Anti fungal agents essay Flashcards
Overall introduction?
Rephrase question and my interpretation
An example of the Importance is demonstrated by Candida bloodstream infection in adults are associated with longer stays in hospital, and larger costs the people in hospital without this infection, also an average person stays 1 month longer in hospital which $45,000 additional costs, excaerbating the problem of the infection. (Moran C, 2012)
At the forefront of clinical trial There 3 new triazoles, with extremely broad antifungal spectra of which oriconazole, which is the first approved and so far the most fully characterised of the three new triazoles is effective against Fusarium infections ,
and three are echinocandins, which inhibit synthesis of fun- gal cell wall polysaccharides – a new mode of action, in which caspofungin is effective against candida infections which have been processed from clinical trial (Brown AJ, 2003) for both of them
However, Antifungal resistance mechanisms that will be discussed can occur is associated with elevated minimum inhibitory concentrations, poorer clinical outcomes, and breakthrough infections during antifungal treatment and prophylaxis. (Pfaller MA, 2012)
Explain how will answer question
Introduction on fusarium species?
Fusarium species are ubiquitous and may be found in the soil, air and on plants.
can cause mycotoxicosis in humans following ingestion of food that has been colonized by the fungal organism.
generally affects immunocompromised individuals
Typical skin lesions may be painful red or violaceous nodules (Gupta AK, 2000)
Main paragraph part 1 on fusarium species?
Azole antifungals work by inhibiting the cytochrome P450 dependent enzyme lanosterol 14-alpha-demethylase, which converts lanosterol to ergosterol, the main sterol in the fungal cell membrane. Depletion of ergosterol damages the cell membrane resulting in cell death. (Brown AJ, 2003)
Main paragraph part 2 on fusarium species?
Development of azole resistance in fungi may occur through increased levels of the cellular target, upregulation of genes controlling drug efflux, alterations in sterol synthesis and decreased affinity of azoles for the cellular target. (Lupetti A, 2002)
This was demonstrated by ( Becher R, 2010) We allowed F. grami- nearum strain NRRL 13383 to adapt to an azole fungicide in vitro, applying a strongly growth-reducing but sublethal dose of tebuconazole
Two morphologically distinguishable azole-resistant phenotypes were recovered that differed with regard to levels of fitness, fungicide resistance, virulence, and mycotoxin production. Isolates of the adapted “phenotype 1” exhibited azole-specific cross-resistance, whereas “pheno- type 2” isolates displayed the phenomenon of multidrug resistance because the sensitivity to amine fungicides was also affected
Conclusion on fusarium species?
Main findings
What it means for public/businesses
positive and negative of the study
Introduction on candida?
Candida albicans is an opportunistic pathogen that is commonly found as a member of the human microflora. (Hogan DA, 2004)
Candidiasis is a common infection of the skin, oral cavity and esophagus, gastrointestinal tract, vagina and vascular system of humans. (Calderone RA, 2001)
From host recognition biomolecules (adhesins) to morphogenesis (the reversible transition between unicellular yeast cells and filamentous, growth forms flexibility that results in the adaptation of the organism to the hostile conditions imposed not only by the host but also by the physician treating the infection. (Calderone RA, 2001)
Main paragraph part 1 on candida?
The echinocandins are fungal secondary metabolites comprising a cyclic hexapeptide core with a lipid side- chain responsible for antifungal activity
The target for the echinocandins is the complex of proteins responsible for synthesis of cell wall b-1,3 glucan polysaccharides, via noncompetitive inhibition of the enzyme 1,3-β glucan synthase
Mechanistic details of glucan synthesis and its inhibition by echinocandins still remain obscure, largely because a membrane-associated protein complex is involved
(All Brown AJ, 2003)
Main paragraph part 2 on candida?
Niimi, 2016 found that The echinocandins are poor substrates for most multidrug efflux transporters. In a comprehensive study, it was found that C. albicans and S. cerevisiae strains hyper-expressing fungal ATP-binding cassette (ABC) or major facilitator superfamily (MFS) transporters showed only weak changes in echinocandin susceptibility
hence this a strength of the drug, bypassing resistance of efflux pumps
However, . A mechanism for clinically-relevant resistance is expected to reflect direct changes in drug-target interactions. Unfortunately, the mechanistic nature of echinocandin inhibition of glucan synthase is poorly understood, as is biochemistry of the glucan synthase complex found Douglas 2001
Conclusion on candida?
Main findings
What it means for public/businesses
positive and negative of the study
Overall conclusion?
state essay question and give answer
Say how ideas can be developed more in clinical trial
Describe weaknesses, but strengths as well
Practical application
Further study
Strong concluding sentence