title: 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.
authors.affiliation: Charité - Universitätsmedizin Berlin, Klinik für Anästhesiologie und operative Intensivmedizin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pietschmann
authors.forename: Katrin
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Michael
authors.initials: M
authors.lastname: Voget
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pison
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D003470:Culture Media; D004338:Drug Combinations; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D005434:Flow Cytometry / Q000662:veterinary; D008290:Malassezia / Q000187:drug effects*; D008825:Miconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D008856:Microscopy, Fluorescence / Q000662:veterinary; D011112:Polymyxin B / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D057789:Staphylococcus intermedius / Q000187:drug effects; D014508:Urea / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003470:Culture Media; D004338:Drug Combinations; D008825:Miconazole; D014508:Urea; D011112:Polymyxin B