Search

Objective: This study aims to present a case of persistent mycetoma caused by Scedosporium boydii and undertake a systematic literature overview to elucidate the clinical characteristics and antifungal treatment exhibited by such patients. Methods: We report the case of a 24-year-old female who sustained a Scedosporium boydii infection in her right foot over a decade ago following a nail puncture. Concurrently, a comprehensive literature overview was conducted on PubMed, focusing on documented cases of Scedosporium boydii infections with the intent of extracting relevant clinical data. Results: Our analysis revealed that post-transplantation, trauma, near drowning, corticosteroid administration, and prior surgical history were the main risk factors for Scedosporium boydii infection. Prevalent infection sites included skin/bone tissues, the central nervous system, and ocular regions. Among the 49 patients identified, 24 received itraconazole therapy and 25 received voriconazole, with no significant difference in patient outcomes (P = 0.158). Of these, 12 patients experienced treatment failure. Notably, prolonged antifungal treatment duration was identified as a protective factor against mortality in Scedosporium boydii infections [P = 0.022, OR(95%CI): 0.972(0.949–0.996)]. Conversely, a history of post-transplantation emerged as a potential risk factor for mortality[P = 0.046, OR(95%CI): 7.017(1.034–47.636)]. Conclusion: While uncommon, Scedosporium boydii infections carry a significant burden of morbidity and adverse outcomes. Heightened clinical vigilance is warranted in individuals presenting with risk factors for this pathogen. Timely and effective antifungal intervention is crucial, with both voriconazole and itraconazole demonstrating positive treatment outcomes for Scedosporium boydii infection. Therefore, prioritizing these antifungal agents should be considered a key therapeutic strategy in the management of this patient population. [ABSTRACT FROM AUTHOR]

Fungi (Neolentinus lepideus, Nl, and Trametes versicolor, Tv) impart wood rot, leading to economic and environmental issues. To overcome this issue, toxic chemicals are commonly employed for wood preservation, impacting the environment and human health. Surface coatings based on antimicrobial chitosan (CS) of high molar mass (145 × 105 Da) were tested as wood preservation agents using an innovative strategy involving ultra-pressurizing CS solutions to deposit organic coatings on wood samples. Before coating deposition, the antifungal activity of CS in diluted acetic acid (AcOOH) solutions was evaluated against the rot fungi models Neolentinus lepideus (Nl) and Trametes versicolor (Tv). CS effectively inhibited fungal growth, particularly in solutions with concentrations equal to or higher than 0.125 mg/mL. Wood samples (Eucalyptus sp. and Pinus sp.) were then coated with CS under ultra-pressurization at 70 bar. The polymeric coating deposition on wood was confirmed through X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM) images, and water contact angle measurements. Infrared spectroscopy (FTIR) spectra of the uncoated and coated samples suggested that CS does not penetrate the bulk of the wood samples due to its high molar mass but penetrates in the surface pores, leading to its impregnation in wood samples. Coated and uncoated wood samples were exposed to fungi (Tv and Nl) for 12 weeks. In vivo testing revealed that Tv and Nl fungi did not grow on wood samples coated with CS, whereas the fungi proliferated on uncoated samples. CS of high molar mass has film-forming properties, leading to a thin hydrophobic film on the wood surface (water contact angle of 118°). This effect is mainly attributed to the high molar mass of CS and the hydrogen bonding interactions established between CS chains and cellulose. This hydrophobic film prevents water interaction, resulting in a stable coating with insignificant leaching of CS after the stability test. The CS coating can offer a sustainable strategy to prevent wood degradation, overcoming the disadvantages of toxic chemicals often used as wood preservative agents. [ABSTRACT FROM AUTHOR]

SUMMARY: Presilphiperfolane‐type sesquiterpenes represent a unique group of atypical sesquiterpenoids characterized by their distinctive tricyclic structure. They have significant potential as lead compounds for pharmaceutical and agrochemical development. Herein, we utilized a transcriptomic approach to identify a terpene synthase (TPS) gene responsible for the biosynthesis of rare presilphiperfolane‐type sesquiterpenes in Inula lineariifolia, designated as IlTPS1. Through phylogenetic analysis, we have identified the evolutionary conservation of key motifs, including RR(x)8W, DDxxD, and NSE/DTE in IlTPS1, which are shared with other tricyclic sesquiterpene synthases in the TPS‐a subfamily of Asteraceae plants. Subsequent biochemical characterization of recombinant IlTPS1 revealed it to be a multiproduct enzyme responsible for the synthesis of various tricyclic sesquiterpene alcohols from farnesyl diphosphate (FPP), resulting in production of seven distinct sesquiterpenes. Mass spectrometry and nuclear magnetic resonance (NMR) spectrometry identified presilphiperfolan‐8β‐ol and presilphiperfol‐7‐ene as predominant products. Furthermore, biological activity assays revealed that the products from IlTPS1 exhibited a potent antifungal activity against Nigrospora oryzae. Our study represents a significant advancement as it not only functionally identifies the first step enzyme in presilphiperfolane biosynthesis but also establishes the heterologous bioproduction of these unique sesquiterpenes. Significance Statement: Our research has uncovered the molecular mechanism responsible for the synthesis of rare, bridged tricyclic sesquiterpenes by IlTPS1. Furthermore, we have established their bioproduction and assessed their antimicrobial properties. This study serves as a promising example of how unique sesquiterpene natural products can be harnessed and leveraged in the pharmaceutical and agrochemical sectors for various applications. [ABSTRACT FROM AUTHOR]

Background Cerebral aspergillosis (CA) is associated with high mortality. According to the European Conference on Infections in Leukemia and the European Society of Clinical Microbiology and Infectious Diseases guidelines, the recommended first-line treatment for all forms of aspergillosis is voriconazole or isavuconazole. However, little is known about the efficacy and safety of isavuconazole in CA. Methods We conducted a European multicenter retrospective study of patients treated with isavuconazole for proven or probable CA between 2014 and 2022 and compared the outcomes with those of weighted control groups from the previously published French national cohort of CA, the Cerebral Aspergillosis Lesional Study (CEREALS). Results Forty patients from 10 countries were included. The main underlying conditions were hematological malignancies (53%) and solid-organ transplantation (20%). Isavuconazole was administered as a first-line treatment to 10 patients, primarily in combination therapy, resulting in control of CA in 70% of these cases. Thirty patients received isavuconazole after a median of 65 days on another therapy, mostly because of side effects (50%) or therapeutic failure (23%) of the previous treatment. Predominantly given as monotherapy, it achieved control of CA in 73% of the patients. Seventeen patients (43%) underwent neurosurgery. When measured, isavuconazole levels were low in cerebrospinal fluid but adequate in serum and brain tissue. Isavuconazole toxicity led to treatment interruption in 7.5% of the patients. Twelve-week mortality was 18%. Comparison with the CEREALS cohort showed comparable survival in patients receiving isavuconazole or voriconazole as a first-line treatment. Conclusions Isavuconazole appears to be a well-tolerated treatment. Mortality of CA treated with isavuconazole is similar to that reported with voriconazole. [ABSTRACT FROM AUTHOR]

