Enhancement of antibacterial activity by p-aminobenzoic acid and sulphadiazine

Investigation of Synergism between Combinations of Ciprofloxacin, Polymyxin, Sulphadiazine and p-Aminobenzoic acid

“…2). These results are similar to those obtained previously with a combination of sulphonamide and penicillin, which did not show a marked effect on killing times against cell suspensions, but produced markedly increased inhibitory activity against cultures in nutrient +sodium sulphadiazine (7.0 p g mL-'+750 pg mL-1 7 ), 0 colismedia (Bigger 1944;Weinstein et a1 1964;Richards & Xing 1992b). The synergistic inhibitory effect observed with combinations of sulphadiazine plus either ciprofloxacin or polymyxin (colistin) in Isosensitest broth (Figs 1, 2, Table 1) may be explained in terms of the sulphadiazine modifying cell envelope permeability (Richards et a1 1991a) and thereby facilitating uptake of ciprofloxacin and polymyxin.…”

Separation and Quantification of Murein and Precursors from Enterobacter cloacae after Treatment with Trimethoprim and Sulphadiazine

“…The results presented here in conjunction with previously reported results , 1992Richards et a1 1991Richards et a1 , 1993a indicate that the enhanced activity of trimethoprim plus sulphadiazine against E. cloacae is due to an additional effect on the inhibition of the bacterial peptidoglycan biosynthesis (possibly an inhibition of the transglycosylation step), which leads to changes of cell morphology and resultant change in bacterial cell permeability. This additional effect is considered to be a fundamental part of the antibacterial action of these antimetabolites.…”

“…The results suggest that the enhanced activity of trimethoprim plus sulphadiazine against E. cloacae is caused by an additional effect on the inhibition of the bacterial peptidoglycan biosynthesis and that this additional effect is a fundamental part of the antibacterial action of the antimetabolites. This effect leads to changes of cell morphology and resultant changes in bacterial cell permeability.Recent work has indicated that the enhanced activity of combinations of trimethoprim and sulphonamides at subinhibitory concentrations is related to mutually increased uptakes of both antibacterials, even when the bacteria are resistant to one member of the combination , 1992Richards et al , 1993a. It has been proposed that the sequential blockade of folinic acid synthesis imposed by trimethoprim plus a sulphonamide results in changes to the bacterial cell permeability barrier which, in turn, leads to increased bacterial uptake of both antibacterial agents , 1992Richards et al , 1993a.…”

“…This effect leads to changes of cell morphology and resultant changes in bacterial cell permeability.Recent work has indicated that the enhanced activity of combinations of trimethoprim and sulphonamides at subinhibitory concentrations is related to mutually increased uptakes of both antibacterials, even when the bacteria are resistant to one member of the combination , 1992Richards et al , 1993a. It has been proposed that the sequential blockade of folinic acid synthesis imposed by trimethoprim plus a sulphonamide results in changes to the bacterial cell permeability barrier which, in turn, leads to increased bacterial uptake of both antibacterial agents , 1992Richards et al , 1993a. Electron microscopy indicated that the morphological changes produced by the action of trimethoprim and sulphadiazine on Enterobacter cloacae (Richards et al 1993a) and Enterococcus faecalis (unpublished results) involved damage to the peptidoglycan of each organism and had an effect on septum completion in E. faecalis.…”

“…Recent work has indicated that the enhanced activity of combinations of trimethoprim and sulphonamides at subinhibitory concentrations is related to mutually increased uptakes of both antibacterials, even when the bacteria are resistant to one member of the combination , 1992Richards et al , 1993a. It has been proposed that the sequential blockade of folinic acid synthesis imposed by trimethoprim plus a sulphonamide results in changes to the bacterial cell permeability barrier which, in turn, leads to increased bacterial uptake of both antibacterial agents , 1992Richards et al , 1993a.…”