Current Medical Mycology最新文献

Background and purpose: In the context of HIV/AIDS, cryptococcosis emerges as one of the most common opportunistic infections, with a predilection for affecting individuals with compromised immune function.

Case report: This study aimed to present a compelling case of disseminated cryptococcosis in a 29-year-old male with a complex medical history, marked by HIV infection, hepatitis C, and a longstanding history of intravenous drug abuse. Blood sample of the patient as well as the cerebrospinal fluid sample grew Cryptococcus neoformans. Immunochromatographic test performed on CSF and serum sample was also positive.

Conclusion: Chronic Hepatitis C Virus can disrupt the blood-brain barrier and cause neuroinflammation predisposing the central nervous system to hematogenous seeding during fungemia. Multifaceted medical background of the patient underscored the challenges in the management of comorbidities.

Background and purpose: Fluconazole is one of the primary antifungal agents in the treatment of candidiasis. However, long-term treatment and indiscriminate use of drugs from the azole family have created resistant isolates. Candida albicans cells can develop resistance to fluconazole through various mechanisms. The present study aimed to investigate the expression of genes involved in fluconazole resistance in C. albicans in people with different underlying diseases.

Materials and methods: Databases, such as PubMed, Scopus, and Web of Science were used to collect studies evaluating the expression levels of key C. albicans genes associated with fluconazole resistance from 1997 to 2024. Finally, 25 out of the 1,096 extracted studies were selected based on the inclusion and exclusion criteria.

Results:  This systematic review identified the genes encoding the ATP-binding cassette membrane pump (CDR1, CDR2) and the genes encoding the major facilitator superfamily pumps (MDR1), as well as the ERG11 gene, are the most important effective genes in creating resistance of C. albicans to fluconazole. Based on the studies conducted since 1995, the CDR1 gene has the highest gene expression among the genes involved in resistance, followed by ERG11, MDR1, and CDR2, respectively.

Conclusion: Comprehensive information about the activity of the genes and more studies on the genes involved in resistance, could provide valuable insights for further studies, prevent the occurrence of resistance to fluconazole and other azoles, and provide suitable treatments. The disease, as well as the dosage and duration of the antifungal therapy, may play an important role in determining the type of resistance mechanism of C. albicans. Therefore, further evaluation of the role of these genes in fluconazole-resistant species, along with their related gene products, is necessary.

Background and purpose: Onychomycosis, a prevalent fungal infection affecting the nails, presents considerable difficulties in clinical treatment. Zataria multiflora (Zat), with its known antifungal properties, presents a promising approach for treatment. The present study focused on the evaluation of the effectiveness of Zat-NLC 1% gel against mold-associated onychomycosis, compared to a placebo.

Materials and methods: The Zat-loaded nanostructured lipid carriers (Zat-NLCs) were prepared and optimized by utilizing an ultrasonic probe approach. Antifungal susceptibility testing followed Clinical and Laboratory Standards Institute M38-A3 guidelines on the most common dermatophytes and non-dermatophytes fungal species. A double-blind trial with 40 participants (20 volunteers from each gender, equally divided into two groups, namely Zat-NLCs 1% gel and placebo receivers) evaluated Zat-NLC 1% gel efficacy. Causative agents were identified at the species level using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: A mono-dispersed suspension of spherical nanoparticles with zeta potential, Z-average, and polydispersity index of -26.6±7.7 mV, 273.9±3 nm, and 0.369±0.03, respectively, was achieved with no cytotoxicity. The Zat-NLCs demonstrated a significant inhibitory effect on both dermatophytes and non-dermatophyte fungal growth, in vitro. Effective improvement was observed in mycological criteria, compared to the placebo group (P<0.005) after 2 weeks of treatment. The mycological cure rate was 70% for Zat-NLCs gel after only 2 weeks. The results were notably different from those observed in the placebo group following the same duration of application (70% vs. 55%). However, the difference was insignificant in the mentioned groups after 4 weeks of application due to the prescription of routine antifungals for onychomycosis. The PCR-RFLP outputs revealed T. mentagrophytes/interdigitale complex and A. section Flavi as the predominant isolated species of dermatophytes and non-dermatophytes, respectively.

Conclusion: Nanoscale colloidal systems loading with antifungals might be strongly considered a better and more efficient cure for mold-related dermatophytosis.