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was −5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration. [ABSTRACT FROM AUTHOR]

Background: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. Methods: This retrospective cohort study included patients treated at Peru's oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. Results: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87–23.24, p = 0.003). Conclusions: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death. [ABSTRACT FROM AUTHOR]

Background: Candida spp. are the most common cause of opportunistic fungal infections and are associated with a high mortality rate worldwide. In Palestine, the prevalence of Candida spp. infections remains elusive. Methods: We performed our study at two hospitals in Palestine (Istishari Arab Hospital, and Najah National University Hospital). All patients diagnosed with candidiasis during the year 2022 have participated in the study. The prevalence of Candida spp., their distribution, and the activity of selected antifungals against Candida pathogens were assessed. In combination with phenotypic properties, Candida isolates were identified and tested for antifungal susceptibility using the colorimetric VITEK-2 Compact system. Results: Our results showed that the prevalence of Candida spp. among infected samples was 11.6%. A total of eleven different Candida spp. were identified. Among these isolates, C. albicans (46.54%) was the most frequent, followed by C. glabrata (16.14%), C. tropicalis (13.83%), C. parapsilosis (4.82%), C. krusei (3.56%), C. dubliniensis (2.09%), C. ciferrii (1.67%), C. lusitaniae (0.83%), C. guilliermondii (0.62%), C. kefyer (0.41%) and C. spherica (0.20%). Among C. albicans, all isolates were 100% susceptible to fluconazole and micafungin. The susceptibility rates to Amphotericin B and flucytosine were 95% and 99%, respectively. The susceptibility rates of non-albicans Candida spp. (NAC) to fluconazole, voriconazole, amphotericine B, caspofungin, flucytosine and micafungin were 70%, 99%, 97%, ,72%, 92% and 100%, respectively. The incidence of Candida infections was higher in the intensive care unit and surgery department as compared to other hospital departments. Conclusions: Four pathogens are responsible for the most invasive infections: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. A notable characteristic of this study was the high frequency of NAC species which were often more resistant to antifungal agents. A quick and accurate system like Vitek 2 compact was suggested for the careful species identification of clinical isolates of Candida. We suggest that continued surveillance of species distribution and susceptibility to antifungals will enhance future burden estimates and assist in evaluating preventative measures' effectiveness. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Mycobacterium (M.) chelonae is responsible for a half of relatively rare nontuberculous mycobacteria (NTM) keratitis. We report a case of M. chelonae keratitis in a woman following sclerocorneal suture extraction after cataract surgery. Results: A 70-year-old woman presented with a red eye and corneal infiltration of her left eye six weeks following sclerocorneal suture extraction after an elective cataract surgery in another institute. She complained of a sharp, cutting pain and photophobia. Since initial corneal scrapes and conjunctival swabs proved no pathogen using culture and PCR methods, non-specific antibiotics and antifungal agents were administered. As keratitis was complicated by an inflammation in the anterior chamber and vitreous, samples of the vitreous fluid were sent for microbiologic examination. DNA of Epstein-Barr virus (EBV) was repeatedly detected. Since the intrastromal abscess had formed, corneal re-scrapings were performed and M. chelonae was detected using culture, MALDI-TOF MS and PCR methods. Therapy was changed to a combination of oral and topical clarithromycin, intravitreal, topical and intracameral amikacin, and oral and topical moxifloxacin. The successful therapy led to stabilization. The optical penetrating keratoplasty was performed and no signs of the infection recurrence were found. Conclusions: The diagnosis of nontuberculous mycobacterial keratitis is difficult and often delayed. An aggressive and prolonged antimicrobial therapy should include systemic and topical antibiotics. Surgical intervention in the form of corneal transplantation may be required in the active and nonresponsive infection. In the presented case this was necessary for visual rehabilitation due to scarring. [ABSTRACT FROM AUTHOR]

Azo switches are widely employed as essential components in light-responsive systems. Here, we develop an azo-fluorescent switch that is visible light-responsive and its light-responsive processes can be monitored using fluorescence imaging. Visible light irradiation promotes isomerization, accompanied by changes in fluorescence that enable the process to be monitored through fluorescence imaging. Furthermore, we document that the nanocavity size of liposome encapsulated nanoparticles containing azo changes in the isomerization process and show that this change enables construction of a light-responsive nanoplatform for optically controlled release of antimycotics. Also, natural light activation of nanoparticles of the switch loaded with an antimycotic agent causes death of Rhizoctonia solani. The results show that these nanoparticles can double the holding period in comparison to small molecule antimycotics. The strategy used to design the imaging-guided light-controlled nano-antimycotic release system can be applicable to protocols for controlled delivery of a wide variety of drugs. Azo compounds are widely used in the photo-induced regulation in biological systems. Here, the authors develop a nanosystem comprising an azo-fluorescent switch, in which the visible light-responsiveness enables the control of the system and monitorization using fluorescence imaging. [ABSTRACT FROM AUTHOR]

Objective: Small molecule calcitonin gene-related peptide (CGRP) antagonists such as rimegepant, ubrogepant, and atogepant have been approved for migraine treatment and/or prevention. These molecules are metabolized by cytochrome P-450 3A4 (CYP3A4) enzymes in vivo, hence they are contraindicated or recommended to be avoided in combination with strong/moderate CYP3A4 inhibitors, namely posaconazole (strong) and isavuconazonium (moderate). However, no literature has been published on the impact this interaction has on patient safety and tolerability. In this case series, we report five cases in which CGRP antagonists and azole antifungal therapy were given concurrently, to provide real-world outcomes of this interaction. Data sources: Electronic medical records at our hospital system were reviewed between January 2021 and December 2023 to find patients who met the criteria of hematological malignancy, taking CGRP-antagonist and azole antifungal therapy. Records were then further investigated to find cases where CGRP antagonists and azole antifungals were used concomitantly. Data summary: Concurrent use of CGRP antagonists and azole antifungal therapy was feasible for patients with migraines and hematological malignancies. None of the patients experienced any grade 3 or higher non-hematological toxicity from the proposed over-exposure to CGRP antagonist. The combination was well tolerated without any need for therapy discontinuation or dose modifications. Conclusions: It is recommended to follow the manufacturers' guidance on drug interactions, however, in the setting where there are no other options, concomitant use of CGRP antagonists with azole antifungals is possible with monitoring and observation for adverse effects. [ABSTRACT FROM AUTHOR]

