title: Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro.
abstract: Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1μgmL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4μgmL(-1)and from 0.0625 to 1μgmL(-1) for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125μgmL(-1) and from 0.0039 to 0.0312μgmL(-1) for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p<0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum.
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Postgraduate Program in Medical Sciences, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil. Electronic address: brilhante@ufc.br.
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Érica Pacheco
authors.initials: ÉP
authors.lastname: Caetano
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Giovanna Barbosa
authors.initials: GB
authors.lastname: Riello
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Glaucia Morgana de Melo
authors.initials: GM
authors.lastname: Guedes
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Postgraduate Program in Medical Sciences, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Débora de Souza Collares Maia
authors.initials: Dde S
authors.lastname: Castelo-Branco
authors.affiliation: Postgraduate Program in Medical Sciences, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Maria Auxiliadora Bezerra
authors.initials: MA
authors.lastname: Fechine
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Jonathas Sales de
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Zoilo Pires de
authors.initials: ZP
authors.lastname: Camargo
authors.affiliation: Hospital São José, Fortaleza, CE, Brazil.
authors.forename: Jacó Ricarte Lima de
authors.initials: JR
authors.lastname: Mesquita
authors.affiliation: Department of Statistics and Applied Mathematics, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: André Jalles
authors.initials: AJ
authors.lastname: Monteiro
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Postgraduate Program in Medical Sciences, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Rossana de Aguiar
authors.initials: Rde A
authors.lastname: Cordeiro
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Postgraduate Program in Veterinary Sciences, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Postgraduate Program in Medical Sciences, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D004357:Drug Synergism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006658:Histoplasma / Q000187:drug effects*; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D019438:Ritonavir / Q000494:pharmacology*; D019258:Saquinavir / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D017320:HIV Protease Inhibitors; D017964:Itraconazole; D019258:Saquinavir; D019438:Ritonavir
keywords: Histoplasma capsulatum; Itraconazole; Ritonavir; Saquinavir