Evaluation of antimicrobial interactions between chlorhexidine, quaternary ammonium compounds, preservatives and excipients

The antimicrobial interactions of 49 combinations of chlorhexidine, quaternary ammonium compounds, preservatives and excipients were evaluated by the method of Berenbaum and the checkerboard titration method, with Staphylococcus aureus CIP 53154 and Escherichia coli CIP 54127 as test strains. MIC determinations were carried out as a preliminary step, and relative growth intensity was used to describe the bacteriostatic activity of surface-active agents (Amonyl 380 BA, Amonyl 671 SB). In the study of combinations, results were interpreted with Fractional Inhibitory Concentration indexes and represented by isobolograms. A fair correlation was shown between the method of Berenbaum and the checkerboard titration method. Combinations between chlorhexidine, cetrimonium bromide and benzalkonium chloride were synergistic or additive; combinations of antiseptics and preservatives were generally not antagonistic. The methods were also well adapted to the study of interactions involving surface-active agents, a critical problem in the formulation of topical antimicrobial agents.