UNASSIGNED: Candida albicans is an opportunistic pathogen that occurs as harmless commensals in the intestine, urogenital tract, and skin. It has been influenced by a variety of host conditions and has now evolved as a resistant strain. The aim of this study was thus detect the fluconazole resistant C. albicans from the root caries specimens and to computationally evaluate the interactions of an opaque-phase ABC transporter protein with the Psidium guajava bio-active compounds.
UNASSIGNED: 20 carious scrapings were collected from patients with root caries and processed for the isolation of C. albicans and was screened for fluconazole resistance. Genomic DNA was extracted and molecular characterization of Cdrp1 and Cdrp2 was done by PCR amplification. P. guajava methanolic extract was checked for the antifungal efficacy against the resistant strain of C. albicans. Further in-silico docking involves retrieval of ABC transporter protein and ligand optimization, molinspiration assessment on drug likeness, docking simulations and visualizations.
UNASSIGNED: 65% of the samples showed the presence of C.albicans and 2 strains were fluconazole resistant. Crude methanolic extract of P. guajava was found to be promising against the fluconazole resistant strains of C. albicans. In-silico docking analysis showed that Myricetin was a promising candidate with a high docking score and other drug ligand interaction scores.
UNASSIGNED: The current study emphasizes that bioactive compounds from Psidium guajava to be a promising candidate for treating candidiasis in fluconazole resistant strains of C. albicans However, further in-vivo studies have to be implemented for the experimental validation of the same in improving the oral health and hygiene.

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent.
OBJECTIVE: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC).
METHODS: We used Wood\'s light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method.
RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood\'s light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L.
CONCLUSIONS: Use of Wood\'s light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.

Fluconazole (2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol), which was patented in 1981 and introduced for commercial use in 1988, is a widely utilized antifungal drug whose mechanism of action involves inhibition of the activity of 14-α lanosterol demethylase. Its safety and effectiveness have established it as one of the most frequently employed antifungal agents. Resistance to azole antifungal drugs is becoming more common. It may be related to a mutation of the gene encoding the enzyme. To address this issue, molecules with modifications in three main regions of fluconazole, namely the hydroxyl group, the aromatic ring, and the 1,2,4-triazole rings, have been synthesized in an attempt to create more potent antifungal drugs. These modifications aim at enhancing the effectiveness against microorganisms and improving pharmacokinetic parameters and safety profiles of the synthesized compounds. The present review explores the synthesis of fluconazole derivatives, accompanied by insights into the results of biological studies evaluating the therapeutic effects of these compounds.

Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole\'s biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.

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Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six N-substituted phthalimides against three Candida species. Of the derivatives, N-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains.

The opportunistic fungal pathogen Candida parapsilosis is a major causative agent of candidiasis leading to death in immunocompromised individuals. Azoles are the first line of defense in treatment by inhibiting ERG11, involved in the synthesis of ergosterol, the main sterol fungal sterol. Resistance to azoles is on the increase worldwide including in Lebanon. The purpose of this study is to characterize nine hospital isolates labeled as C. parapsilosis: four resistant and five sensitive to fluconazole. Phenotypic characterization was achieved through a battery of tests that target pathogenicity attributes such as virulence, biofilm formation, stress resistance, and ergosterol content. Genotypic analysis was done through whole genome sequencing to mutations in key virulence and resistance genes. Phylogenetic comparison was performed to determine strain relatedness and clonality. Genomic data and phylogenetic analysis revealed that three of the nine C. parapsilosis isolates were misidentified; two as C. orthopsilosis and C. metapsilosis belonging to the C. parapsilosis complex, while the third was C. albicans. Moreover, several known and novel mutations in key drug resistance and virulence genes were identified such as ERG11, ERG3, ERG6, CDR1, and FAS2. Phylogenetic analysis revealed a high degree of relatedness and clonality within our C. parapsilosis isolates. Our results showed that resistant isolates had no increased ergosterol content, no statistically significant difference in virulence, but exhibited an increase in biofilm content compared to the sensitive isolates. In conclusion, our study, the first of its kind in Lebanon, suggests several mechanisms of antifungal drug resistance in C. parapsilosis hospital isolates.

BACKGROUND: Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women\'s quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care.
OBJECTIVE: To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS.
METHODS: A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication.
RESULTS: An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio.
CONCLUSIONS: This analysis highlights fluconazole\'s cost-effectiveness in current UK guidelines and favourability.

OBJECTIVE: To evaluate temporal changes in serum C-reactive protein (CRP) and haptoglobin (Hp) concentrations in dogs with pulmonary coccidioidomycosis and assess their utility to detect remission.
METHODS: 31 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021 were included in a retrospective cohort study that utilized archived serum. Serum was originally obtained at diagnosis and once every 3 months after antifungal administration until either remission or 12 months. Time points were designated as baseline (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). Serum CRP and Hp were measured at a reference laboratory with ELISA assays.
RESULTS: Median serum CRP and Hp concentrations decreased from T0 (CRP, 56 mg/L; Hp, 716.1 mg/dL) to T1 (CRP, 3.3 mg/L; Hp, 240.5 mg/dL); subsequent decreases were not significant. Eighteen (60%) and 16 (53%) of 30 dogs had normal serum CRP and Hp concentrations at T1, respectively. Absolute serum CRP (AUC, 0.58; 95% CI, 0.45 to 0.72) and Hp (AUC, 0.65; 95% CI, 0.52 to 0.78) were poor detectors of remission. However, the percentage change in Hp from T0 to T1 (AUC, 0.90; 95% CI, 0.74 to 1.0) was an excellent predictor of remission within 12 months.
CONCLUSIONS: Serum CRP and Hp concentrations decrease in the first 3 months of antifungal treatment in dogs with pulmonary coccidioidomycosis, and the percentage change of Hp may help predict dogs that will achieve remission within 12 months of treatment.
CONCLUSIONS: Serum CRP and Hp may be useful adjunctive biomarkers to monitor treatment response in dogs with pulmonary coccidioidomycosis.