Tissue Cytokine Levels and Histopathology Following Liposomal Amphotericin B (LA) or Caspofungin (C) Treatment of Echinocandin Resistant (ER) or Sensitive (ES) Candida glabrata (Cg) Infection

Ref ID: 19269

Author:

J. Olson, J. Schwartz, N. Nguyen, D. Hahka, J. Adler-Moore

Author address:

California State Polytechnic Univ., Pomona, CA; Charles River Labs, Davis, CA.

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Introduction: The incidence of candidiasis caused by non-Candida albicans species, along with increasing use of echinocandins has led to more Cg strains that are ER. In this study we compared efficacy, tissue cytokine levels and histopathology of ER and ES Cg infected mice following C or LA treatment alone or in combination. Methods: Mice (14/gp) were immunosuppressed with cyclophosphamide on d-2, 0, +2, +4, challenged iv with 5×106 (ER Cg) or 6×106 (ES Cg), and 24h later, treated (Tx) with 5 or 7.5mg/kg LA or 5mg/kg C (5C), alone (mono) or in combination (combo). On d+4, tissues (7/gp) were collected for CFU/g, multi-bead cytokine analysis, and histopathology staining with H&E for tissue pathology and Gridley’s for fungal detection. Results: ES Cg: CFU/g in all tissues were lower with all drug Txs vs D5W (P < 0.05); in the heart and kidneys, combo Txs produced lower CFU/g than mono Txs (P < 0.05). Histopathology results showed similar infection patterns. With combo Txs, TNFα , IL-6 and IL-12 were lower in heart and kidneys vs D5W (P < 0.05) and combo Txs gave lower IL-1α , IL-1β and IFNγ levels vs mono Txs (P < 0.05). With D5W, marked inflammation, degeneration and necrosis were seen in kidneys, heart and bladder but with combo Txs tissue damage was decreased in kidneys and heart. ER Cg: CFU/g in all tissues were lower with LA monos or combo Txs vs C or D5W (P <0.05). In the kidneys, C Tx gave lower IL-1α , IL-1β , IL-10 IL-12, INFγ levels vs LA monos, combos, or D5W (P = 0.05), but in the heart C Tx produced higher levels of IL- 1β , IL-10, TNFα than 5LA mono(P <0.05). Comparable inflammation, degeneration and necrosis was observed in the kidneys and bladder of D5W or C treated mice which were heavily infected with yeast; in comparison, there was minimal tissue pathology or evidence of yeast infection in mice given 7.5LA mono or combos Tx. Conclusion: Combo tx (LA + C) was better than either drug alone for the treatment of ES Cg infection based on decreased yeast burden, minimal tissue damage, and reduced proinflammatory cytokine levels. In comparison, using these same parameters, 7.5LA mono was as effective as combo therapy for treating ER Cg infection demonstrating that combo tx is not indicated for treating ER infections.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster