SUMMARY Thymidine at levels as low as 005 mg/l reduces the activities of sulphamethoxazole and trimethoprim and their combination in vitro. Using a biological assay procedure, levels of thymidine greater than this were interpreted as being present in urine. The addition of sulphamethoxazole and trimethoprim, singly or in combination, to urine obtained from patients with urinary tract infections showed that all the antibacterial effect towards sensitive organisms was due to the trimethoprim component. It is suggested that trimethoprim should replace the combination co-trimoxazole for the treatment of some lower urinary tract infections, and that laboratory media, if they are to resemble the clinical environment, should contain thymidine.

No abstract

There is probably, however, one serious drawback in the use of MIC methods to report antibiotic sensitivity. Under certain conditions (particularly when a dilute inoculum is used) the assessment of sensitivity obtained by MIC methods will fail to take into account the production of certain enzymes.

THE USE of antimicrobial agents in combination continues to be evaluated for the ability to suppress the appearance of resistant bacterial mutants and to produce a synergistic effect in vivo. Both these properties were thought to apply to the use of a fixed combination of trimethoprim and sulphamethoxazole (co-trimoxazole). However, in the treatment of lower urinary-tract infections, there is evidence of the therapeutic effect being so dominated by trimethoprim that the potential synergistic effect between trimethoprim and sulphamethoxazole is not realised during clinical use (Brumfitt and Pursell, 1972 Grey and Hamilton-Miller, 1977;Tuomisto, Kasanen and Renkonen, 1977); this preparation (co-trimazine) contains in each tablet 90 mg of trimethoprim and 410 mg of sulphadiazine and the recommended dosage is one tablet twice daily. Any advantage for such a combination over the use of individual components should be clearly established because the toxic effects of sulphadiazine and trimethoprim in a fixed combination seem likely to be greater than when they are used singly. During therapy, urine concentrations of active sulphadiazine can be anticipated to be higher than those of sulphamethoxazole on account of the lesser acetylation and higher solubility of sulphadiazine (e.g., Tuomisto et al., 1977). Thus, while we have previously failed to detect any synergistic effects between sulphamethoxazole and trimethoprim when added in therapeutic levels to naturally infected urine (Stokes and Lacey, 1978), sulphadiazine might be present in sufficient amounts for synergy to occur. Therefore, experiments were performed to determine whether such synergy had occurred. This paper describes the antibacterial effects of these agents in urine and in blood, and investigation of the possibility that trimethoprim resistance appears during exposure of organisms to trimethoprim in urine. MATERIALS AND METHODSCulture media, general bacteriological methods and sensiticity testing were as as described by Stokes and Lacey (1978).Infected urine. Two types of infected urine were used. The first type consisted of small pools of infected urine, 6-8 collections of 10-25 ml each, at pH 64-7.4; this was defined as "pooled urine" and was used to dilute possible interfering substances in a sample. The second type of

Good cytological detail, especially good nuclear detail, is obviously of value to the histopathologist when examining sections of lymph nodes and, in particular, when examining lymph nodes from patients suspected of having a malignant lymphoma.In an attempt to improve the nuclear detail of lymph node sections, we Requests for reprints to: