Antifungals: From Pharmacokinetics to Clinical Practice

Antibiotics, Journal Year: 2023, Volume and Issue: 12(5), P. 884 - 884

Published: May 9, 2023

The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until present day, AmB has been considered to be a hallmark treatment invasive systemic fungal infections. Nevertheless, success were associated severe adverse effects which stimulated development new such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines echinochandins. However, all these presented one or more limitations reactions, administration route recently resistance. To worsen this scenario, there an increase infections, especially infections that are particularly difficult diagnose treat. In 2022, World Health Organization (WHO) published first priority pathogens list, alerting people increased incidence risk mortality/morbidity. report also emphasized need rationally existing develop drugs. review, we performed overview history antifungals their classification, mechanism action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics clinical applications. parallel, addressed contribution fungi biology genetics resistance Considering drug effectiveness depends on mammalian host, provide roles therapeutic monitoring pharmacogenomics means improve outcome, prevent/reduce toxicity prevent emergence Finally, main characteristics.

Language: Английский

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Pathogenic Drug Resistant Fungi: A Review of Mitigation Strategies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1584 - 1584

Published: Jan. 13, 2023

Fungal pathogens cause significant human morbidity and mortality globally, where there is a propensity to infect vulnerable people such as the immunocompromised ones. There increasing evidence of resistance antifungal drugs, which has implications for cutaneous, invasive bloodstream infections. The World Health Organization (WHO) published priority list fungal in October 2022, thus, highlighting that crisis point been reached pressing need address solutions. This review provides timely insight into challenges on topic drug along with discussing effectiveness established disease mitigation modalities approaches. also elucidate cellular molecular mechanisms inform effective decontamination approaches are medical device processing sterilization, but presence pathogenic fungi recalcitrant biofilms can lead challenges, particularly during cleaning. Future design ideas implantable reusable devices should consider materials appropriates disinfection, it relevant, sterilization. Preventing growth mycotoxin-producing foods through use appropriate end-to-end processes advisable, mycotoxins challenging eliminate once they have formed.

Language: Английский

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Identification of Virulence Factors in Isolates of Candida haemulonii, Candida albicans and Clavispora lusitaniae with Low Susceptibility and Resistance to Fluconazole and Amphotericin B

Microorganisms, Journal Year: 2024, Volume and Issue: 12(1), P. 212 - 212

Published: Jan. 20, 2024

Emerging life-threatening multidrug-resistant (MDR) species such as the C. haemulonii complex, Clavispora lusitaniae (sin. lusitaniae), and other Candida are considered an increasing risk for human health in near future. (1) Background: Many studies have emphasized that increase drug resistance can be associated with several virulence factors its knowledge is also essential developing new antifungal strategies. (2) Methods: Hydrophobicity, adherence, biofilm formation, lipase activity, to osmotic stress, ‘in vivo’ on G. mellonella larvae were studied isolates of haemulonii, albicans, low susceptibility fluconazole amphotericin B. (3) Results: Intra- interspecies variability observed. showed high hydrophobicity ability adhere form biofilm. was less hydrophobic, biofilm-formation-strain-dependent, did not show activity. Larvae inoculated albicans displayed significantly higher mortality rates than those infected lusitaniae. (4) Conclusions: The biofilms their hydrophobic capacity, adapt infect within vivo model, observed these non-wild-type isolates, shows marked features. Since define related development fungi few antifungals available clinical use, differences physiology cells must develop therapies.

Language: Английский

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Comprehensive Review of Aflatoxin and Ochratoxin A Dynamics: Emergence, Toxicological Impact, and Advanced Control Strategies

Foods, Journal Year: 2024, Volume and Issue: 13(12), P. 1920 - 1920

Published: June 18, 2024

Filamentous fungi exhibit remarkable adaptability to diverse substrates and can synthesize a plethora of secondary metabolites. These metabolites, produced in response environmental stimuli, not only confer selective advantages but also encompass potentially deleterious mycotoxins. Mycotoxins, exemplified by those originating from Alternaria, Aspergillus, Penicillium, Fusarium species, represent challenging hazards both human animal health, thus warranting stringent regulatory control. Despite frameworks, mycotoxin contamination remains pressing global challenge, particularly within cereal-based matrices their derived by-products, integral components diets. Strategies aimed at mitigating multifaceted approaches, including biological control modalities, detoxification procedures, innovative interventions like essential oils. However, hurdles persist, underscoring the imperative for interventions. This review elucidated prevalence, health ramifications, paradigms, evolving preventive strategies about two prominent mycotoxins, aflatoxins ochratoxin A. Furthermore, it explored emergence new fungal biocontrol methods using lactic acid bacteria mustard oil, emphasizing efficacy spoilage production. Through an integrative examination these facets, this endeavored furnish comprehensive understanding challenges posed emergent poised ameliorate its impact on food feed safety.

