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APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method.

Abstract

APX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one used the EUCAST method. Here, we investigated the in vitro activity of APX001A and five comparators against 540 candidemia and 122 C. auris isolates. Isolates (17 Candida and 3 yeast species) were identified using CHROMagar, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and, when needed, internal transcribed space (ITS) sequencing. EUCAST E.Def 7.3.1 susceptibility testing included APX001A, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole. Wild-type upper limits (WT-UL) were established following the EUCAST principles for epidemiological cutoff value setting for APX001A, allowing classification as wild type (WT) or non-WT. APX001A MIC50 values (mg/liter) were as follows: Candida albicans, Candida dubliniensis, and Candida tropicalis, 0.004 to 0.008; Candida parapsilosis and Candida auris, 0.016; Candida glabrata, 0.06; and Candida krusei, >0.5. APX001A MICs against the rare species varied from ≤0.0005 (C. pelliculosa) to >0.5 (Candida norvegensis). APX001A was equally or more active in vitro than the comparators against all species except C. krusei and C. norvegensis Four isolates were APX001A non-WT; all were fluconazole resistant. A correlation was observed between APX001A and fluconazole MICs across all species except Candida guilliermondii and C. auris, and when comparing high and low fluconazole MIC isolates of C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, and C. auris APX001A showed promising in vitro activity against most Candida and other yeast species, including C. auris, compared to five comparators. WT-UL were suggested for the common species, and a new and unexplained correlation to fluconazole susceptibility was observed.

Authors+Show Affiliations

Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark maca@ssi.dk. Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark.Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30104264

Citation

Arendrup, Maiken Cavling, et al. "APX001A in Vitro Activity Against Contemporary Blood Isolates and Candida Auris Determined By the EUCAST Reference Method." Antimicrobial Agents and Chemotherapy, vol. 62, no. 10, 2018.
Arendrup MC, Chowdhary A, Astvad KMT, et al. APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method. Antimicrob Agents Chemother. 2018;62(10).
Arendrup, M. C., Chowdhary, A., Astvad, K. M. T., & Jørgensen, K. M. (2018). APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method. Antimicrobial Agents and Chemotherapy, 62(10), doi:10.1128/AAC.01225-18.
Arendrup MC, et al. APX001A in Vitro Activity Against Contemporary Blood Isolates and Candida Auris Determined By the EUCAST Reference Method. Antimicrob Agents Chemother. 2018;62(10) PubMed PMID: 30104264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method. AU - Arendrup,Maiken Cavling, AU - Chowdhary,Anuradha, AU - Astvad,Karen M T, AU - Jørgensen,Karin Meinike, Y1 - 2018/09/24/ PY - 2018/06/08/received PY - 2018/08/05/accepted PY - 2018/8/15/pubmed PY - 2019/10/1/medline PY - 2018/8/15/entrez KW - APX001A KW - Aspergillus KW - Candida KW - Candida auris KW - EUCAST KW - amphotericin B KW - antifungal susceptibility testing KW - azoles KW - candidemia KW - echinocandins JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 62 IS - 10 N2 - APX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one used the EUCAST method. Here, we investigated the in vitro activity of APX001A and five comparators against 540 candidemia and 122 C. auris isolates. Isolates (17 Candida and 3 yeast species) were identified using CHROMagar, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and, when needed, internal transcribed space (ITS) sequencing. EUCAST E.Def 7.3.1 susceptibility testing included APX001A, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole. Wild-type upper limits (WT-UL) were established following the EUCAST principles for epidemiological cutoff value setting for APX001A, allowing classification as wild type (WT) or non-WT. APX001A MIC50 values (mg/liter) were as follows: Candida albicans, Candida dubliniensis, and Candida tropicalis, 0.004 to 0.008; Candida parapsilosis and Candida auris, 0.016; Candida glabrata, 0.06; and Candida krusei, >0.5. APX001A MICs against the rare species varied from ≤0.0005 (C. pelliculosa) to >0.5 (Candida norvegensis). APX001A was equally or more active in vitro than the comparators against all species except C. krusei and C. norvegensis Four isolates were APX001A non-WT; all were fluconazole resistant. A correlation was observed between APX001A and fluconazole MICs across all species except Candida guilliermondii and C. auris, and when comparing high and low fluconazole MIC isolates of C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, and C. auris APX001A showed promising in vitro activity against most Candida and other yeast species, including C. auris, compared to five comparators. WT-UL were suggested for the common species, and a new and unexplained correlation to fluconazole susceptibility was observed. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/30104264/APX001A_In_Vitro_Activity_against_Contemporary_Blood_Isolates_and_Candida_auris_Determined_by_the_EUCAST_Reference_Method_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=30104264 DB - PRIME DP - Unbound Medicine ER -