Development of sulphonamide-trimethoprim combinations for urinary tract infections

Abstract

Plasma half life and in vitro activity were major criteria for selection of sulphonamides which are likely to give a strong synergistic action with trimethoprim in vivo. On the basis of literature data six sulphonamides, sulphadiazine, sulphachloropyridazine, sulphamethoxazole, sulphaisodimidine, sulphamerazine and sulphamethomidine appeared particularly suitable for combination with trimethoprim. An investigation of the activity in vitro of these compounds and their combinations with the latter against clinically isolated, sulphonamide-sensitive Klebsiella-Enterobacter and Escherichia coli strains showed optimal synergy at trimethoprim-sulphonamide ratios between 1:10 and 1:40, but that appreciable mutual potentiation occurred within a rather broad range of concentration ratios. Limited experiments indicated that synergy occurs less frequently and is less pronounced against sulphonamide resistant bacteria. The different sulphonamides behaved rather similarly in their combinations with trimethoprim, and in order to find the best sulphonamide, detailed comparisons of the pharmacokinetic properties of the different combinations are necessary.

Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink (Neovison vison)

“…For this purpose, the optimal ratio between TMP and SDZ for exerting maximum synergy against target pathogens should be considered. For E. coli , Ekström, Forsgren, Örtengren, and Bergan (1979) quantified the effect of TMP and SDZ using in vitro checkerboard assays and found an optimal synergistic effect using a 1:10–1:20 ratio between TMP and SDZ. With this ratio, the MICs of these drugs in combination decreased 5.0 and 5.4 times compared to the individual MICs for TMP and SDZ, respectively.…”

Determination of Sulfadiazine and N4-Acetylsulfadiazine in Biological Fluids by Liquid Chromatography on Silica Gel with an Aqueous Buffer as Mobile Phase

“…is affected by the presence of an organic solvent in the injected sample. A comparison of peak heights of sulfadiazine (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) pglml) obtained from plasma samples after protein precipitation by the adopted method and from pure buffer samples, respectively, indicated that the absolute recovery from pooled plasma samples is -76%. A similar comparison of peak height ratios of sulfadiazine and sulfamerazine, the internal standard, gave congruent standard curves (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) pg/ml) from pure mobile phase and plasma, respectively, showing that the recovery of sulfamerazine from plasma is of the same magnitude as for sulfadiazine.…”