title: Isobolographic analysis of pharmacodynamic interactions between antifungal agents and ciprofloxacin against Candida albicans and Aspergillus fumigatus.
abstract: Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 microg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis.
authors.affiliation: Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Theodouli
authors.initials: T
authors.lastname: Stergiopoulou
authors.forename: Joseph
authors.initials: J
authors.lastname: Meletiadis
authors.forename: Tin
authors.initials: T
authors.lastname: Sein
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Papaioannidou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Tsiouris
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002939:Ciprofloxacin / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D012044:Regression Analysis
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002939:Ciprofloxacin