Incidence and mechanisms of resistance to trimethoprim in clinically isolated gram-negative bacteria.

Over an 18-month period (October 1973 to April 1975), 133 strains of gram-negative bacteria with acquired resistance to trimethoprim (TM) were isolated from infected urines cultured at the Royal Free Hospital. The overall frequency of resistance was 3.2%. A disproportionately high number of resistant strains (63.1%) were Kebsiella aerogenes. Resistance to TM mediated by R plasmids occurs infrequently (9% of all resistant strains); the majority of TMR plasmids isolated belonged to one incompatability group (W). Chromosomally mediated resistance to TM in most Escherichia coli and K. aerogenes strains appears to be due mainly to production of a dihydrofolate reductase with a reduced susceptibility to TM. In some strains, increased activity of the DHFR was also a contributing factor. Increase in enzyme level alone was only great enough to account for the level of resistance to TM in a small number of cases.