title: Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
abstract: Ibuprofen, a non-steroidal anti-inflammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg/ml, ibuprofen showed a rapid cidal activity against exponential growth phase C. albicans, accompanied by rapid and extensive leakage of intracellular K+, permeation to propidium iodide, lysis of spheroplasts and severe membrane ultrastructural alterations. These results indicate that the killing of Candida cells is due to direct damage to the cytoplasmic membrane. At 5 mg/ml, ibuprofen inhibited growth; however, it did not kill the yeasts and did not directly affect the cytoplasmic membrane. Evaluation of yeast metabolic vitality with the fluorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. The combination of ibuprofen with fluconazole resulted in synergic activity with eight of the 12 Candida strains studied, including four of the five fluconazole-resistant strains. The MICs of fluconazole for the fluconazole-resistant strains decreased 2-128-fold when the drug was associated with ibuprofen. When in combination with fluconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the practicability of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties.
authors.affiliation: *Department of Microbiology, Porto School of Medicine, University of Porto, †Institute of Pathology and Molecular Immunology of Porto University, ‡Department of Gynaecology, Porto School of Medicine, University of Porto, Porto, Portugal and §Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden.
authors.forename: Cidália
authors.initials: C
authors.lastname: Pina-Vaz
authors.affiliation: *Department of Microbiology, Porto School of Medicine, University of Porto, †Institute of Pathology and Molecular Immunology of Porto University, ‡Department of Gynaecology, Porto School of Medicine, University of Porto, Porto, Portugal and §Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden.
authors.forename: Filipe
authors.initials: F
authors.lastname: Sansonetty
authors.affiliation: *Department of Microbiology, Porto School of Medicine, University of Porto, †Institute of Pathology and Molecular Immunology of Porto University, ‡Department of Gynaecology, Porto School of Medicine, University of Porto, Porto, Portugal and §Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden.
authors.forename: Acácio G
authors.initials: AG
authors.lastname: Rodrigues
authors.affiliation: *Department of Microbiology, Porto School of Medicine, University of Porto, †Institute of Pathology and Molecular Immunology of Porto University, ‡Department of Gynaecology, Porto School of Medicine, University of Porto, Porto, Portugal and §Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Martinez-DE-Oliveira
authors.affiliation: *Department of Microbiology, Porto School of Medicine, University of Porto, †Institute of Pathology and Molecular Immunology of Porto University, ‡Department of Gynaecology, Porto School of Medicine, University of Porto, Porto, Portugal and §Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden.
authors.forename: António F
authors.initials: AF
authors.lastname: Fonseca
authors.affiliation: *Department of Microbiology, Porto School of Medicine, University of Porto, †Institute of Pathology and Molecular Immunology of Porto University, ‡Department of Gynaecology, Porto School of Medicine, University of Porto, Porto, Portugal and §Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden.
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Mårdh
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole; D007052:Ibuprofen