Concurrent tuberculosis and fungal otitis media complicated with skull base osteomyelitis is a rare and intricate clinical entity, particularly in well-controlled diabetes mellitus patients with unusual symptomatology. We present the case of an elderly gentleman with well-controlled type II diabetes mellitus who endured four months of chronic left ear pain, left-sided temporal headaches, and left ear pulsatile tinnitus, which persisted despite multiple courses of antibiotics. Initial investigations yielded conflicting suggestions, indicating the possibility of either an infection or the presence of a glomus tumor. However, intraoperative samples sent for microbiological and histological investigation revealed the presence of Aspergillus Niger and Mycobacterium complex. Treatment with antifungal and antituberculosis agents led to a remarkable improvement in the patient's clinical symptoms and radiological and biochemical markers. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is included in the World Health Organization fungal priority pathogen list, complied to expedite improved research and public-health interventions. The limited number of available antifungal drugs, their associated toxicity, and the emergence of drug-resistant strains make the development of new therapeutic strategies mandatory. Pattern-recognition receptors (PRRs) from the host's innate immune system constitute a potential source of new antimicrobial agents. CD5 and CD6 are lymphoid members of the ancient scavenger receptor cysteine-rich superfamily (SRCR-SF) which bind pathogen-associated molecular patterns (PAMPs) of fungal and bacterial origin. Evidence supports the concept that such binding maps to 11-mer sequences present in each of their three SRCR extracellular domains. Herein, we have designed synthetic peptides containing tandems of such 11-mer sequences (namely CD5-T and CD6-T) and analyzed their C. neoformans-binding properties in vitro. Our results show both inhibitory effects on fungal growth and an ability to impact capsule formation and titanization, two critical virulence factors of C. neoformans involved in immune evasion. These effects hold promise for CD5-T and CD6-T peptides as single or adjuvant therapeutic agents against cryptococcosis. [ABSTRACT FROM AUTHOR]

Pyodermatitis-pyostomatitis vegetans (PD-PSV) is a rarely described benign inflammatory skin disease of unknown etiology. It is often associated with chronic inflammatory bowel disease. It is common in young and middle-aged individuals, yet rarely in children. Herein, we report the case of a young child who had developed pustular lesions on the skin and mouth as a manifestation of PD-PSV with manifestations associated with primary immune deficiency (PID). Treatment with immunoglobulins and antimycotics resulted in the resolution of the cutaneous and mucosal lesions. To our knowledge, the association between PD-PSV and DIP has not been previously reported. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Fungal endocarditis is a rare but potentially fatal infection with significant diagnostic and management challenges. Antifungal therapy and surgical debridement are the preferred treatments in these cases. Antimicrobial therapy with multiple antifungal agents may be required in high‐risk patients presenting with prolonged fever suspected of having fungal endocarditis. Recurrent fungal endocarditis, particularly involving Candida parapsilosis, is a rare and challenging clinical entity with limited management guidelines. We present the case of a 44‐year‐old female with a history of intravenous drug use and treatment‐resistant chronic hepatitis C who developed recurrent Candida parapsilosis endocarditis. Initially, she presented with native aortic valve fungal endocarditis, which was managed with antifungal therapy and surgical aortic valve replacement. Despite this intervention, she experienced a subsequent episode of prosthetic valve Candida parapsilosis endocarditis, further complicated by prolonged fungemia. This case underscores the complexities of managing recurrent fungal endocarditis and highlights the need for ongoing research to refine treatment strategies for this challenging condition. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Chromoblastomycosis, though rare in non‐endemic regions like Lebanon, should be considered in patients presenting with chronic, verrucous skin lesions unresponsive to conventional therapies. Multimodal treatment combining oral antifungals, cryotherapy, and adjunctive topical 5‐Fluorouracil demonstrates efficacy in managing refractory cases. Follow‐up visits three and 6 months after treatment cessation showed sustained lesion clearance and no recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Recalcitrant dermatophytosis is an emerging phenomenon that occurs worldwide, and Trichophyton indotineae is currently the prominent cause. Materials and methods: Skin specimens from patients with tinea infection were obtained by scrubbing and then sectioned into three fragments. Two fragments were subjected to direct microscopic examination and culture, while the third portion was utilized in the PCR method. Results: Isolates were morphologically identified as Trichophyton mentagrophytes/interdigitale complex (n = 60 [83.33%]), Microsporum canis (n = 8 [11.11%]), Trichophyton rubrum (n = 3 [4.16%]), and Epidermophyton floccosum (n = 1 [1.38%]). Among 60 T. mentagrophytes complex isolates, 53 (88.33%) were classified as T. indotineae and seven as T. interdigitale genotype II. The disease duration was longer in the T. indotineae group (P = 0.035). Both Gradient PCR and skin‐sampling methods yield similar results in terms of positive and negative cases (P = 1.0000). The time patients stopped their medication did not impact the positive case numbers (P = 0.803). Gender had no effects on the frequency (P = 0.699). Familial contamination, dermatologic disorder, and other underlying conditions did not differ in the two group infections (P > 0.05). Steroid usage is strongly associated with the emergence of tinea infection (P < 0.04). The duration of antifungal administration had a substantial effect on the emergence of resistant organisms (P = 0.05). Conclusions: Steroid usage, T. indotineae involvement, and prolonged exposure to antifungals were the solid and influential factors in recalcitrant involvement. Regarding quick and suitable diagnosis and treatment, which is essential in preventing recalcitrant cases, we suggest that direct skin sample PCR can meet the demands. [ABSTRACT FROM AUTHOR]

Background: Oxiconazole nitrate is a broad spectrum imidazole antifungal agent. Poor solubility of this drug caused low bioavailability that limits the antifungal efficiency. Due to their low efficiency as drug delivery many conventional dosage form such as cream and ointment need high concentration of active ingredient for effective therapy, which may cause side effect. Materials and Methods: In this study nanosponge was prepared using hydroxyl ethyl cellulose and poly vinyl alcohol by emulsion solvent diffusion method. The entrapment efficiency of particle size has found in the range of 100nm-1µm and 55% - 88% respectively. Based on the characterization, nanosponge with least particle size and highest entrapment efficiency was selected for gel formulation. Results and Discussion: Four different formulations of gel were prepared by using carbopol 934 with varying the concentration of penetration enhancer and various evaluation studies were carried out. The in vitro release study showed that the nanosponge loaded gel formulation with higher concentration of penetration enhancer showed greater drug release. Conclusion: while compared with conventional gel. Based on the stability study carried out, it was concluded that formulation was stable at ambient conditions. [ABSTRACT FROM AUTHOR]

