In Vivo Efficacy of Amphotericin B against Four Candida auris Clades

被引:5
作者
Forgacs, Lajos [1 ,2 ]
Borman, Andrew M. [3 ,4 ]
Kovacs, Renato [1 ,5 ]
Balazsi, David [1 ,2 ]
Toth, Zoltan [1 ,2 ]
Balazs, Bence [1 ,2 ]
Chiu Chun-Ju [1 ]
Kardos, Gabor [6 ]
Kovacs, Ilona [7 ]
Majoros, Laszlo [1 ]
机构
[1] Univ Debrecen, Fac Med, Dept Med Microbiol, Nagyerdei Krt 98, H-4032 Debrecen, Hungary
[2] Univ Debrecen, Doctoral Sch Pharmaceut Sci, Nagyerdei Krt 98, H-4032 Debrecen, Hungary
[3] Southmead Hosp, UK Natl Mycol Reference Lab, UK Hlth Secur Agcy, Bristol BS10 5NB, Avon, England
[4] Univ Exeter, Med Res Council Ctr Med Mycol MRC CMM, Exeter EX4 4QD, Devon, England
[5] Univ Debrecen, Fac Pharm, Nagyerdei Krt 98, H-4032 Debrecen, Hungary
[6] Univ Debrecen, Dept Metagen, Nagyerdei Krt 98, H-4032 Debrecen, Hungary
[7] Univ Debrecen, Kenezy Gyula Hosp, Dept Pathol, Nagyerdei Krt 98, H-4032 Debrecen, Hungary
关键词
Candida auris; amphotericin B; mouse; histopathology; in vivo; INFECTION; MICE;
D O I
10.3390/jof8050499
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p < 0.01), kidneys (p < 0.01) and brain (p < 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system.
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页数:16
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