Aspergillus
Experimental TherapeuticsAntifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo ModelAspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro.
Experimental TherapeuticsEfficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis PneumoniaAntifungal prophylaxis is recommended to prevent invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive...
SusceptibilityOlorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum ActivityOlorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus. Here, we explored the MIC variability in more detail and prospectively investigated the susceptibility of contemporary clinical mold isolates...
Experimental TherapeuticsPreclinical Evaluation of Acylhydrazone SB-AF-1002 as a Novel Broad-Spectrum Antifungal AgentThe incidence of invasive fungal infections is rising due to the increase in susceptible populations. Current clinically available drugs have therapeutic limitations due to toxicity, a narrow spectrum of activity, and, more importantly, the consistent rise of fungal species that are intrinsically resistant or that develop resistance due to prolonged therapy. Thus, there is an urgent need for new broad-spectrum antifungal agents with low...
Editor's Pick Mechanisms of ResistanceA Novel Combination of CYP51A Mutations Confers Pan-Azole Resistance in Aspergillus fumigatusThe treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates, and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide. The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype...
Editor's Pick SusceptibilityIn Vitro Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC DeterminationManogepix (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...
SusceptibilityIn Vitro and In Vivo Study on the Synergistic Effect of Minocycline and Azoles against Pathogenic FungiIn vitro and in vivo interactions of minocycline and azoles, including itraconazole, voriconazole, and posaconazole, against filamentous pathogenic fungi were investigated. A total of 56 clinical isolates were studied in vitro via broth microdilution checkerboard technique, including 20 strains of Aspergillus fumigatus, 7 strains of...
Experimental TherapeuticsDerivatives of the Antimalarial Drug Mefloquine Are Broad-Spectrum Antifungal Molecules with Activity against Drug-Resistant Clinical IsolatesThe antifungal pharmacopeia is critically small, particularly in light of the recent emergence of multidrug-resistant pathogens, such as Candida auris. Here, we report that derivatives of the antimalarial drug mefloquine have broad-spectrum antifungal activity against pathogenic yeasts and molds.
Experimental TherapeuticsGalactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary AspergillosisGalactomannan (GM) detection in biological samples has been shown to predict therapeutic response by azoles and polyenes. In a murine invasive pulmonary aspergillosis model, fosmanogepix or posaconazole treatment resulted in an ∼6- to 7-log reduction in conidial equivalents (CE)/g lung tissue after 96 h versus placebo.
SusceptibilityNew Antifungal Susceptibility Test Based on Chitin Detection by Image CytometryThe antifungal susceptibility tests used in clinical laboratories have several limitations. We developed a new test, SensiFONG, based on the detection of chitin levels after exposure to antifungal drugs. The optimal culture conditions were 30°C for 6 h for yeast strains and 26°C for 16 h for molds. The strains were exposed to a range of echinocandin or azole concentrations. Chitin was stained with calcofluor white.