Does Candida Escape Antifungal Treatment in the Gallbladder?
Thomas Glück, MD
In vivo imaging using bioluminescent Candida in a mouse model demonstrated viable fungi in the gallbladder after systemic antifungal treatment.
Candida albicans is an important fungal pathogen that can cause life-threatening systemic infection. In some patients, candidemia persists despite appropriate antifungal treatment; the focus of infection often remains unclear in such cases. To investigate this phenomenon, researchers in Germany used a murine model and in vivo imaging with bioluminescent C. albicans, which allowed temporal and spatial observation of disease development in individual animals.
Twenty-four hours after the mice were infected intravenously with Candida, intensity of the fungal bioluminescent signal was greatest in the kidneys. Placebo-group animals quickly developed clinical symptoms of severe disease and had to be euthanized 56 to 72 hours postinfection. The fungal burden in the kidneys was approximately fivefold higher than the infection dose.
Mice that received caspofungin antifungal treatment from 8 hours postinfection through day 3, and fluconazole from day 4 through day 9, developed only mild disease symptoms, showed decreasing bioluminescence signal intensity in the kidneys, and cleared the fungi in the kidneys by the end of treatment. However, 48 hours postinfection, three of these eight animals developed a bioluminescence signal in the gallbladder that persisted until the end of the experiment. Postmortem microscopic examination of gallbladder contents showed long Candida filaments; plating yielded pure cultures of bioluminescent C. albicans. Some fecal pellets from mice showing a gallbladder signal also produced bioluminescence signals and contained viable fungi.
Further analysis demonstrated a marked loss of activity of all tested antifungals (echinocandins, amphotericin B, azoles) in the presence of bile. The presence of bile salts increased the minimum inhibitory concentrations of these agents by 10 to >1000.
Citation(s):
Jacobsen ID et al. In vivo imaging of disseminated murine Candida albicans infection reveals unexpected host sites of fungal persistence during antifungal therapy. J Antimicrob Chemother 2014 Jun 20; [e-pub ahead of print].