Antifungal substances are essential for managing fungal infections in humans, animals, and plants, and their usage has significantly increased due to the global rise in fungal infections. However, the extensive application of antifungal agents in pharmaceuticals, personal care products, and agriculture has led to their widespread environmental dissemination through various pathways, such as excretion, improper disposal, and agricultural runoff. Despite advances in wastewater treatment, many antifungal compounds persist in the environment, affecting non-target organisms and contributing to resistance development. This study investigates the environmental impact of two novel antifungal agents, VT-1161 and T-2307, recently introduced as alternatives for treating resistant Candida spp. We assessed their ecotoxicity and mutagenicity using multiple bioassays: immobilization of Daphnia magna, growth inhibition of Raphidocelis subcapitata, luminescence inhibition of Aliivibrio fischeri, and mutagenicity on Salmonella typhimurium strain TA100. Results indicate that both VT-1161 and T-2307 exhibit lower toxicity compared to existing antifungal compounds, with effective concentrations (EC50) causing 50% response ranging from 14.34 to 27.92 mg L−1. Furthermore, both agents were classified as less hazardous based on the Globally Harmonized System of Classification and Labeling of Chemicals. Despite these favorable results, further research is needed to understand their environmental behavior, interactions, and potential resistance development among non-target species. Our findings highlight the importance of comprehensive environmental risk assessments to ensure the sustainable use of new antifungal agents. [ABSTRACT FROM AUTHOR]

Background New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non- Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data. Objectives Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital. Materials and methods Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific). Results A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25–0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n  = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4–>8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species. Conclusions Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus , L. prolificans , Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava. [ABSTRACT FROM AUTHOR]

In this age of emergent resistance to antimicrobial agents, pathogenic fungi are not an exception. Diverse strategies have been implemented to curb rampant fungal infections including screening new drugs and stewardship programs. A plethora of recent studies have proved that phytochemicals are efficacious against pathogenic fungi and have potent antifungal activity. This review examines the use of phytochemicals as possible alternative antifungal agents against dermatophytes particularly Trichophyton spp. Literature search was done using three search engines namely Google Scholar, PubMed and Science Direct limited to the year 2019–2023 only. A total of 30 articles were included and 48 plant extracts were evaluated. The major phytochemicals that proved to be potent antifungals both in vitro and in vivo were terpenoids and phenolics. The antifungal potential of phyto-compounds was significantly elevated by incarnation with nanotechnology. Although much has been done in screening of herbal extracts as possible antifungal agents huge gaps still exist on full characterization of all active herbal extracts with antifungal potential especially against resistant strains, together with their mechanism of action, formulation of pharmaceutical dosage forms and clinical trials. [ABSTRACT FROM AUTHOR]

Candidemia is emerging as a significant concern in children, particularly among those with underlying conditions like malignancies or prematurity. The interpretation of epidemiological data on candidemias and their antifungal resistance plays a vital role in aiding diagnosis and guiding clinicians in treatment decisions. From 2014 to 2021, a retrospective analysis was conducted in İstanbul, Turkey; comparing Candida albicans and non-albicans (NAC) spp in both surviving and deceased groups. Furthermore, an examination of Candida parapsilosis and other species was performed, assessing various clinical and laboratory parameters. Among 93 patients, with a median age of 17 months, C. parapsilosis emerged as the predominant isolated species (44%), followed by C. albicans (34.4%). Resistance to fluconazole, voricanozole, and echinocandins, along with a history of broad-spectrum antibiotic use were found to be significantly higher in the non-albicans Candida group compared to C. albicans group. In the C. parapsilosis group, statistically lower age was identified in comparison to the other groups (P  = .018). In addition, high fluconazole and voriconazole resistance was detected in Candida parapsilosis spp. Our study highlights a notable prevalence of C. parapsilosis, particularly in younger children, which is different from similar studies in childhood. This trend may be attributed to the common use of total parenteral nutrition and central venous catheter in gastrointestinal disorders and metabolic diseases. Furthermore, as anticipated, high azole resistance is noted in C. parapsilosis and other non-albicans Candida species. Interestingly, resistance to both amphotericin B and echinocandins within this group has been notably high. It is crucial to emphasize the considerable antifungal resistance seen in C. parapsilosis isolates. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the feasibility of capturing antimicrobial usage data from prisons for inclusion in the Antimicrobial Use and Resistance in Australia (AURA) surveillance system and to analyse 2021 and 2022 South Australian (SA) usage data for notable trends. Methods: Monthly antimicrobial supply data for eight SA prisons were collected. Antimicrobial volume was converted into the World Health Organization metric, defined daily doses (DDD). Usage rates were calculated relative to prison occupied bed days (OBD). Results: Annual usage of systemic antimicrobials across eight SA prisons totalled 26,448 DDD and 23,526 DDD in 2021 and 2022 respectively. Antibacterials accounted for 80.6% of all antimicrobials dispensed during the study period. The average antibacterial usage rate in female prisons was higher on average than in male prisons. The state-wide systemic antibacterial usage rate in SA prisons declined by 11.3% from 23.8 DDDs/1000 OBD in 2021 to 21.1 DDDs/1000 OBD. Doxycycline, amoxicillin, flucloxacillin, amoxicillin-clavulanic acid, and cefalexin accounted for 72% of the total systemic antibacterial usage rate. Variation in the oral and topical antifungal agents used and the rate of use was observed between prisons. Conclusions: This SA pilot study demonstrates the feasibility of including prisons in routine national antimicrobial surveillance using similar methodology to hospital surveillance. The contributing facilities comprised 6.1% of all Australian prison beds, and extrapolation of the results suggests that the identified gap in surveillance may equate to over 400,000 DDD per annum in prisons nationwide, equating to approximately 5% of hospital inpatient antimicrobial usage. What is known about the topic? Surveillance of antimicrobial use is a useful tool to identify overuse or inappropriate use and enable targeted interventions to optimise antimicrobial prescribing and reduce the risk of antimicrobial resistance. What does this paper add? The methodology currently used to monitor antimicrobial use in Australian hospitals could be utilised to conduct facility-level surveillance in Australian prisons and would provide a mechanism to benchmark use between facilities and identify unexpected or inappropriate use. What are the implications for practitioners? Surveillance of antimicrobial use in prisons would support prison healthcare workers to monitor use over time, identify any increasing or unexpected trends in use, and target educational interventions to ensure compliance with antimicrobial prescribing guidelines. [ABSTRACT FROM AUTHOR]

The article focuses on terra firma-forme dermatosis (TFFD), a benign and often unrecognized skin condition in children characterized by brown-grayish patches that resemble dirt. Topics include the common occurrence of skin disorders in pediatric exams, the presentation and distribution of TFFD, and the unknown pathogenesis and clinical features of this condition.

