Investigation of synergism between combinations of ciprofloxacin, polymyxin, sulphadiazine and p-aminobenzoic acid.

Subinhibitory concentrations of combinations of any two of ciprofloxacin, colistin (or polymyxin B), sodium sulphadiazine and p-aminobenzoic acid were shown by checkerboard minimum inhibitory concentration determinations to have synergistic inhibitory activity against Pseudomonas aeruginosa and to have either synergistic or additive activity against Staphylococcus aureus. In addition, sulphadiazine plus either ciprofloxacin or polymyxin showed markedly enhanced killing activity against both P. aeruginosa and S. aureus. p-Aminobenzoic acid plus either ciprofloxacin or polymyxin also demonstrated enhanced killing activity against P. aeruginosa but these combinations were less effective in enhancing activity against S. aureus. Ciprofloxacin in combination with polymyxin had a marked synergistic effect against P. aeruginosa but only a slight synergistic effect against S. aureus. These findings indicate a potential usefulness for the synergistic combinations against P. aeruginosa and S. aureus in the clinical situation; that is, they indicate an extended role for sulphonamides and support a potential role for p-aminobenzoic acid as enhancers of the activity of primary antibacterial agents such as ciprofloxacin and polymyxin. We suggest that for a second antibacterial to enhance the activity of ciprofloxacin, it may be necessary for the second antibacterial to increase cell permeability so increasing bacterial uptake of ciprofloxacin.