Bactericidal activity of trimethoprim alone and in combination with sulfamethoxazole on susceptible and resistant Escherichia coli K-12.

The combined effects of trimethoprim and sulfamethoxazole on the viability of Escherichia coli K-12 and resistant strains possessing resistance plasmids were examined in minimal medium. When methionine, glycine, and adenine were present, sulfamethoxazole could enhance trimethoprim activity against E. coli K-12 so that the combination was bactericidal.

Co-trimoxazole susceptibility tests improved with separate trimethoprim and sulfamethoxazole disks.

It is impossible to test accurately bacterial susceptibility to the trimethoprim-sulfamethoxazole combination co-trimoxazole with a single combined susceptibility disk. However, a variety of factors still affect the result even when separate trimethoprim and sulfamethoxazole disks are used. Experiments with separate disks showed that the optimum conditions for testing the susceptibilities of enterobacteria to these drugs were to flood-seed an agar plate with an inoculum of 10(4) to 10(5) organisms per ml, take off the excess liquid, and place a disk of 1 microgram of trimethoprim and another of 50 micrograms of sulfamethoxazole on the surface of the agar with their centers exactly 25 mm apart.

Co-trimoxazole sensitivity testing: comparison of separate and combined disk agar diffusion techniques.

Five hundred and seven strains of bacteria isolated from the urine of patients with significant bacteriuria (more than 10(8) colony-forming units per litre) were tested for sensitivity to co-trimoxazole by the agar diffusion technique. Each organism was tested with a combined disk containing trimethoprim and sulphamethoxazole in a primary sensitivity test and, at a standardised inoculum, with both a combined disk and separate disks of trimethoprim and sulphamethoxazole. The results show that combined disk testing does not always indicate the sensitivity patterns of the organisms being tested.

R-factor mediated trimethoprim resistance: result of two three-month clinical surveys.

All urinary tract isolates were monitored in the Whittington Hospital, London for trimethoprim resistance over a three-month period in 1975; this survey was repeated 18 months later in 1977. In the later survey the incidence of trimethoprim resistance had increased significantly, and the proportion of strains carrying R-factors conferring trimethoprim resistance had nearly doubled. The pattern of resistances associated with R-factor trimethoprim resistance also changed betweeen these two surveys.

R-factor mediated dihydrofolate reductases which confer trimethoprim resistance.

Six different R-factors conferring trimethoprim resistance had been isolated from a variety of sources. The trimethoprim-resistant dihydrofolate reductases (EC 1.5.

The purification and properties of the trimethoprim-resistant dihydrofolate reductase mediated by the R-factor, R388.

The R-factor R388 mediates the production of a trimethoprim-resistant dihydrofolate reductase. This enzyme has a different molecular weight and pH profile to the trimethoprim-sensitive enzyme of the Escherichia coli host. The R-factor mediated enzyme was separated completely from the host E.

Trimethoprim action and its analogy with thymine starvation.

In a minimal medium, trimethoprim is merely bacteriostatic on the prototroph Escherichia coli 114. The drug was bactericidal when the amino acids methionine and glycine, plus a purine or purine nucleoside, were also present. This response could be reversed completely when thymine and lysine were added to the culture.