In Vivo Efficacy of Amphotericin B Against Four Candida auris Clades
Absztrakt
Candida auris is an emerging multidrug resistance microbe with the potential to cause outbreaks in healthcare facilities. Although echinocandin is the first line treatment for the invasive candidiasis caused by C. auris, in certain situations (i.e. meningitis, urinary tract fungal infection, and treatment failure with echinocandin)the Amphotericin B (AMB) remain the drug of choice for the treatment. In this study, four isolates (C. auris 12372, 204, 196, and I-156 from East Asia (Japan), South Africa, South Asia, and South America (Israel) respectively) were tested for the response of AMB treatment on the neutropenic BALB/c mice model treated with cyclophosphamide to suppress the immune system before intravenous inoculation. In the lethality study, ten mice in each group were inoculated with C. auris with 107 CFU per mouse in the volume of 200 μL. Every infected mice was treated with AMB with 1 mg/kg dosing and for 5 days following infection. Only the East Asian isolate had significantly improved survival rate, all the mice in the other 3 isolates (South Africa, South Asia, and South America) died before day 21. Heart, brain and both kidneys were invaded by the fungal cells and can be seen both in the fungal tissue burden experiments and histopathological tissue sections. In the heart histopathological tissue sections, contraction band necrosis can be observed in the myocardium. Renal tubule damage and necrosis sparing the glomeruli were found in the kidney parenchyma samples. Our result showed the possible higher dose or combination of antifungal therapy would be needed to completely eradicate the fungal cells in the central nervous system and the heart.