Molecular basis of antifungal drug resistance in yeasts.

Besides inherent differences in in vitro susceptibilities, clinically-relevant yeast species may acquire resistance upon exposure to most antifungal drugs used in the clinic. In recent years, major fundamental research studies have been conducted to improve our understanding of the molecular basis of antifungal resistance. This topic is of major interest as antifungal resistance in yeast is clearly evolving and is correlated with clinical failure.

Resistance in human pathogenic yeasts and filamentous fungi: prevalence, underlying molecular mechanisms and link to the use of antifungals in humans and the environment.

Antifungal drug resistance is a multifaceted clinical challenge, and when present, a primary cause of treatment failure in patients with severe fungal infections. Changing epidemiology, increasing resistance rates and a narrow antifungal armamentarium may further underline the required attention on resistance particularly within the most prevalent invasive fungal infections caused by Candida yeasts and Aspergillus moulds. In Denmark, the resistance epidemiology remains to be fully elucidated.

Recurrent prosthetic valve endocarditis caused by Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus).

We report Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus) causing recurrent prosthetic valve endocarditis. The fungus was the sole agent detected during replacement of a mechanical aortic valve conduit due to abscess formation.

In Vitro Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms.

ASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity against Aspergillus and Candida glabrata. We compared its in vitro activity against wild-type and azole-resistant A.

In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order.

The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole.

Discovery of a sexual stage in Trichophyton onychocola, a presumed geophilic dermatophyte isolated from toenails of patients with a history of T. rubrum onychomycosis.

Trichophyton onychocola is a recently described geophilic dermatophyte that has been isolated from a toenail of Czech patient with a history of onychomycosis due to T. rubrum and clinical suspicion of relapse. In this study, we report a similar case from Denmark in an otherwise healthy 56-year-old man.

Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations.

Objectives: The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance.

Methods: Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest.

Echinocandin failure case due to a previously unreported FKS1 mutation in Candida krusei.

Echinocandins are the preferred therapy for invasive infections due to Candida krusei. We present here a case of clinical failure involving C. krusei with a characteristic FKS1 hot spot mutation not previously reported in C.

Stepwise development of a homozygous S80P substitution in Fks1p, conferring echinocandin resistance in Candida tropicalis.

Three Candida tropicalis isolates were obtained from a patient with acute lymphoblastic leukemia. The first isolate was susceptible to all drug classes, while isolates 2 and 3, obtained after 8 and 8.5 weeks of caspofungin treatment, respectively, were resistant to the three echinocandins.

Evaluation of caspofungin susceptibility testing by the new Vitek 2 AST-YS06 yeast card using a unique collection of FKS wild-type and hot spot mutant isolates, including the five most common candida species.

FKS mutant isolates associated with breakthrough or failure cases are emerging in clinical settings. Discrimination of these from wild-type (wt) isolates in a routine laboratory setting is complicated. We evaluated the ability of caspofungin MIC determination using the new Vitek 2 AST-Y06 yeast susceptibility card to correctly identify the fks mutants from wt isolates and compared the performance to those of the CLSI and EUCAST reference methods.

In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration.

Azole resistance in Aspergillus terreus isolates was explored. Twenty related (MB) and 6 unrelated A. terreus isolates were included.

Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations.

We recently observed that the micafungin MICs for some Candida glabrata fks hot spot mutant isolates are less elevated than those for the other echinocandins, suggesting that the efficacy of micafungin may be differentially dependent on such mutations. Three clinical C. glabrata isolates with or without (S3) fks hot spot mutations R83 (Fks2p-S663F) and RR24 (Fks1p-S629P) and low, medium, and high echinocandin MICs, respectively, were evaluated to assess the in vivo efficacy in an immunocompetent mouse model using three doses of each echinocandin.

Molecular diagnosis of dermatophyte infections.

Purpose Of Review: Recent advances in the molecular diagnostics of dermatophytosis may improve speed, specificities and sensitivities. This review provides an update on the current available molecular techniques for the diagnosis of dermatophytosis.

Recent Findings: Molecular diagnostics of dermatophytosis relate to the direct detection of dermatophyte DNA in clinical specimens.

Echinocandin susceptibility testing of Candida isolates collected during a 1-year period in Sweden.

The susceptibilities of Candida isolates to the echinocandins anidulafungin, caspofungin, and micafungin were determined by using the recently revised CLSI breakpoints and Etest on 238 clinical bloodstream Candida isolates collected between September 2005 and August 2006. The isolates represent approximately 95% of all non-albicans Candida bloodstream infections and one-third of Candida albicans bloodstream infections during this 1-year period in Sweden. The collection included 81 C.

Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance.

Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among Aspergillus fumigatus isolates. Clinical and demographic data were also analyzed. A total of 3,336 respiratory samples from 287 CF patients were collected during two 6-month periods in 2007 and 2009.

Candida palmioleophila: characterization of a previously overlooked pathogen and its unique susceptibility profile in comparison with five related species.

Candida palmioleophila has previously been misidentified as C. famata or C. guilliermondii.