title: Therapies against murine Candida guilliermondii infection, relationship between in vitro antifungal pharmacodynamics and outcome.
abstract: BACKGROUND
  Candida guilliermondii has been recognized as an emerging pathogen showing a decreased susceptibility to fluconazole and considerably high echinocandin MICs.
  
  
  OBJECTIVE
  Evaluate the in vitro activity of anidulafungin in comparison to amphotericin B and fluconazole against different isolates of C. guilliermondii, and their efficacy in an immunosuppressed murine model of disseminated infection.
  
  
  METHODS
  The in vitro susceptibility of four strains against amphotericin B, fluconazole and anidulafungin was performed by using a reference broth microdilution method and time-kill curves. The in vivo efficacy was evaluated by determination of fungal load reduction in kidneys of infected animals receiving deoxycholate AMB at 0,8 mg/kg i.v., liposomal amphotericin B at 10 mg/kg i.v., fluconazole at 50 mg/kg, or anidulafungin at 10 mg/kg.
  
  
  RESULTS
  Amphotericin B and anidulafungin showed fungicidal activity, while fluconazole was fungistatic for all the strains. In the murine model, liposomal amphotericin B at 10 mg/kg/day was effective in reducing the tissue burden in kidneys of mice infected with any of the tested strains. However, amphotericin B, anidulafungin and fluconazole were only effective against those strains showing low MIC values.
  
  
  CONCLUSIONS
  Liposomal amphotericin B showed the higher activity and efficacy against the two strains of C. guilliermondii, in contrast to the poor effect of fluconazole and anidulafungin. Further studies with more isolates of C. guilliermondii representing a wider range of MICs should be carried out to assess whether there is any relationship between MIC values and anidulafungin efficacy.
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Katihuska
authors.initials: K
authors.lastname: Paredes
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Pastor
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain. Electronic address: javier.capilla@urv.cat.
authors.forename: Javier
authors.initials: J
authors.lastname: Capilla
authors.affiliation: Fungus Testing Laboratory, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Sutton
authors.affiliation: Unitat de Anatomia Patològica, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Mayayo
authors.affiliation: Fungus Testing Laboratory, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Annette W
authors.initials: AW
authors.lastname: Fothergill
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Guarro
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D021821:Communicable Diseases, Emerging / Q000382:microbiology; D004353:Drug Evaluation, Preclinical; D054714:Echinocandins / Q000494:pharmacology*; D015725:Fluconazole / Q000494:pharmacology*; D007668:Kidney / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000150:complications; D011897:Random Allocation; D013045:Species Specificity
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; C068538:liposomal amphotericin B; D000666:Amphotericin B; D015725:Fluconazole; D000077612:Anidulafungin
keywords: Animal model; Candida guilliermondii; Fungal infection; Infección fúngica; Modelo animal