Therapies against murine Candida guilliermondii infection, relationship between in vitro antifungal pharmacodynamics and outcome

• Published in: Revista iberoamericana de micologia Vol. 32; no. 1; pp. 34 - 39
• Main Authors: Paredes, Katihuska, Pastor, Francisco Javier, Capilla, Javier, Sutton, Deanna A, Mayayo, Emilio, Fothergill, Annette W, Guarro, Josep
• Format: Journal Article
• Language: English
• Published: Spain Elsevier Espana 01-01-2015
• Subjects: Amphotericin B - pharmacology; Animal model; Animals; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Candida - drug effects; Candida - isolation & purification; Candida guilliermondii; Candidiasis, Invasive - drug therapy; Candidiasis, Invasive - etiology; Candidiasis, Invasive - microbiology; Communicable Diseases, Emerging - microbiology; Drug Evaluation, Preclinical; Echinocandins - pharmacology; Fluconazole - pharmacology; Fungal infection; Infección fúngica; Infectious Disease; Kidney - microbiology; Male; Mice; Microbial Sensitivity Tests; Modelo animal; Neutropenia - complications; Random Allocation; Species Specificity; Candida guilliermondii; Animal model; Modelo animal; Infección fúngica; Fungal infection
• ISSN: 1130-1406; 2173-9188
• DOI: 10.1016/j.riam.2013.10.008

Abstract Background Candida guilliermondii has been recognized as an emerging pathogen showing a decreased susceptibility to fluconazole and considerably high echinocandin MICs. Aims 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.