a reflection of trimethoprim resistance selected to such a ubiquity that it is spread independently of individual drug therapy.

Bacterial Infections↗

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

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.

Chromosomes, Bacterial↗