Language: Английский

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Comprehensive In Vitro and Molecular Docking Analysis of Antioxidant and Antimicrobial Properties of Salvia officinalis L. Extracts and Essential Oils

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141621 - 141621

Published: Jan. 1, 2025

Language: Английский

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Lipid-based nanoformulations in onychomycosis therapy: addressing challenges of current therapies and advancing treatment

RSC Advances, Journal Year: 2025, Volume and Issue: 15(10), P. 7799 - 7825

Published: Jan. 1, 2025

Onychomycosis significantly impacts approximately 20% of the global population.

Language: Английский

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Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 2^3 Full Factorial Design

Polymers, Journal Year: 2023, Volume and Issue: 15(4), P. 995 - 995

Published: Feb. 16, 2023

Itraconazole (ITZ) is a triazole antifungal agent characterized by broad-spectrum activity against fungal infections. The main drawback of ITZ, when applied topically, the low skin permeability due to stratum corneum, outermost layer skin, which represents barrier for drug penetration. Therefore, this study aimed prepare itraconazole as transferosomes (ITZ-TFS) overcome function skin. ITZ-TFSs were prepared thin lipid film hydration technique using different surfactants, sodium lauryl sulfate (SLS) and deoxycholate (SDC). ITZ-TFS evaluated entrapment efficiency (EE) %, particle size, polydispersity index (PDI), zeta potential, in vitro release obtain an optimized formula. surface morphology formula was determined transmission electron microscope (TEM). formulation form gel hydroxyl propyl methyl cellulose (HPMC) base. homogeneity, content, spreadability, pH, comparison with free ITZ gel. formulations exhibited high EE% ranging from 89.02 ± 1.65% 98.17 1.28% size 132.6 2.15 nm 384.1 3.46. PDI all less than 0.5 had negative potential. TEM image (ITZ-TFS4) showed spherical vesicles smooth surface. gels good acceptable content. higher zone inhibition. successfully TFSs drug.

Language: Английский

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Global Burden of Fungal Infections and Antifungal Resistance from 1961 to 2024: Findings and Future Implications

Pharmacology &amp Pharmacy, Journal Year: 2024, Volume and Issue: 15(04), P. 81 - 112

Published: Jan. 1, 2024

Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires One Health approach including Stewardship (AFS). This study aimed to comprehensively review studies published on fungal infections and recommend solutions address this growing problem. Materials Methods: was narrative that conducted using papers infections, AFR, AFS between January 1961 March 2024. The literature searched PubMed, Google Scholar, Web of Science, EMBASE. Results: found there has been an increase in globally, patients. Due proportionate the use antifungal agents prevent treat infections. increased worsened contributing morbidity mortality. Globally, have contributed 150 million annually 1.7 deaths per year. By year 2023, over 3.8 people died from remains challenge because treatment antifungal-resistant difficult. Finally, exacerbated by limited number invasive Conclusion: results indicated are prevalent across humans, animals, agriculture, environment. provision such as improving awareness conducting further research discovery new agents, implementing programs. If not addressed, mortality associated will continue rise future.

Language: Английский

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Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(7), P. 2356 - 2380

Published: June 7, 2024

Fungal keratitis (FK) is a severe ocular condition resulting from corneal infection that prevalent in tropical countries, particularly developing regions of Asia and Africa. Factors like lens misuse, inappropriate steroid use, diagnostic challenges have provoked the epidemic. FK causes significant vision impairment, scarring, deformities. Accurate pathological diagnosis crucial for effective therapeutic intervention. Topical antifungal therapy with surface healing medications proves preventing fungal-borne ulcers. Managing requires comprehensive understanding fungal pathogenesis, guiding formulation strategies preventive measures to curb global blindness. This review provides in-depth insights into FK, covering etiology, epidemiology, interventions, resistance, limitations, prevention, future perspectives on disease management.

Language: Английский

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Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 201 - 201

Published: Feb. 2, 2024

The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance on list top ten threats global health. Immunomodulatory peptides that target a pathogen modulate immune system simultaneously are promising for development preventive therapeutic molecules. Since investigating innate immunity in insects has led prominent achievements human immunology, such as toll-like receptor (TLR) discovery, we used capacity immunomodulatory arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short sequences encrypted 643 from 55 foe-to-friend arthropods. critical features involved efficacy safety were calculated. Finally, 76 safe immunomodulators identified. Then, molecular docking simulation studies defined most optimal peptide ligands among all cell-surface TLRs. SPalf2-453 crab cell-penetrating immunoadjuvant antiviral properties. interacts TLR1/2 heterodimer. SBsib-711 blackfly TLR4/MD2 ligand cancer immunoadjuvant. In addition, binds CD47 PD-L1 tumor cells, which applicable immunotherapy checkpoint inhibitor. MRh4-679 shrimp broad-spectrum universal putative Th1/Th2-balanced response. We also implemented pathway enrichment analysis define fingerprints immunological signatures further vitro vivo immunogenicity reactogenicity measurements. Conclusively, combinatorial learning, docking, studies, well systems biology, open new opportunity multifunctional prophylactic lead peptides.

Language: Английский

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