Six anionic and five nonionic surfactants were tested for their effect on the fungistatic action of clotrimazole against Candida albicans. All of the anionic agents that did not contain an ethylene oxide group were capable of potentiating the anti-Candida activity of clotrimazole, whereas all five members of the polyoxyethylene surfactant group, including four nonionic agents and one anionic agent, acted in an antagonistic fashion. The combination of clotrimazole and the anionic surfactant dioctyl sodium sulfosuccinate was the most potent in synergy and, thus, more precise studies were made with this combination. Although appropriate combinations of the two drugs showed a potent fungicidal activity against proliferating cultures, none of these combinations tested was lethal when cell growth was restricted by nutritional deficiency. The lethal effect of the combined drugs was partly reversed when growing cultures were treated in the presence of an osmotic stabilizer. Whether cells were treated with moderate and higher concentrations of clotrimazole and dioctyl sodium sulfosuccinate, alone or in combination, there was little change in cell wall content of total protein, carbohydrate, or lipid from that in untreated control cells. However, there was a significant decrease in the cell wall content of phospholipid when moderate concentrations of the two drugs were combined.An anionic surfactant, dioctyl sodium sulfosuccinate (DSS), is mainly used as a wetting agent in industrial, pharmaceutical, cosmetic, and food applications and as an ingredient in some laxatives. This surfactant has also been known to have bactericidal action against various bacteria, in particular, gram-positive bacteria, and has been used as a topical antiseptic.We have previously reported that DSS exhibits a limited antifungal activity against Candida albicans and several other yeasts, whereas in combination with the imidazole antimycotic clotrimazole, it shows effective, synergistic fungicidal action (8,19).In the present study, we first attempted to examine the effect of various other surfactants, both anionic and nonionic, used in combination with clotrimazole on the viability ofC. albicans cultures. Although several anionic surfactants were also found to be synergistic, none of them was as potent as DSS. Since many in vitro studies on the evaluation of the antifungal activity of clotrimazole revealed that this drug is basically fungistatic rather than fungicidal at clinically attainable concentrations in tissues (7,13,16,17), appropriate combinations of clotrimazole with DSS may provide a formulation for more effective preparations of this antimycotic.The potential usefulness of the combined drugs for therapy of human mycoses prompted us to investigate further the mechanism of their synergistic action. In this study, we have characterized several factors that are involved in the in vitro antifungal activity of DSS plus clotrimazole against C. albicans. In addition, experiments were also carried out to examine changes in the chemical composi...
