The fungi of the order Onygenales can cause important human infections; however, their taxonomy and worldwide occurrence is still little known. We have studied and identified a representative number of clinical fungi belonging to that order from a reference laboratory in the USA. A total of 22 strains isolated from respiratory tract (40%) and human skin and nails (27.
View Article and Find Full Text PDFCyp51 contribution to azole resistance has been broadly studied and characterized in , whereas it remains poorly investigated in other clinically relevant species of the genus, such as those of section In this work, we aimed to analyze the impact of genes ( and ) on the voriconazole (VRC) response and resistance of and We generated CRISPR-Cas9 and knock-out mutants from strains with different genetic backgrounds and diverse patterns of azole susceptibility. Single gene deletions of genes resulted in 2 to 16-fold decrease of the VRC Minimum Inhibitory Concentration (MIC) values, which were below the VRC Epidemiological Cutoff Value (ECV) established by the Clinical and Laboratory Standards Institute (CLSI) irrespective of their parental strains susceptibilities. Gene expression studies in the tested species confirmed that participates more actively than in the transcriptional response of azole stress.
View Article and Find Full Text PDFThe genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
September 2020
Voriconazole (VCZ) is currently the first-line treatment for invasive aspergillosis, although the doses are limited by its poor solubility and high hepatic toxicity. The aim of this study was to develop a solid self-dispersing micellar system of VCZ to improve the pharmacokinetic/pharmacodynamic (PK/PD) relationship and reduce hepatotoxicity. In this work, solid micellar systems of VCZ are formulated with different polysorbate 80 ratios using mannitol as a hydrophilic carrier.
View Article and Find Full Text PDFInt J Antimicrob Agents
January 2020
Aspergillus fumigatus is the main causal agent of invasive aspergillosis (IA), however other species of the genus can also cause IA, such as Aspergillus flavus, Aspergillus terreus, Aspergillus niger and related cryptic species. This infectious disease mainly affects immunosuppressed patients and is linked to elevated mortality rates. As voriconazole is the treatment of choice for this condition, the relevant increase in the number of azole-resistant isolates in recent years has gathered alarming attention, as it also translates into an increase in clinical failures.
View Article and Find Full Text PDFInvasive pulmonary aspergillosis represents one of the most serious fungal infections among immunocompromised patients. In this study, we aimed to analyze the in vivo efficacy of prophylactic oral amphotericin B (AMB) encapsulated in modified chitosan-nanoparticles (Nanomerics' Molecular Envelope Technology (MET)) supplemented with a standardized extract of cultured mycelia (AHCC) in a murine model of pulmonary aspergillosis. We determined fungal burden and survival of mice and additionally, we carried out a cytokine analysis in an attempt to understand the immunomodulation of the extract.
View Article and Find Full Text PDFScopulariopsis is a common fungus in the environment, characterized by its intrinsic resistance to the available antifungal drugs. Around 70 cases of infection by this fungus have been described in the literature. Pulmonary and disseminated infections are the most common and their treatment is difficult; therefore, very diverse approaches have been taken, with varied results.
View Article and Find Full Text PDFAntimicrob Agents Chemother
July 2019
Invasive aspergillosis (IA) is a severe condition mainly caused by , although other species of the genus, such as section members, can also be involved. Voriconazole (VRC) is the recommended treatment for IA; however, the prevalence of azole-resistant isolates has alarmingly increased in recent years, and the underlying resistance mechanisms in non- species remain unclear. We have determined the susceptibility of 36 strains from section to VRC, posaconazole (POS), and itraconazole (ITC), and we have explored the role of Cyp51A and Cyp51B, both targets of azoles, in azole resistance.
View Article and Find Full Text PDFBackground: The incidence of systemic infections by Saccharomyces cerevisiae has increased in recent years, especially among immunocompromised patients. Amphotericin B, voriconazole or echinocandins have been used with favorable outcome against systemic infections by this fungus. However, clinical experience is limited and no in vivo studies have been conducted.
View Article and Find Full Text PDFAn experimental micellar formulation of 1:1.5 amphotericin B-sodium deoxycholate (AMB:DCH 1:1.5) was obtained and characterized to determine its aggregation state and particle size.
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