Background and purpose: Fungal infections necessitate advanced delivery systems to improve antifungal therapy. Terbinafine, a potent allylamine antifungal, faces clinical limitations due to poor solubility, low bioavailability, and toxicity. Liposomal encapsulation addresses these challenges by enhancing solubility, enabling controlled release, and reducing toxicity. In this study, a scalable ethanol injection method was used to develop terbinafine-loaded liposomes with optimized physicochemical properties. This study aimed to focus on central nervous system-targeted delivery to combat resistant fungal infections while minimizing systemic toxicity.

Materials and methods: Twenty liposomal formulations were prepared using phospholipids (e.g., dipalmitoylphosphatidylcholine [DPPC], hydrogenated soybean phosphatidylcholine) and characterized for size, zeta potential, polydispersity index, and morphology via dynamic light scattering and transmission electron microscopy. Encapsulation efficiency, drug release kinetics, colloidal stability (3 months), and cytotoxicity (human foreskin fibroblast 2 cells, 48-hour exposure) were evaluated. The M38-A2 method of the Clinical and Laboratory Standards Institute was used to calculate minimum inhibitory concentrations (MICs) of 16 azole-susceptible and -resistant Aspergillus fumigatus and Aspergillus flavus.

Results: Liposomes exhibited sizes of 72-174 nm, zeta potentials between +2 and -15 mV, and a low polydispersity index (<0.3). Moreover, F12 (DPPC-based) demonstrated superior cumulative release, compared to F20, and attributed to the fluid bilayer of DPPC. Both formulations retained stability during storage. Cytotoxicity assays revealed minimal toxicity for free terbinafine (14.73% at 25 mg/mL) and significantly reduced toxicity for liposomal forms (6.77% for F12, p<0.05). The DPPC-based formulation achieved an encapsulation efficiency of 73.48%, ensuring a high drug payload and biocompatibility. The DPPC-based formulation achieved an encapsulation efficiency of 73.48%, ensuring a high drug payload and biocompatibility. Liposomal terbinafine and voriconazole exhibited good in vitro activity against both triazole-susceptible and -resistant Aspergillus isolates (MIC₅₀=0.5 µg/mL).

Conclusion: Based on the results, F12, with its sub-100 nm size, sustained release, and reduced cytotoxicity, emerged as a promising candidate for brain-targeted antifungal therapy. Its stability and high encapsulation efficiency support further evaluation in fungal isolates and in vivo models to optimize central nervous system biodistribution and therapeutic efficacy. In addition, this study underscored the promising in vitro activities of terbinafine and liposomal terbinafine against both triazole-resistant/susceptible A. fumigatus and A. flavus.

Background and purpose: Dermatophytosis, or ringworm, is a highly contagious fungal infection caused by dermatophytes, like Microsporum canis, which primarily affects cats and dogs and poses a significant zoonotic threat. Increasing prevalence of drug-resistant strains complicates the treatment of M. canis infections, necessitating the exploration of new therapeutic approaches. Nanotechnology, particularly copper oxide nanoparticles (CuO NPs), has emerged as a promising solution due to its potent antimicrobial properties and potential to overcome resistance. This study aimed to evaluate the antifungal efficacy of CuO NPs against M. canis isolates collected from companion animals. The goal was to develop more effective treatment options for dermatophytosis, addressing the need for alternative therapies and the challenge of antifungal resistance.

Materials and methods: CuO NPs were synthesized using a green chemistry approach, employing Eichhornia crassipes leaf extract. Concurrently, M. canis isolates were obtained from infected animals and cultured for purity. Antifungal activity of the CuO NPs against the isolates was assessed through disk diffusion and microdilution tests, and the results were statistically analyzed to confirm their significance. Cell dens (10 ⁵ .

Results:  The synthesized CuO NPs exhibited high purity, small size, and cubic morphology. Statistical analysis of the disk diffusion and microdilution tests confirmed the significant antifungal efficacy of CuO NPs against M. canis isolates (ANOVA, p<0.05). Minimum inhibitory concentration (MIC) values ranged from 500 to 1,000 ppm, while minimum fungicidal concentration (MFC) values were between 1,000 and 2,000 ppm. Average MFC/MIC ratio of 2.6, confirmed through paired t-test (p=0.003), demonstrated the fungicidal properties of the CuO NPs.

