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Advances in Therapy Aug 2023Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating... (Review)
Review
Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics.
Topics: Humans; Natamycin; Antifungal Agents; Keratitis; Eye Infections, Fungal; Cornea
PubMed: 37289410
DOI: 10.1007/s12325-023-02541-x -
European Review For Medical and... Oct 2023In response to a range of stimuli, neutrophils produce web-like structures known as neutrophil extracellular traps (NETs). The benefits of NETs in pathogen control are... (Review)
Review
In response to a range of stimuli, neutrophils produce web-like structures known as neutrophil extracellular traps (NETs). The benefits of NETs in pathogen control are commonly offset by excessive release as part of a pro-inflammatory response, as shown in several disorders. The discovery of potential drugs that regulate NET release has helped to enhance our understanding of the role of NETs in immunological protection, inflammatory diseases, and autoimmune disorders. Emerging evidence has indicated that antimicrobials play an immunomodulatory role by influencing the levels of circulating NETs. Herein, we address NETosis in several disorders and detail the mechanisms of NET-mediated damage in infections. We also aim to evaluate recent evidence on the effects of antimicrobials on NET levels. Relevant keywords were searched in PubMed. Studies were evaluated for their relevance, and a narrative review was written accordingly. Several antibiotics, including beta-lactams and cephalosporins, alter NET formation and degradation in a protective manner, resulting in minimal host organ damage. Additionally, some studies have highlighted the immunomodulatory effects of antivirals and antifungals on NET. Further studies are needed to fully understand the clinical implications of NET-antimicrobial interactions and their underlying mechanisms.
Topics: Humans; Extracellular Traps; Neutrophils; Autoimmune Diseases; Antifungal Agents; Anti-Bacterial Agents
PubMed: 37916323
DOI: 10.26355/eurrev_202310_34129 -
PLoS Neglected Tropical Diseases Jul 2023Candida haemulonii complex-related species are pathogenic yeasts closely related to Candida auris with intrinsic antifungal resistance, but few epidemiological data are... (Review)
Review
BACKGROUND
Candida haemulonii complex-related species are pathogenic yeasts closely related to Candida auris with intrinsic antifungal resistance, but few epidemiological data are available.
METHODOLOGY/PRINCIPAL FINDINGS
We analyzed clinical and demographic characteristics of patients with fungemia due to C. haemulonii complex and related species (C. pseudohaemulonii, C. vulturna) reported in France during 2002-2021, and compared them to data of C. parapsilosis fungemia, as they all can be commensal of the skin. We also conducted a study on adult inpatients and outpatients colonized by C. haemulonii complex, managed at the University Hospital of Martinique during 2014-2020. Finally, we performed a literature review of fungemia due to C. haemulonii complex and related species reported in Medline (1962-2022). In total, we identified 28 fungemia due to C. haemulonii complex in France. These episodes were frequently associated with bacterial infection (38%) and high mortality rate (44%), and differed from C. parapsilosis fungemia by their tropical origin, mainly from Caribbean and Latin America. All isolates showed decreased in vitro susceptibility to amphotericin B and fluconazole. In Martinique, we found that skin colonization was frequent in the community population, while colonization was strongly associated with the presence of foreign devices in ICU patients. The literature review identified 274 fungemia episodes, of which 56 were individually described. As in our national series, published cases originated mainly from tropical regions and exhibited high crude mortality.
CONCLUSIONS/SIGNIFICANCE
Multidrug-resistant C. haemulonii complex-related species are responsible for fungemia and colonization in community and hospital settings, especially in tropical regions, warranting closer epidemiological surveillance to prevent a potential C. auris-like threat.
Topics: Adult; Humans; Antifungal Agents; Fungemia; Candida; Candidiasis; Microbial Sensitivity Tests; Hospitals, University
PubMed: 37523406
DOI: 10.1371/journal.pntd.0011453 -
Applied Microbiology and Biotechnology Dec 2024Fungal infections are increasing rapidly, and antifungal agents used in clinics are limited. Therefore, novel antifungal agents with high efficiency are urgently...
Fungal infections are increasing rapidly, and antifungal agents used in clinics are limited. Therefore, novel antifungal agents with high efficiency are urgently required. In this study, we investigated the antifungal activity of thonningianin A (THA), a natural compound that is widely found in plants. We first determined the activity of THA against Candida albicans, one of the most common fungal pathogens, and found that THA showed antifungal activity against all C. albicans tested, including several fluconazole-resistant isolates. THA also inhibits the growth of non-Candida albicans species. In addition, THA displayed antibiofilm activity and could not only inhibit biofilm formation but also destroy mature biofilms. The in vivo antifungal efficacy of THA was confirmed in a Galleria mellonella infection model. Further studies revealed that THA could enhance intracellular reactive oxygen species (ROS) production and regulate the transcription of several redox-related genes. Specifically, caspase activity and expression of CaMCA1, a caspase-encoding gene in C. albicans, were remarkably increased upon THA treatment. Consistent with this, in the presence of THA, the Camca1 null mutant displayed higher survival rates and reduced caspase activity compared to the wild-type or CaMCA1-reintroduced strains, indicating an important role of CaMCA1 in the antifungal activity of THA. Taken together, our results indicate that THA possesses excellent antifungal activity and may be a promising novel antifungal candidate. KEY POINTS: • THA exhibits activity against Candida species, including fluconazole-resistant isolates • THA inhibits biofilm formation and destroys mature biofilm • Elevated ROS production and CaMCA1-mediated caspase activity are involved in the antifungal mechanisms of THA.