We herein report the synthesis, spectral analysis, DFT calculations, in vitro and in silico biological activities of novel N'-((2-thioxo-1,2-dihydroquinolin-3 yl)methylene)isonicotinohydr-azide with its Cu(II), Co(II), Ni(II), and Zn(II) complexes have been successfully prepared. The ligand and the complexes were characterized by analytical, FT-IR, 1H NMR, mass, UV–visible spectroscopy, molar conductivity, and magnetic susceptibility measurements. Density Functional Theory (DFT) estimations for the ligand at the DFT/B3LYP level via 6-31 G++ (d, p) replicate the structure and geometry. Furthermore, molecular docking and ADME calculations were also performed to correlate and interpret the experimental results. The antimicrobial activity study illustrated enhancement in the activity of the free ligand upon complex formation, and the Cu(II) complex (MIC 25 µg mL−1) may be considered a promising antibacterial agent, and Ni(II) and Zn(II) complexes (MIC 25 µg mL−1) as promising antifungal agent. Also, synthesized Ni(II) and Zn(II) metal complexes (MIC 3.125 µg mL−1) showed promising anti-TB activity against Mycobacterium tuberculosis. In the antioxidant activity, the Cu(II) complex showed excellent activity as compared to standard drugs and in silico docking studies were carried out against Cytochrome c Peroxidase (PDB ID: 2X08). [ABSTRACT FROM AUTHOR]

The DMSO/I2 mediated cyclization reaction of (E)-3-(3,4-dimethoxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one afforded the 2-(3,4-dimethoxyphenyl)-4H-chromen-4-one (DMPC). DMPC was characterized by FT-IR, 1H NMR, 13C NMR and HRMS techniques. DMPC was screened for their in vitro antibacterial activity against four bacterial strains namely E. coli, B. subtilis, S. aureus, and Streptococcus spp. and antifungal activity against R. oryzae, P. chrysogenum, A. niger, and C. albicans fungal strains. The synthesized compounds exhibited significant antibacterial and antifungal properties. DMPC possesed potent antibacterial activity against Streptococcus spp. while the powerful antifungal action was found against P. chrysogenum. Besides % free radical scavenging activity was accessed using DPPH and OH assays. DMPC was found to be more active DPPH radical scavenger than OH radical. Theoretical investigation of DMPC was carried out by density functional theory (DFT) method at the B3LYP/6-311++G(d,p) level of theory. Computational investigation of molecular structure, MESP, and HOMO–LUMO was performed to study DMPC. The calculated energy gap of FMOs was found to be 4.25 eV for DMPC. In the MESP plot, the most electronegative potential region found around the oxygen atom. The theoretical and experimental NMR was correlated and correct NMR assignments have been made. Based on the physicochemical features, lipophilicity, water solubility, pharmacokinetic characteristics, and drug similarity matching investigations, the DMPC was revealed to have favorable biological qualities. Highlights: DMSO/I2 mediated cyclization reaction of (E)-3-(3,4-dimethoxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one afforded the 2-(3,4-dimethoxyphenyl)-4H-chromen-4-one (DMPC). DMPC was screened for its in vitro antibacterial activity against four bacterial strains namely E. coli, B. subtilis, S. aureus, and Streptococcus spp. Antifungal activity of DMPC against R. oryzae, P. chrysogenum, A. niger, and C. albicans fungal strains. DMPC exhibited significant antibacterial and antifungal properties. Computational study on MESP, HOMO–LUMO, NMR, and IR. ADME study indicates good pharmacological profile. [ABSTRACT FROM AUTHOR]

Purpose: To report a patient with bilateral scleritis who was initially treated for infectious scleritis, and subsequently diagnosed as granulomatosis with polyangiitis (GPA). Method: Retrospective chart review. Result: A 48-year-old female with a known history of diabetes presented with pain, redness, and blurring of vision in the right eye. She was diagnosed as scleritis with retinal detachment and underwent vitrectomy, with silicone oil tamponade and intravitreal injections of antibiotics, and antifungal agents. She presented with active scleritis with additional multiple pus points. Several scleral biopsies failed to yield any microorganism and finally, the painful blind eye was enucleated. The enucleated specimen grew gram-positive bacteria which were identified as Staphylococcus arlettae by polymerase chain reaction (PCR)-based sequencing of the 16S rRNA gene. Nine months after the onset of symptoms in the right eye, the patient developed necrotizing scleritis in the left eye. Laboratory investigation revealed a positive cytoplasmic- anti-neutrophil cytoplasmic autoantibody, which was previously negative during the right eye involvement. She was diagnosed with GPA by a rheumatologist and treated accordingly. Conclusion: Retinal detachment may be associated with scleritis, and ANCA testing may not detect GPA in its early stages. Once infection has been excluded, clinicians should not be afraid to use high-dose immunosuppression instead of surgery to treat retinal detachment associated with scleritis. [ABSTRACT FROM AUTHOR]

This work summarizes the application of gas fumigation technology in postharvest fruit quality management and related biochemical mechanisms in recent years. Gas fumigants mainly include SO2, ClO2, ozone, NO, CO, 1-MCP, essential oils, H2S and ethanol. This work indicated that gas fumigation preservatives can effectively improve postharvest fruit quality, which is mainly manifested in delaying senescence, inhibiting browning, controlling disease and alleviating chilling injury. Gas preservatives are mainly involved in postharvest fruit quality control in the roles of antifungal agent, anti-browning agent, redox agent, ethylene inhibitors, elicitor and pesticide remover. Different gas preservatives have different roles, but most of them have multiple roles at the same time in postharvest fruit quality management. In addition, the role of some gas preservatives with direct antifungal activity in the control of postharvest fruit diseases can also activate defense systems to improve fruit resistance. It should be noted that some gas fumigation treatments with slow-release effects have been developed recently, which may allow gas fumigation gases to perform better. Moreover, some gas fumigants can cause irrational side effects on the fruit and some combined treatments need to be found to counteract such side effects. [ABSTRACT FROM AUTHOR]

• The study explores antifungal activity of leaf extract of Chenopodium album var. album L. • The ethyl acetate extract of C. album showed excellent antifungal activity against Candida strains • Fraction 2, isolated via column chromatography, exhibited potent antifungal activity against pathogenic Candida strains. • The chemical characterization of F2 fraction were evaluated through GC–MS Chenopodium album var. album L., renowned as lamb's quarters, is a versatile medicinal plant, revealing its efficacy in treating various ailments. This study evaluated the in vitro antifungal activity of ethyl acetate extract of C. album var. album L. Chenopodium album leaf extract demonstrated antifungal potential via the Agar well-diffusion and Broth-dilution method. Active fractions, obtained through column chromatography, were rigorously tested against Candida spp. The most potent fraction underwent detailed analysis with High-Performance Thin-Layer Chromatography (HPTLC), Gas Chromatography Mass Spectrometry (GC–MS), and Fourier-Transform Infrared Spectroscopy (FT-IR), for comprehensive characterization. The ethyl acetate extract (EAE) exhibited significant antifungal activity, with Candida albicans being the most susceptible (inhibition zone of 14.67 ± 0.58a). Fractionation of the EAE yielded a highly active F2 fraction, which showed a remarkable zone of inhibition against C. albicans (17.50 ± 1.00a). Comprehensive examinations, including HPTLC, GC–MS, and FT-IR, identified 12 compounds in the F2 fraction, and the major compounds were Furo [2,3- c ] pyridine, 2,3-dihydro-2,7-dimethyl, Bis (2-ethylhexyl) phthalate, and 2,3,4,4-Tretrapropyl-1-(trimethylsilyl)-1-(trimethylsilyloxy)-1,3-diaza-2,4-diborabutane. This study marks the first report of these 12 compounds identified from the F2 fraction of C. album. The present study highlights the antifungal activity of EAE and its fractions from C. album var. album that could be further explored for the selection of leads that may contribute to novel drug development. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a major health threat with high morbidity and mortality, highlighting the urgent need for rapid diagnostic tools to detect antifungal resistance. Traditional culture-based antifungal susceptibility testing (AFST) methods often fall short due to their lengthy process. In our previous research, we developed a whole-slide imaging (WSI) technique for the high-throughput assessment of bacterial antibiotic resistance. Building on this foundation, this study expands the application of WSI by adapting it for rapid AFST through high-throughput monitoring of the growth of hundreds of individual fungi. Due to the distinct "budding" growth patterns of fungi, we developed a unique approach that utilizes specific cell number change to determine fungi replication, instead of cell area change used for bacteria in our previous study, to accurately determine the growth rates of individual fungal cells. This method not only accelerates the determination of antifungal resistance by directly observing individual fungal cell growth, but also yields accurate results. Employing Candida albicans as a representative model organism, reliable minimum inhibitory concentration (MIC) of fluconazole inhibiting 100% cells of Candida albicans (denoted as MIC100) was obtained within 3h using the developed method, while the modified broth dilution method required 72h for the similar reliable result. In addition, our approach was effectively utilized to test blood culture samples directly, eliminating the need to separate the fungi from whole blood samples spiked with Candida albicans. These features indicate the developed method holds great potential serving as a general tool in rapid antifungal susceptibility testing and MIC determination. [ABSTRACT FROM AUTHOR]

