The joint in vitro action of polymyxin B and miconazole against pathogens associated with canine otitis externa from three European countries

Background: Canine otitis externa, an inflammation of the external ear canal, can be maintained and worsened by bacterial or fungal infections. For topical treatment, combinations of anti-inflammatory and antimicrobial ingredients are mainly used.

Hypothesis/objectives: This study was conducted to elucidate the in vitro activity of polymyxin B and miconazole against clinical bacterial isolates from three European countries, to investigate possible differences in sensitivity and to assess drug interactions.

Animals: Seventeen strains of Escherichia coli, 24 strains of Pseudomonas aeruginosa, 24 strains of Proteus mirabilis and 25 strains of Staphylococcus pseudintermedius from dogs with diagnosed otitis externa had been isolated in Germany, France and Italy.

Methods: Drug activities were evaluated by minimal inhibitory concentration (MIC) and minimal bactericidal concentration. The potentiation of polymyxin B plus miconazole was calculated using the fractional inhibitory concentration index (FICI). An FICI ≤0.5 defined synergy. Furthermore, geographical variations in the FICI and MIC were assessed by statistical analysis.

Results: Bacterial susceptibilities were comparable in different European countries, because there were no significant MIC and FICI variations (P > 0.05). As a single agent, polymyxin B had bactericidal activity against most E. coli and P. aeruginosa strains and, in higher concentrations, against S. pseudintermedius strains. Miconazole was bactericidal against all Staphylococcus strains. Synergy was demonstrated against strains of E. coli and P. aeruginosa (FICI = 0.25 and 0.50, respectively), whereas overall there was no interaction against S. pseudintermedius strains (FICI = 1.25). Proteus mirabilis strains were not inhibited by each of the drugs individually or by their combination.

Conclusions and clinical importance: In vitro synergy of polymyxin B and miconazole against E. coli and P. aeruginosa isolates indicates a rationale for applying both agents in combination to treat otitis externa when infected with these types of bacteria.