Conclusion: This study highlighted the potent antifungal capabilities of CuO NPs against M. canis, marking them as a promising alternative to conventional treatments. With further optimization and research, CuO NPs could revolutionize the management of dermatophytosis, offering a new frontier in combating drug-resistant fungal infections.

Background and purpose: Essential oils (EO) have gained significant attention due to their natural antimicrobial and antifungal properties. However, their application is often limited due to poor solubility, volatility, and stability. Nanoemulsions, as advanced delivery systems, can overcome these limitations by enhancing the bioavailability and efficacy of EOs. Lemon EO, known for its broad-spectrum antimicrobial activity, is a promising candidate for nanoemulsion formulation. This study aimed to synthesize and characterize lemon EO nanoemulsions and evaluate their enhanced antimicrobial and antifungal potential, compared to crude oil.

Materials and methods: Lemon EO was first analyzed using gas chromatography-mass spectrometry (GC-MS) to identify its chemical composition. Lemon EO nanoemulsions were prepared using the spontaneous emulsification technique. The physicochemical properties, including particle size, polydispersity index (PDI), zeta potential, and stability, were characterized using dynamic light scattering. The antimicrobial and antifungal activities were assessed against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Candida albicans, and Aspergillus fumigatus through minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) assays.

Results: The GC-MS analysis revealed the major chemical components of lemon EO, including limonene, β-pinene, and γ-terpinene. The nanoemulsions exhibited a mean particle size of about 15 nm, a low PDI (< 0.3), and a negative zeta potential, indicating high stability and homogeneity. The antimicrobial and antifungal activities of the nanoemulsions were significantly enhanced compared to the crude lemon EO, as demonstrated by lower MIC and MFC values. The nanoemulsions also showed excellent stability under various storage conditions.

Conclusion: This study demonstrated that lemon EO nanoemulsions are a stable delivery system with superior antimicrobial and antifungal properties. The GC-MS analysis provided valuable insights into the chemical composition of the EO, further supporting its efficacy. These findings suggest the potential of lemon EO nanoemulsions as a natural alternative for applications in food preservation, pharmaceuticals, and cosmetics.

Background and purpose: Today, with the development of critical patient care and the increase in intravascular invasive methods, the survival rate of patients diagnosed with hematological and solid organ malignancies is increasing, and unfortunately, the incidence of Candida parapsilosis candidemia is also increasing due to multiple risk factors. In this study, we aimed to determine the clinical-demographic characteristics of C. parapsilosis candidemia and the antifungal susceptibility profile of C. parapsilosis in pediatric patients with hematological and solid organ malignancies.

Materials and methods: The present study included pediatric patients with hematologic and solid organ malignancies presenting with signs and symptoms consistent with candidemia, in whom C. parapsilosis was isolated from blood and catheter cultures between January 2010 and August 2023.

Results: Thirty (65.2%) of the patients had hematologic and 16 (34.8%) had solid organ malignancies. In all patients, 23 (50%) had non-catheter-related candidemia and 23 (50%) had catheter-related candidemia. At least one of the risk factors examined was detected in these patients. Catheter-related candidemia was found to be more common in patients diagnosed with hematologic malignancy. The difference was found to be statistically significant (p= 0.030). Drug resistance rates of C. parapsilosis were 6.5% for amphotericin B, 6.5% for fluconazole, 2.2% for voriconazole and 2.2% for micafungin. No patient with caspofungin resistance was detected. The mean treatment duration of the patients was 21 days (min 3-max 103) and it was observed that amphotericin B and caspofungin were used most frequently in the treatment regimen. The mortality rate of patients with candidemia was 6.5%.

Conclusion: Our study showed that patients with hematologic malignancies exhibited a higher susceptibility to catheter-related C. parapsilosis candidemia compared to patients with solid organ tumors. Caspofungin resistance was not detected in our study, and we believe that each center should know its own antifungal drug sensitivity, determine the treatment regimen accordingly, and that catheters should be removed rapidly in patients with catheter-related C. parapsilosis candidemia in malignant patients.