Copyright of Duzce University Journal of Science & Technology is the property of Duzce University Journal of Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 μg ml−1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy. LAY SUMMARY: Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial consumption (AMC) data in Latin America are scarce and usually spread out across different sources used to make AMC calculations, making it difficult to both standardize and compare regions through similar time frames. The main objective was to analyze AMC trends in Social Security tertiary care hospitals in Costa Rica in the period spanning January 2017 to December 2021, using both the defined daily dose (DDD)/100 bed days and DDD/100 discharges. Methods: This is a retrospective observational study of antimicrobial consumption. Global consumption trends were calculated and expressed as DDD/100 bed days and DDD/100 discharges. Trends in antimicrobial consumption were analyzed using a simple linear regression model to determine potential differences in antimicrobial usage throughout the study's duration. Results: A statistically significant increase in the consumption expressed in DDD/100 discharges was observed in the following groups: carbapenems, 7.6% (trend: 64.68, p < 0.0001), trimethoprim-sulfamethoxazole: 12.6% (trend: 16.45, p < 0.0001), quinolones 9.4% (trend: 36.80, p = 0.02), vancomycin 2.0% (trend: 16.30, p = 0.03), echinocandins: 6.0% (trend: 15.17, p = 0.01) and azole antifungals: 12.10% (trend: 102.05, p < 0.0001). Additionally, a statistically significant increase of 10.30% in the consumption of azole antifungals expressed in DDD/100 bed days was observed (p = 0.0008). In contrast, a statistically significant decrease in consumption, expressed in DDD/100 discharges, was identified for cephalosporins −6.0% (p < 0.0001) and macrolides −16.5% (p < 0.0001). Macrolides also showed a downward trend in consumption, as expressed in DDD/100 bed days (−14.3%, p < 0.0001). According to World Health Organization (WHO) access, watch and reserve (AWaRe) classification trend analysis, only the reserve group showed a statistically significant upward change of 9.2% (p = 0.016). Conclusions: This five-year analysis demonstrated trends over time in overall antimicrobial consumption measured in DDD/100 bed days and DDD/100 discharge rates that correlate. In general, for all antimicrobials, after the implementation of antimicrobial stewardship programs (ASP), a downward trend is reported; in contrast, during the COVID-19 pandemic the AMC shows a general upward trend. The comparison between DDD/100 bed days and DDD/100 discharges allows for complementary comparisons to be made regarding antimicrobial exposure in a clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. Methods: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. Results: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. Conclusion: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). Methods: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. Results: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. Conclusions: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. Chinadrugtrials.org.cn registry number: CTR20220918. [ABSTRACT FROM AUTHOR]

Purpose: Candidemia is associated with high mortality especially in critically ill patients. Our aim was to identify predictors of mortality among critically ill patients with candidemia with a focus on early interventions that can improve prognosis. Methods: Multicenter retrospective study. Setting: This retrospective study was conducted in Intensive Care Units from three European university hospitals from 2015 to 2021. Adult patients with at least one positive blood culture for Candida spp. were included. Patients who did not require source control were excluded. Primary outcome was 14-day mortality. Results: A total of 409 episodes of candidemia were included. Most candidemias were catheter related (173; 41%), followed by unknown origin (170; 40%). Septic shock developed in 43% episodes. Overall, 14-day mortality rate was 29%. In Cox proportional hazards regression model, septic shock (P 0.001; HR 2.20, CI 1.38–3.50), SOFA score ≥ 10 points (P 0.008; HR 1.83, CI 1.18–2.86), and prior SARS-CoV-2 infection (P 0.003; HR 1.87, CI 1.23–2.85) were associated with 14-day mortality, while combined early appropriate antifungal treatment and source control (P < 0.001; HR 0.15, CI 0.08–0.28), and early source control without appropriate antifungal treatment (P < 0.001; HR 0.23, CI 0.12–0.47) were associated with better survival compared to those without neither early appropriate antifungal treatment nor source control. Conclusion: Early source control was associated with better outcome among candidemic critically ill patients. [ABSTRACT FROM AUTHOR]

This work investigates the potential of using Callistemon citrinu flower extract, commonly known as bottlebrush, in the environmentally friendly synthesis of Rhodium nanoparticles (Rh NPs). Callistemon citrinu flower extract contains a high concentration of flavonoids and other phytochemicals. Hence, the extract was used to provide the essential components for an environmentally, sustainable synthesis method of Rh NPs. Different characterization analyses were used to evaluate the different properties of the synthesized particles. UV spectroscopy analysis demonstrated a continuous UV absorption spectrum attributed to the formation of Rh NPs. The XRD data and SAED analysis showed an amorphous nature of the synthesized Rh NPs. The HRTEM imaging provided morphological information about the Rh NPs tested sample, where the efficiency of Callistemon citrinu flower extract as a capping agent was reported. Furthermore, Raman spectra displayed the characteristic vibrational bands of the synthesized Rh NPs. The antimicrobial activity of the synthesized samples was tested against several dental pathogens, that play a role in dental caries, Staphylococcus aureus (SA), Bacillus subtilis (BS), Candida albicans (CA), Escherichia coli (Eco), and Staphylococcus epidermidis (S. Epi). In comparison with the control, Chlorhexidine (CHX), Rh NPs showed a greater impact on C. albicans (20 ≤ Zone of inhibition (ZOI) (mm) ≤ 26). The statistical analysis demonstrated that Rh NPs had a greater mean ZOI than the Callistemon citrinu flower extract. These results reveal the considerable potential and biological capacity Rh NPs have as an antifungal agent for dental applications. [ABSTRACT FROM AUTHOR]

