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Effectiveness of fluconazole in murine Candida albicans and bacterial C. albicans peritonitis and abscess formation
R G Sawyer1, R B Adams, L K Rosenlof
1University of Michigan Department of Surgery, Ann Arbor, USA.
Abstract:
The role of fluconazole in the treatment of many forms of focal mycoses remains unclear. We studied the effectiveness of three different oral doses of fluconazole in three murine models of Candida albicans peritonitis leading to intra-abdominal abscess formation. During monomicrobial Candida infection, fluconazole decreased mortality and the number of C. albicans cultured per abscess; prolonged treatment also eliminated Escherichia coli translocation. In mixed C. albicans/E. coli/Bacteroides fragilis infection, prolonged treatment with higher doses of fluconazole decreased mortality, the number of abscesses formed, and the number C. albicans per abscess. In animals with a similar polymicrobial infection but with concurrent cefoxitin treatment, fluconazole decreased mortality and the number of C. albicans per abscess; in addition, prolonged treatment reduced the number of abscesses. Amphotericin B gave similar results in all three models. These data indicate that the clinical use of fluconazole in peritonitis should be investigated.
Insights
Fluconazole effectively reduced mortality and fungal burden in murine models of Candida peritonitis. Further clinical investigation is warranted for its use in treating abdominal abscesses.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- The efficacy of fluconazole for focal mycoses, particularly intra-abdominal abscesses caused by Candida albicans, requires further elucidation.
- Peritonitis involving polymicrobial infections presents complex treatment challenges.
Purpose of the Study:
- To evaluate the effectiveness of varying oral doses of fluconazole in murine models of Candida albicans peritonitis.
- To assess fluconazole's impact on mortality, fungal load, and abscess formation in both monomicrobial and polymicrobial infections.
Main Methods:
- Three distinct murine models of Candida albicans peritonitis were established, leading to intra-abdominal abscesses.
- Different oral doses and durations of fluconazole treatment were administered.
- Outcomes measured included mortality, Candida albicans burden per abscess, abscess formation, and bacterial translocation.
Main Results:
- Fluconazole treatment decreased mortality and Candida albicans counts in monomicrobial peritonitis models.
- Prolonged, higher-dose fluconazole regimens reduced mortality, abscesses, and fungal burden in polymicrobial infections.
- Concurrent cefoxitin treatment with fluconazole also showed benefits in polymicrobial settings.
- Amphotericin B demonstrated comparable efficacy across all models.
Conclusions:
- Fluconazole demonstrates significant therapeutic potential in murine models of Candida peritonitis and associated intra-abdominal abscesses.
- The findings support further clinical investigation into the use of fluconazole for peritonitis treatment.
- Dosing and treatment duration may be critical factors for optimizing fluconazole's effectiveness.