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Related Concept Videos

Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
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Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).
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Anthelminthic Agents

Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
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Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
Overview of Fungi01:29

Overview of Fungi

Fungi are a diverse group of eukaryotes more closely related to animals than other eukaryotes. Fungal cell walls comprise chitin, a polysaccharide that provides structural strength, and glucans, which contribute to flexibility and integrity. Other polysaccharides, such as mannans and galactosans, may supplement or replace chitin in some fungi. These adaptations, along with their preference for acidic environments and tolerance for high osmotic pressure, enable fungi to thrive in various...
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Updated: Jun 2, 2026

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

Current perspectives on echinocandin class drugs.

David S Perlin1

  • 1Public Health Research Institute, New Jersey Medical School-UMDNJ, Newark, NJ 07103, USA. perlinds@umdnj.edu

Future Microbiology
|April 30, 2011
PubMed
Summary

Echinocandin antifungals inhibit fungal cell wall synthesis, showing high efficacy against Candida species and Aspergillus. Resistance mechanisms, like FKS mutations, are being addressed with updated breakpoints and new drug development.

Area of Science:

  • Mycology
  • Pharmacology
  • Biochemistry

Background:

  • Echinocandins (caspofungin, micafungin, anidulafungin) are key antifungal agents targeting fungal cell wall synthesis.
  • They inhibit β-1,3-D-glucan synthase, an enzyme absent in humans, leading to a favorable safety profile.
  • Echinocandins are effective against Candida species, including azole-resistant strains and biofilms, but are fungistatic against moulds.

Purpose of the Study:

  • To review the mechanism of action, spectrum of activity, and resistance patterns of echinocandin antifungal drugs.
  • To discuss the clinical implications of resistance mechanisms, particularly FKS mutations, and the evolution of susceptibility breakpoints.
  • To highlight emerging resistance pathways and future directions in glucan synthase inhibitor development.

Main Methods:

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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
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Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds

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  • Literature review of echinocandin antifungal agents.
  • Analysis of resistance mechanisms, including genetic mutations (FKS) and adaptive cellular responses.
  • Examination of pharmacokinetic/pharmacodynamic data and clinical breakpoints.

Main Results:

  • Echinocandins demonstrate potent activity against susceptible Candida and Aspergillus isolates with low resistance frequency.
  • FKS mutations in glucan synthase confer high-level resistance, necessitating revised clinical breakpoints.
  • FKS-independent resistance mechanisms involving Hsp90 and calcineurin pathways can also elevate MIC values.
  • Drug-induced cell wall alterations modulate host immune responses.

Conclusions:

  • Echinocandins remain vital antifungals, with ongoing research addressing resistance and improving therapeutic strategies.
  • Understanding resistance mechanisms is crucial for optimizing treatment and guiding the development of new glucan synthase inhibitors.
  • The development of novel, orally active glucan synthase inhibitors offers promising future therapeutic options.