Leonotis nepetifolia (L.) R. Br. (Lamiaceae) is a naturalised medicinal plant in Brazil known as 'cordão-de-frade', being used in folk medicine for the treatment of a variety of conditions such as infections and inflammations. L. nepetifolia leaf and flower essential oils were isolated by hydrodistillation, and their compounds were identified by GC-MS analysis. The leaf essential oil major constituents were germacrene D (31.5%), and β-caryophyllene (19.2%), while in flower essential oil the main constituents were β-elemene (31.2%), and germacrene D (12.1%). The essential oils were investigated against a broad spectrum of bacteria and fungi using the microdilution method, exhibiting MIC50 values of 3.93–250 µg mL−1. Both oils showed excellent antifungal properties, which is a very important finding since most fungi have shown increased resistance to known antifungal agents. According to these results, the essential oils of L. nepetifolia are promising sources of new antimicrobial agents, especially for yeast. [ABSTRACT FROM AUTHOR]

Recent reports of P. olsonii causing postharvest rot of cherry tomatoes emphasize the need for effective strategies to prolong fruit shelf life. This study is the first to explore the use of essential oils (EOs), recognized for their antimicrobial properties, as a potential method to prevent postharvest losses from P. olsonii. Antifungal activity was tested for ten EOs at a concentration of 625 μL/L using the vapor diffusion method. Thyme, wild thyme, savory, oregano, and marjoram completely inhibited fungal growth over 14 days. Thyme EO, at a minimum inhibitory concentration (MIC) of 250 μL/L, fully inhibited all strains, while oregano, wild thyme, and savory were effective at 500 μL/L. Marjoram EO showed weaker activity. The lowest IC90 values, ranging from 35.72 to 162.72 μL/L, were estimated for thyme and oregano. In cherry tomatoes, oregano EO completely halted P. olsonii growth at 250 μL/L; thyme was effective for seven days; wild thyme and savory for two days. Thyme EO prevented P. olsonii spore germination at 500 μL/L for seven days, though germination occurred at half that concentration. The IC90 values varied between 256.2 and 138.7 μL/L depending on the strain. The vapor phase of EOs at 125 μL/L influenced the sensory characteristics of cherry tomatoes; however, for thyme and oregano, this effect was not negative due to their culinary association with tomato flavor. The selected EOs could be used to control and prevent postharvest fruit losses, but further research is needed to optimize their application. [ABSTRACT FROM AUTHOR]

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-β-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance, and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the antifungal activity of different drugs and preparations. The current findings demonstrated that the drugs and medicinal plant extracts that were examined for antifungal properties against various species. These species demonstrated antifungal activity almost on par with the commercial fungicide used as a positive control, even at low dosages. For further of the bioactive substances causing the noted antifungal activity, more research is required. Natural fungicides generated from plants could provide new active molecules, especially those with antifungal properties. The high percentage of active extracts in the species under investigation, which were chosen based on known ethnobotanical data, supports the applicability of this method for choosing plant species when looking for a certain activity. [ABSTRACT FROM AUTHOR]

The study's objective was to assess the antifungal efficacy of various medications and formulations. Medicinal plant extracts and medications that were tested for antifungal qualities against different species were shown to have antifungal capabilities. Even at modest dosages, these species showed antifungal activity that was nearly identical to that of the commercial fungicide used as a positive control. More research is needed to determine which bioactive compounds are responsible for the observed antifungal action. Plant-based natural fungicides may yield novel active compounds, particularly those with antifungal qualities. The relevance of this strategy for selecting plant species when seeking a certain activity is supported by the high percentage of active extracts in the species under inquiry, which were selected based on established ethnobotanical data. [ABSTRACT FROM AUTHOR]

Fungal infections present significant clinical challenges due to their diverse types and the increasing incidence of drug-resistant strains. Traditional antifungal treatments often encounter issues with penetration, efficacy and patient compliance. The study involves a comprehensive review of the structure and mechanism of transfersomes, their advantages over conventional and other nano carriers, and the integration of herbal extracts. Key aspects include improved skin penetration, enhanced bioavailability of herbal actives, and targeted delivery to infected areas. Transfersomes demonstrate significant benefits in antifungal therapy, including higher efficacy, faster symptom relief, reduced side effects and improved patient compliance. The enhanced penetration and stability of transfersomes facilitate a more effective delivery of herbal actives, making them a superior choice for topical treatments. The study also identifies areas for future research, such as optimizing formulation processes and exploring combination therapies to maximize therapeutic outcomes. Transfersomes represent a transformative advancement in the field of topical drug delivery. Their integration with herbal medicines offers a promising approach to addressing fungal infections more effectively. Future research should focus on clinical validation and further refinement of transfersome-based formulations to fully realize their potential in enhancing the management of fungal infections and other dermatological conditions. [ABSTRACT FROM AUTHOR]

A lot of people use emulsion gels because they are easier to use than creams and ointments and because they release drugs faster and more thoroughly. The study's goals were to develop and clarify an antifungal emulgel that can be put on the skin. In the Miconazole Emulgel method, the gelling agent, carbopol 934 is used with great accuracy. For the water phase, Tween 20 is an emulsifier. Propylene glycol is a co-surfactant. Methyl and propyl paraben are preservatives. And liquid paraffin is the oil in the oil phase mixture. Triethanolamine is used to bring the pH of the emulgel to between 6 and 6.4. Miconazole, which is like cholesterol for fungi, stops fungi from growing by decreasing ergosterol production, which makes membranes more mobile. There were no signs of phase separation in the improved F6 formulation. The improved mix had better drug content, spreadability, extrudability and viscosity. A 14-17 mm zone of blockage showed that the antifungal worked against Candida albicans and the drug released in vitro was 97.45%. All of the items had a pH level between 6 and 6.4, which means they were safe for the skin. The results show that the topical Miconazole Emulgel with Carbopol 934 is very smooth, easy to apply and calming. [ABSTRACT FROM AUTHOR]

