Emerging Resistance Among Candida Species: Trends and Treatment Considerations for Candidemia
Robert C. Owens, Lautenbach Ebbing in Antimicrobial Resistance, 2007
In summary, candidemia continues to be an important cause of healthcare-associated infections and, despite the introduction of various antifungal treatments, it remains a significant cause of morbidity and mortality. There has been an important shift in the epidemiology of candidemia with a decrease in bloodstream infections due to C. albicans and an increase in C. glabrata, which is often associated with fluconazole resistance. Other causes of a minority of candidemia, including C. krusei, C. parapsilosis, C. lusitaniae, C. guilliermondii, and C. rugosa, have also been associated with antifungal resistance. Given the emergence of antifungal resistance, as well as studies suggesting the importance of initiating appropriate antifungal treatment in a timely manner, quickly diagnosing and performing susceptibility testing of these pathogens has become crucial. The treatment of candidemia has also become more challenging, with agents other than fluconazole being considered as primary options.
Antifungal drug resistance: Significance and mechanisms
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
Resistance to commonly used antifungals (e.g., azoles, polyenes, echinocandins, allylamines) is a significant problem in nosocomial infections (including invasive and superficial mycoses), as well as those associated with indwelling devices like central venous catheters, urinary catheters, and contact lenses (fungal keratitis). Fungal resistance has been reported even for newer antifungals, such as the echinocandins, underscoring the importance of gaining insight into the mechanisms of antifungal resistance. This chapter briefly describes the methods used to evaluate antifungal susceptibility of fungi, reviews the significance of antifungal resistance, and summarizes recent advances in identification of the underlying mechanisms.
Rational Use of Antifungals for Invasive Fungal Infections in the Institutional Setting
Robert C. Owens, Paul G. Ambrose, Charles H. Nightingale in Antibiotic Optimization, 2004
Another manner to assess the potential impact of antifungal use is surveillance of the epidemiology of fungal infections at a particular institution. This practice, commonly employed for bacterial infections, is readily available at many institutions in the form of an antibiogram. Microbiology laboratories that are equipped with the appropriate technology can provide data on the pattern of fungal infections on given wards and the susceptibilities of those pathogens. Tracking trends in antifungal resistance, especially among Candida spp, may aid in the selection of appropriate empiric therapies and potentially affect patient outcomes.
Effects of antifungal agents on the fungal proteome: informing on mechanisms of sensitivity and resistance
Published in Expert Review of Proteomics, 2021
The application of proteomics to characterize the effects of antifungal agents on pathogenic fungi has also deepened our understanding of their impact on their targets, in an unbiased fashion. By using this global approach to characterize the effects of antifungals on susceptible fungi, we can also potentially identify off-target effects that could be triggered in host cells, which may contribute to drug toxicity. Furthermore, investigation of antifungal resistance using this approach has the potential to identify new mechanisms that contribute to drug sensitivity or resistance. This review aims to survey proteomic studies that have been carried out to date, which expand our understanding of the mechanisms of action and resistance of antifungal agents, including both clinical drugs and fungal-derived biomolecules with antifungal activity (Table 1). Limited proteomic investigations have been carried out to date on agriculturally relevant fungicides so this review will mainly cover effects on medically relevant fungi. Information has been collated through searches of literature databases (Pubmed, Google Scholar), predominantly focusing on publications from 2010 to 2020. Where relevant, we aim to contextualize the results from these analyses with information from supporting studies, to generate new or reinforce existing hypotheses in relation to antifungal activity and resistance, as well as to highlight gaps for potential future investigations in this field.
In vitro and in vivo anti-Candida activity of citral in combination with fluconazole
Published in Journal of Oral Microbiology, 2022
Katherine Miranda-Cadena, Cristina Marcos-Arias, Aitzol Perez-Rodriguez, Iván Cabello-Beitia, Estibaliz Mateo, Elena Sevillano, Lucila Madariaga, Guillermo Quindós, Elena Eraso
With regard to the involvement of citral in the expression of the ERG11 gene, our findings were not conclusive. The relative changes in expression were not significant in any case, despite the fact that a slight ERG11 upregulation was observed. This could be due to the low concentrations of fluconazole used in this study [47]. However, in a previous study using carvacrol, down-regulated expression of ERG3 and ERG11 was described at different concentrations (IC, 25 mg/L, and 0.5× IC) [48]. Although ERG11 encodes an essential enzyme in the C. albicans pathway and the Hot-spot mutations and its overexpression are associated with fluconazole resistance, there are about 20 genes involved in the ergosterol biosynthesis, which have not been included in this study. Hence, if citral interferes with the ergosterol pathway, it should be independent to ERG11 or likely dose dependent, and other ERG genes should be considered. In addition, it is relevant to note that antifungal resistance is often the result of the sum of several mechanisms, and further study would be necessary for a better understanding.
Strengths and caveats of identifying resistance genes from whole genome sequencing data
Published in Expert Review of Anti-infective Therapy, 2022
Brian M. Forde, David M. P. De Oliveira, Caitlin Falconer, Bianca Graves, Patrick N. A. Harris
This review has a focus on bacterial species, but WGS has been used extensively to delineate resistance in non-bacterial pathogens. The use of sequencing to detect drug-resistant variants and guide the selection of antiviral regimen is standard practice in the management of HIV, with well curated databases for the clinical interpretation of genotypic resistance (e.g. https://hivdb.stanford.edu). Beyond the limited sequencing of genes that encode the targets of specific antiviral agents (e.g. HIV pol gene), WGS can capture all resistant variants and has a higher sensitivity for the detection of low-frequency minority resistance variants in mixed populations which may lead to treatment failure [124]. Molecular detection of antifungal resistance can overcome limitations of phenotypic susceptibility testing including long turnaround time, poor growth rates and a lack of interpretive criteria [125]. Mutations associated with echinocandin resistance in Candida sp. and azole resistance in A. fumigatus have been well characterized through WGS and demonstrate high correlation with phenotype and, in the case of FKS mutations, therapeutic failure [126]. WGS surveillance has also been used to detect the emergence of resistance to artemisinin-based combination therapies (ACTs) in Plasmodium falciparum and guide regional empirical treatment recommendations [127].
Related Knowledge Centers
- Antibiotic
- Antifungal
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- Horizontal Gene Transfer
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