fluconazole
Experimental TherapeuticsThe Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal InfectionInvasive fungal diseases represent an unmet clinical need that could benefit from novel immunotherapeutic approaches. Host pattern recognition receptors (e.g., Toll-like receptors, C-type lectins, or scavenger receptors) that sense conserved fungal cell wall constituents may provide suitable immunotherapeutic antifungal agents. Thus, we explored the therapeutic potential of the lymphocyte class I scavenger receptor CD5, a nonredundant...
Mechanisms of ResistanceExperimental Evolution Identifies Adaptive Aneuploidy as a Mechanism of Fluconazole Resistance in Candida aurisCandida auris is a newly emerging fungal pathogen of humans and has attracted considerable attention from both the clinical and basic research communities. Clinical isolates of C. auris are often resistant to one or more antifungal agents. To explore how antifungal resistance develops, we performed...
Mechanisms of ResistanceFirst Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and/or Y132F+K143R in TurkeyClonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of FLZR C. parapsilosis blood isolates have not been reported in...
SusceptibilityManogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICsFosmanogepix is a novel prodrug in a new class of antifungal agents. Manogepix is the active moiety. We evaluated the CLSI and EUCAST MICs of manogepix and eight comparators against Candida auris. CLSI M27-A3 susceptibility testing of manogepix was performed for 122 C. auris isolates and compared to...
SusceptibilityManogepix (APX001A) Displays Potent In Vitro Activity against Human Pathogenic Yeast, but with an Unexpected Correlation to Fluconazole MICsManogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here, we extended this study and included isolates with acquired fluconazole resistance. Isolates (n = 835) were identified using CHROMagar, matrix-assisted laser desorption ionization–time of...
Experimental TherapeuticsThe Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida aurisThe in vitro and in vivo activity of the arylamidine T-2307 against Candida auris was evaluated. T-2307 demonstrated in vitro activity (MIC ranges ≤ 0.008 to 0.015 μg/ml at 50% inhibition; 0.125 to >4 μg/ml at 100% inhibition).
PharmacologyPharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal MeningoencephalitisCryptococcus spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options are desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize the exposure-response relationship in a rabbit model of cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were...
SusceptibilityFluconazole Resistance in Isolates of Uncommon Pathogenic Yeast Species from the United KingdomThe triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasive Candida infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with...
Clinical TherapeuticsPopulation Pharmacokinetic Study of Prophylactic Fluconazole in Preterm Infants for Prevention of Invasive CandidiasisFluconazole is an antifungal agent with reported evidence for its prophylactic effect against systemic fungal infection in preterm infants. The aim of this study was to build a population pharmacokinetic model to evaluate the pharmacokinetic characteristics of intravenous and oral fluconazole in preterm infants with the current prophylactic fluconazole dosing regimen.
Mechanisms of ResistanceContribution of Clinically Derived Mutations in the Gene Encoding the Zinc Cluster Transcription Factor Mrr2 to Fluconazole Antifungal Resistance and CDR1 Expression in Candida albicansMutations in genes encoding zinc cluster transcription factors (ZCFs) such as TAC1, MRR1, and UPC2 play a key role in Candida albicans azole antifungal resistance. Artificial activation of the ZCF Mrr2 has shown increased expression of the gene encoding the Cdr1 efflux pump and resistance to fluconazole.