In Vitro Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC Determination.

Antimicrobial Agents and Chemotherapy
Karin Meinike JørgensenMaiken Cavling Arendrup

Abstract

Manogepix (APX001A) is the active moiety of the drug candidate fosmanogepix (APX001), currently in clinical development for the treatment of invasive fungal infections. We compared manogepix EUCAST minimum effective concentrations (MECs) to MICs of five comparators and CLSI MECs and MICs by a colorimetric method against contemporary molds. EUCAST susceptibility testing was performed for 161 isolates. Interlaboratory and intermethod reproducibility were determined by comparison with published manogepix MECs. Colorimetric MICs (measuring metabolic activity) were evaluated using three Aspergillus fumigatus isolates and one Aspergillus flavus isolate with four inocula at 24 to 48 h of incubation and 1 to 3 h 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT)/menadione (MEN) exposure. Manogepix modal MECs (range in mg/liter) against Aspergillus species were 0.03 to 0.06 (0.008 to 0.125) and unaffected by itraconazole resistance. Manogepix was as active against two Fusarium isolates but inactive against Trichophyton interdigitale, Lichtheimia ramosa, and Rhizomucor pusillus isolates (MECs >0.5). Modal MEC/MICs were ≥3 2-fold dilutions apart without overlapping ranges comparing manogepix with amphoteri...Continue Reading

References

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Aug 15, 2018·Antimicrobial Agents and Chemotherapy·Maiken Cavling ArendrupKarin Meinike Jørgensen
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Citations

Jul 15, 2020·Antimicrobial Agents and Chemotherapy·Maiken Cavling ArendrupJoseph Meletiadis
Jun 3, 2021·Current Fungal Infection Reports·Garret T Seiler, Luis Ostrosky-Zeichner
Jul 8, 2021·Expert Opinion on Pharmacotherapy·Adam G Stewart, David L Paterson
Jul 27, 2021·Antimicrobial Agents and Chemotherapy·Shareef K ShaheenWilliam J Steinbach

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