Background and purpose: Candida albicans is currently recognised as an opportunistic pathogen that can cause many invasive infections. Resistance mechanisms and fungal virulence factors play an important role in the effectiveness of treatment. The aim of this study was to investigate the relationship between fluconazole resistance, proteinase activity and ERG11 (sterol 14-demethylase)- SAP2 (secreted aspartic protease 2) gene expression levels in C.albicans strains.

Materials and methods: Candida albicans strains isolated from patient samples sent to Medical Microbiology laboratory of Düzce University from various clinics were included in the study. Fluconazole susceptibilities of the isolates were determined by broth microdilution method. The increase in fluconazole MIC values at 48 hours and proteinase activities of the isolates were analysed. ERG11 and SAP2 gene expression levels were measured by real time qPCR.

Results: Fluconazole resistance rate was found to be 3.14% in 127 C. albicans strains. A moderate positive correlation was found between ERG11 and SAP2 values (p=0.029, r:0.655, p<0.001). There was no correlation between SAP2/ERG11 expression levels and fluconazole resistance. Proteinase positivity was detected in 81.1%, of 127 strains and no statistically significant correlation was found between proteinase activities and SAP2/ERG11 expression levels. While there was a statistically significant relationship between ERG11 expression levels and 48th hour MIC elevation, there was no statistically significant relationship between SAP2 levels and 48th hour MIC elevation.

Conclusion: In addition to the moderate positive correlation between ERG11 and SAP2 values, a significant correlation was found between ERG11 expression and fluconazole tolerance.

Background and purpose: Candidiasis is a prevalent fungal infection caused by various species of Candida, especially, C. albicans. The emergence of resistance to azole medications, which are frequently prescribed for the treatment of Candida infections, presents a significant challenge in the management of these infections.

Materials and methods: The present mini-review summarizes findings from a comprehensive search of articles published between 1999 and 2024, retrieved from Scopus, PubMed, and Web of Science. Studies were selected using specific keywords based on relevance to UPC2 gene functions, azole resistance mechanisms, and C. albicans biology.

Results: The UPC2 gene has become crucial in regulating drug resistance in C. albicans. This gene encodes a zinc (II)-Cys (6) transcription factor involved in the biosynthesis of sterols and contributes to resistance against azole antifungal drugs. When exposed to azoles, UPC2 in C. albicans enhances the expression of ergosterol biosynthesis genes, such as ERG2 and ERG11. Increased expression of ERG11 leads to reduced susceptibility to azoles by boosting the production of 14α-lanosterol demethylase, the primary target of these antifungal agents. Furthermore, UPC2 regulates sterol uptake under anaerobic conditions and manages other adaptations to environmental changes, all of which contribute to azole resistance.

Conclusion: Gaining insight into how the UPC2 gene contributes to azole resistance is essential for the development of effective strategies in the antifungal drug development process.

Background and purpose: Oral candidiasis (OC) is a common condition in HIV-infected individuals. This study aimed to identify the prevalence, associated factors, and causative agents of OC among HIV-infected patients in a general hospital in Vietnam.

Materials and methods: The study involved 393 HIV-infected individuals treated at The Tropical Diseases Center, Nghe An General Friendship Hospital, Vinh, Nghe An, Vietnam from January 2022 to May 2024. The sample collected from the buccal mucosa was seeded onto CHROMagar^TM Candida to isolate and identify the causative yeasts. Molecular identification was performed with restriction fragment length polymorphism assay using MspI restriction enzyme and sequencing of the internal transcribed spacer (ITS) region.

Results: The prevalence of OC was 10.7% (95% confidence interval 7.6 - 13.8). Patients with late WHO HIV clinical stage, poorer hygienic condition, or use of prosthetic were at a higher risk of OC. Ten yeast species were isolated, and 10 (23.8%) patients carried more than one type of yeast species. Out of 54 obtained isolates, Candida albicans comprised the most (62.9% isolates and 80.9% patients), followed by C. tropicalis (16.4% and 21.4% respectively). Overall, 27 patients (64.3%) were infected with C. albicans, and 15 patients (35.7%) were infected with non- albicans Candida, alone or in combination with C. albicans.

Conclusion: The prevalence of OC in HIV-infected patients was low and associated with both systemic and local factors. C. albicans was still the most common species but non- albicans Candida or coexistence of Candida species is frequent.