Candida species are opportunistic fungal pathogens commonly found in clinical settings, causing a spectrum of infections known as candidiasis. The virulence of these organisms is multifunctional, involving attributes such as adhesion, biofilm formation, secretion of hydrolytic enzymes and evasion of host immune responses. Evaluating the Candida albicans and non-albicans Candida species isolated in different clinical samples and their in vitro antifungal susceptibity profile. This was a 1 years prospective observational study conducted in the Department of Microbiology at Integral Institute of Medical Sciences & Research, Lucknow. The sample size of this study was 1130. Culture identification, specification, antifungal susceptibility testing was conducted in Microbiology Department according to the CLSI guidelines. Out of 1130 different samples, 67.5% (652) were culture positive, among them only 21.1% (138) were Candida isolates. Out of which 53(38.4%) were Candida albicans, while 85(61.6%) were Non-Candida albicans. Among Non-Candida albicans, the frequency of Candida tropicalis was 58 (68.2%). Maximum number of Non-Candida albicans were isolated from Urine samples (44.7%) followed by Vaginal swab(22.3%) and sputum(20%) While frequency of C.albicans was found more in Sputum sample (39.6%), followed by urine (24.5%), Vaginal swab (22.6%). It was observed that 112(53.5%) Candida isolates shows biofilm production, While Phospholipidase enzymes production were observed in only 21(10.04%) of Candida isolates. It was observed that the maximum sensitivity was observed in Amphotericin-B(95%), followed by Voriconazole(85%) and itraconazole(49.2%). In conclusion, characterization of virulence factors in Candida species isolated from various clinical specimens provides valuable insights into the pathogenesis and clinical outcomes of candidiasis. Continued research efforts are essential to address the evolving challenges posed by Candida infections and improve patient outcomes in clinical practice. [ABSTRACT FROM AUTHOR]

There are several benefits to use topical treatments for fungal infections, such as being able to target the infection directly and lowering the risk of widespread side effects. Antifungal drugs must get through the top layer of skin, when they are applied to the skin in order to work at their best. An antifungal drug called chlorphenesin was used to help it spread more quickly and stop the fungal growth. By using the above mentioned drug the cream formulation was prepared and optimised. The all of prepared formulation batches were analysed, and all of them were passed as per the requirements. The results of all tests showed that the cream can be used on the face to protect against fungal diseases. The study's results clearly shows that the prepared formulations having the antifungal activity on the various fungi studied in this study. [ABSTRACT FROM AUTHOR]

Many of the existing antimicrobial agents are showing ineffectiveness against the pathogenic microbes due to the resistance of microbes towards them. But apart from the synthetic drugs, many herbs are found to be effective in the inhibition of these microbes and serve as potent anti-microbial agents. In this study, the methanolic extract of Grewia asiatica leaves was evaluated against the fungus i.e., Candida albicans and Trichophyton rubrum. The extract used to compare with the standard drug i.e., Amphoterecin. The extract at the concentration of 62.5µg/well showed the lowest inhibition and on increasing the concentration of extraction inhibition zone increased and the constant zone of inhibition found from 125-1000 µg/well in case of Candida albicans. The leaf extract of Grewia asiatica also showed the inhibition of the fungus Trichophyton rubrum. On increasing the extract concentration, the zone of inhibition also increased. The maximum inhibition showed in concentration of 1000 µg/well. [ABSTRACT FROM AUTHOR]

The plant-pathogenic fungi cause great losses to agricultural crops and thus threaten food resources all over the world. These pathogens cause numerous diseases in fruits, vegetables, cereals and other important crops. Currently, a vast number of chemical and biological methods are used to control these diseases. Biological control in a combination of several modes of action is effective in controlling the diseases. Four most frequently used ethnomedicinal plants of family Zingiberaceae were selected for estimation of essential oils (EOs) and antifungal evaluation. The hydrodistillation method, using Clevenger's apparatus was used for extraction of the volatile constituents/essential oil. Further, the oil per cent (%) yield extracted from Curcuma longa was 0.73%, 0.89% from Zingiber officinale, 1.93% from Alpinia galanga, whereas it was highest in case of Elettaria cardamomum (3.66%). Furthermore, all EOs were investigated for their antifungal activity against four pathogenic fungi named as F. oxysporum, F. proliferatum, A. niger and A. flavus by using Disc Diffusion method. Inhibitions of fungal growth were measured in form of zone of Inhibition. The efficacy of the oil of C. longa showed the highest zone of inhibition against A. niger (18.8±1.27). The efficacy of the oil of Z. officinale recorded highest zone of inhibition at pure concentration against F. proliferatum (16.7±0.62). A. galanga showed the highest zone of inhibition F. oxysporum (18.7±1.00). E. cardamomum found effective against A. niger (16.8±0.05). The present finding shows the better potency against all tested fungal pathogens; therefore, antifungal drugs could be developed through these plants essential oils in future after detailed in-vivo and in-silico investigation. [ABSTRACT FROM AUTHOR]

The rise of Candida auris as a multidrug-resistant pathogen presents considerable challenges in the clinical environment, requiring the identification of new therapeutic targets. This study aimed to annotate a hypothetical gene product, Set5 (Su(var)3-9, Enhancer-of-zeste, Trithorax) lysine methyltransferase, in Candida auris using sequence and structure analysis. Utilizing advanced bioinformatics tools, including sequence alignment, phylogenetic analysis and structural modeling, we sought to provide a thorough annotation of this gene product. Our methodology involved identifying conserved motifs characteristic of SET and MYND (myeloid translocation protein, Nervy, Deaf, SMYD) methyltransferases and confirming the key catalytic and substrate-binding domains through structural modeling. The results showed significant sequence and structural similarities with known SMYD family members, supporting the annotation of the hypothetical gene product as Set5 methyltransferase. This discovery not only enhances our understanding of Candida auris biology, but also identifies potential therapeutic targets for combating infections caused by this pathogen. The identification of SMYD in Candida auris could lead to new antifungal targets, contributing to global efforts to manage and treat infections caused by this challenging pathogen. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plant fungal diseases pose a significant threat to crop production. The extensive use of chemical pesticides has led to growing environmental safety risks and pesticide resistance of various plant pathogens. Therefore, it is an urgent task to explore novel eco‐friendly fungicidal agents with high efficacy to combat fungal infection. RESULTS: In this study, we rationally designed a series of novel thymol derivatives by incorporation of the sulfonamide moiety and evaluated their biological activities against plant pathogenic fungi. The bioassay results underscored the remarkable in vitro antifungal activity of compounds 5m and 5t against Phytophthora capsici (P. capsici), with EC50 values of 8.420 and 8.414 μg/mL, respectively. Their efficacies were superior to that of widely used commercial fungicides azoxystrobin (AZO, 20.649 μg/mL) and cabendazim (CAB, 251.625 μg/mL). Furthermore, compound 5v exhibited excellent in vitro antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum), with an EC50 value of 12.829 μg/mL, significantly outperforming AZO (63.629 μg/mL). In vivo bioassays demonstrated the impactful activity of compound 5v against S. sclerotiorum, achieving over 98% curative and protective efficacies at the concentration of 200 μg/mL. Further mechanistic investigations unveiled that compound 5v induced mycelial shrinkage and collapse in S. sclerotiorum, resulting in organelle damage and the accumulation of antioxidant enzyme activity. CONCLUSION: The significant antifungal efficacy of the prepared thymol derivatives shall encourage further exploration of compound 5v as a promising candidate to develop novel fungicides for crop protection. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]