title: Interaction between saquinavir and antimycotic drugs on C. albicans and C. neoformans strains.
abstract: Candidiasis and cryptococcosis are the most common fungal diseases among patients suffering from HIV infection. In the present work we assess whether the combined therapies, proteinase inhibitors and antimycotic drugs, could modify the therapeutic effect of antimycotics. An in vitro study to evaluate the antifungal effect of saquinavir and antimycotic drugs combination on yeast growth was performed. Strains of C. albicans and C. neoformans from HIV-seropositive patients were used. Susceptibility tests of yeasts to amphotericin B, 5-fluorocytosine, miconazole and fluconazole, singly and in combination with saquinavir, were performed in two different media. In the combinations the antimycotic agents and saquinavir were tested at sub-inhibitory concentrations: 0.1-10 microg ml(-1) and 12.50 microg ml(-1), respectively. The fractionary inhibitory concentration (FIC) index was also calculated. The results show that the interaction between saquinavir and all the antimycotic drugs never resulted in antagonism. Fluconazole acts in more synergistic way, no matter which medium is used. The combined therapy miconazole/saquinavir results in synergism, especially in Sabouraud. The total absence of antagonism and the presence of synergism suggest that a combined therapy could be proposed in the treatment of HIV-seropositive patients to reduce side effects, thanks to the use of lower doses of antimycotic drugs.
authors.affiliation: Department of Medicine Laboratory, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Casolari
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rossi
authors.forename: Giosué
authors.initials: G
authors.lastname: Baggio
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppi
authors.forename: Ginevra
authors.initials: G
authors.lastname: Zandomeneghi
authors.forename: Antonio Ippazio
authors.initials: AI
authors.lastname: Ruberto
authors.forename: Claudio
authors.initials: C
authors.lastname: Farina
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fabio
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanca
authors.forename: Mario
authors.initials: M
authors.lastname: Castelli
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D019258:Saquinavir / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D019258:Saquinavir