Topics: Candida albicans; Antifungal Agents; Fluconazole; Reactive Oxygen Species; Caspases; Biofilms; Microbial Sensitivity Tests; Hydrolyzable Tannins
PubMed: 38212967
DOI: 10.1007/s00253-023-12996-1 -
Frontiers in Cellular and Infection... 2023-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence,... (Review)
Review
-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence, development of resistance, and poor penetration into the biofilm matrix. Various predisposition factors are molecular drivers that lead to the dysbiosis of normal microflora of the vagina, upregulation of central metabolic pathways, morphogenesis, hyphal extension, adhesion, invasion, and biofilm formation leading to chronic infection and recurrence. Hence, it is crucial to understand the molecular mechanism behind the virulence pathways driven by those drivers to decode the drug targets. Finding innovative solutions targeting fungal virulence/biofilm may potentiate the antifungals at low concentrations without affecting the recurrence of resistance. With this background, the present review details the critical molecular drivers and associated network of virulence pathways, possible drug targets, target-specific inhibitors, and probable mode of drug delivery to cross the preclinical phase by appropriate models.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Candida albicans; Antifungal Agents; Vagina; Virulence
PubMed: 37900321
DOI: 10.3389/fcimb.2023.1245808 -
Emerging Infectious Diseases Jul 2023Candida vulturna belongs to the Candida haemulonii species complex and is phylogenetically related to C. auris. We report a C. vulturna outbreak among persons in Shanxi...
Candida vulturna belongs to the Candida haemulonii species complex and is phylogenetically related to C. auris. We report a C. vulturna outbreak among persons in Shanxi Province, China, during 2019-2022. Isolates were resistant to multiple antifungal drugs and exhibited enhanced adhesion and biofilm formation properties.
Topics: Candida; Candidiasis; Antifungal Agents; China; Microbial Sensitivity Tests
PubMed: 37347816
DOI: 10.3201/eid2907.230254 -
Emerging Infectious Diseases Jul 2023We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris... (Review)
Review
We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.
Topics: Humans; Candida; Antifungal Agents; Candida auris; Israel; COVID-19; Candidiasis, Invasive; Disease Outbreaks; Hospitalization; Microbial Sensitivity Tests
PubMed: 37347492
DOI: 10.3201/eid2907.221888 -
Journal of Infection and Public Health Oct 2023Candida auris (CA) is an emerging fungus, classified as an urgent global health threat, that resists common antifungal drugs and decontamination procedures;...
BACKGROUND
Candida auris (CA) is an emerging fungus, classified as an urgent global health threat, that resists common antifungal drugs and decontamination procedures; identification requires specific tools; transmissibility and mortality are high in healthcare settings. Infection and colonisation can be long-lasting, leading to problems in isolation procedures and the risk of outbreaks. This study aims to evaluate publication and citation related metrics, identify major keywords and topics, and assess geographic distribution of published articles.
METHODS
A list of all publications containing "Candida auris" in all fields was extracted from Web Of Science on date 2023/01/02. Bibliometric analysis was conducted using the bibliometrix and biblioshiny packages on RStudio.
RESULTS
Total publications (TP) were 1283 with an annual growth rate of 53.91%. Total citations were 27854, with an average of 21.71 citations per paper. The core sources are 9 out of 322, according to Bradford's law. In only 42 countries where CA was identified, articles on the topic were published (89%). The origin of TP is concentrated in high-income countries (68.22%). Trending topics about CA include epidemiology, identification and resistance.
CONCLUSION
Our analysis shows a growing interest in scientific literature on the topic of CA, led by Europe. In some countries where CA has been identified, no papers have been published. Despite the multidrug-resistance of CA, the topic of therapy is not much debated. Our findings highlight the need to increase focus on CA in order to promote health systems' preparedness and to properly address the spread of this worrisome pathogen.
Topics: Humans; Global Health; Health Promotion; Bibliometrics; Antifungal Agents; Candida
PubMed: 37647837
DOI: 10.1016/j.jiph.2023.08.012 -
Molecules (Basel, Switzerland) Feb 2024In the relentless pursuit of innovative therapeutic agents, natural products have emerged as a transformative avenue in the battle against infectious diseases [...].
In the relentless pursuit of innovative therapeutic agents, natural products have emerged as a transformative avenue in the battle against infectious diseases [...].
Topics: Antifungal Agents; Biological Products; Anti-Bacterial Agents; Antiviral Agents
PubMed: 38398577
DOI: 10.3390/molecules29040825 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Invasive Fungal Infections; Antifungal Agents
PubMed: 37520443
DOI: 10.3389/fcimb.2023.1227837