Synergistic effects of Miconazole and Polymyxin B on microbial pathogens

Abstract

The therapeutic value of antibiotics depends on the susceptibility of the infecting microorganism and the pharmacological profile of the drugs. To assess the value of an antibiotic combination of polymyxin B and miconazole this study examined the in vitro synergistic potential of the two drugs on Gram-negative and Gram-positive bacteria and yeast. Antifungal and antibacterial activity was tested by minimum inhibitory concentration (MIC) of broth macrodilution and urea broth microdilution, by fluorescence microscopy and flow cytometry. Synergism was calculated using the fractional inhibitory concentration index (FICi). With Staphylococcus intermedius as target we found up to an eightfold reduction of the individual MICs when both drugs were combined. However, the FICi was 0.63 suggesting no real interaction between the two drugs. With Escherichia coli, Pseudomonas aeruginosa, and Malassezia pachydermatis as targets the antimicrobial drug combination reduced the MICs of polymyxin B and miconazole from fourfold to hundredfold resulting in FICi between 0.06 and 0.5 which defines a synergistic action. Thus, if polymyxin B and miconazole are combined their effect is greater than the sum of the effects observed with polymyxin B and miconazole independently, revealing bactericidal and fungicidal synergism. Our results indicate a strong therapeutic value for the combination of these antimicrobial agents against Gram-negative bacteria and yeast and a weaker value against Gram positive bacteria for clinical situations where these pathogens are involved.

Evaluation of In Vitro Synergistic Interaction of Miconazole and Polymyxin B Against Clinical Strains of Malassezia pachydermatis

“…Regarding fungi, synergy of PMX and MCZ has also been demonstrated against Candida albicans [24] and M. pachydermatis. However, with reference to M. pachydermatis, data has only been collected for one strain, which was, furthermore, a reference strain coming from a fungal collection (M. pachydermatis CBS 1879) [12]. Our data confirm that a synergistic interaction of PMX and MCZ exists against field strains of M. pachydermatis.…”

“…Up until now, synergy between PMX and MCZ has been demonstrated against different bacterial species often involved in canine otitis externa, such as Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli [11,12], but in most cases experiments have been conducted on reference strains. Moreover, Pietschmann et al (2013) have recently shown an in vitro synergy of PMX and MCZ against field strains (i.e.…”

“…MCZ is known to inhibit the synthesis of ergosterol, a bioregulator of membrane integrity in fungal cells [21]. MCZ can also function in its antifungal role by inducing reactive oxygen species which results in fungal cell death [22,23].Up until now, synergy between PMX and MCZ has been demonstrated against different bacterial species often involved in canine otitis externa, such as Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli [11,12], but in most cases experiments have been conducted on reference strains. Moreover, Pietschmann et al (2013) have recently shown an in vitro synergy of PMX and MCZ against field strains (i.e.…”

“…Such a positive response stems from the fact that PMX is effective against a broad variety of Gram-negative and, to a lesser extent, Grampositive bacteria, as well as having antifungal properties [7,8] [9,10]. Moreover, a synergistic interaction in vitro between PMX and MCZ has been demonstrated against different species of bacteria frequently involved in canine otitis externa [11][12][13]. Synergy, in this context, can be defined as the increased effectiveness of multiple drugs that, in combination, are more efficient than the cumulative effects of the individual components [14].…”

“…Synergy, in this context, can be defined as the increased effectiveness of multiple drugs that, in combination, are more efficient than the cumulative effects of the individual components [14]. Regarding M. pachydermatis, synergy has so far only been demonstrated against one type strain (M. pachydermatis CBS 1879) [12]. The aim of the present study was to evaluate the in vitro antifungal activity of the combination of PMX and MCZ against clinical strains of M. pachydermatis associated with canine otitis externa.…”