Comparison of In Vitro Killing Activity of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in RPMI-1640 in the Absence and Presence of Human Serum

Microorganisms

卷:9

JeffreyB. Locke¹  Lajos Forgács²  Fruzsina Nagy²  Gábor Kardos²  Zoltán Tóth²  Renátó Kovács²  László Majoros²  AndrewM. Borman³ 

[1] Cidara Therapeutics, Inc., 6310 Nancy Ridge Drive, Suite 101, San Diego, CA 92121, USA;

[2] Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary;

[3] UK National Mycology Reference Laboratory, Public Health England, Science Quarter, Southmead Hospital, Bristol BS10 5NB, UK;

关键词: Candida auris;    rezafungin;    echinocandin;    killing rate;    time kill;    serum;   

DOI  :  10.3390/microorganisms9040863

来源: DOAJ

【 摘 要 】

Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1-≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1-≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades.

【 授权许可】

Unknown