Search Results (324)

Invasive infections with rare yeasts are increasing worldwide and are associated with higher mortality rates due to their resistance to antifungal drugs. Accurate antifungal susceptibility testing (AFST) is crucial for proper management of rare yeast infections. We performed AFST of 74 Candida kefyr isolates by Etest, EUCAST-based MICRONAUT-AM assay (MCN-AM) and reference Clinical and Laboratory Standards Institute broth microdilution method (CLSI). Essential agreement (EA, ±1 two-fold dilution), categorical agreement (CA), major errors (MEs) and very-major errors (VmEs) were determined using epidemiological cut-off values of ≤1.0 µg/mL, ≤0.03 µg/mL, ≤0.5 µg/mL and ≤1 µg/mL, defining wild-type isolates for fluconazole, voriconazole, micafungin and amphotericin B (AMB), respectively. Results for AMB susceptibility were correlated with ERG2/ERG3 mutations and total-cell sterols. CA of ≥97% was recorded between any two methods while EA varied between 72 and 82%, 87 and 92%, and 49 and 76% for fluconazole, voriconazole and micafungin, respectively. For AMB, CAs between CLSI and Etest; CLSI and MCN-AM; MCN-AM and Etest were 95% (4 ME, 0 VmE), 96% (3 ME, 0 VmE) and 99%, respectively, while EA varied from 32% to 69%. Non-synonymous ERG2/ERG3 mutations and no ergosterol were found in seven of eight isolates of non-wild types for AMB by Etest. Our data show that Etest, CLSI and MCN-AM methods are suitable for AFST of C. kefyr for fluconazole, voriconazole and micafungin. Excellent CAs for AMB between Etest and MCN-AM with concordant sterol profiles but not with CLSI suggest that Etest is also an excellent alternative for the detection of C. kefyr isolates with reduced susceptibility to AMB. Full article

Beach Sand Mycobiome is currently among the most important health challenges for viticulture in the world. Remarkably, the study of fungal communities in coastal beach sand and recreational waters remains underexplored despite their potential implications for human health. This research aimed to assess the prevalence of fungal species and the antifungal susceptibility profiles of fungi recovered from the beaches of the Persian Gulf and the Sea of Oman. Sand and seawater samples from 39 stations distributed within 13 beaches along the coastline were collected between May and July 2023. The grown isolates were identified at the species level based on morphological characteristics and DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical Laboratory Standards Institute guidelines. Of 222 recovered isolates, 206 (92.8%) filamentous fungi and 16 (7.2%) yeast strains were identified. Sand-recovered fungi comprised 82.9%, while water-originated fungi accounted for 17.1%. The DNA sequencing technique categorized 191 isolates into 13 genera and 26 species. The most recovered genus was Aspergillus (68.9%), and Aspergillus terreus sensu stricto was the commonly identified species (26.14%). Voriconazole was the most effective antifungal drug against Aspergillus species. Research on fungal contamination levels at these locations could provide a foundation for establishing regulatory frameworks to diminish fungal risks, thereby enhancing public health protection. The ecological significance of fungal communities in sandy beaches to human infections remains to be explored, and earlier reports in the literature may motivate researchers to focus on detecting this mycobiome in natural environments where further investigation is warranted. Ultimately, our discovery serves as a reminder that much remains to be learned about pathogenic fungi and underscores the need for vigilance in areas where emerging pathogens have not yet been identified. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea in the inpatient and community setting. Real-world data outside the strict environment of randomized controlled trials (RCTs) are needed to improve the quality of evidence. The aim of this study was to compare different clinical outcomes of CDI patients treated with fidaxomicin with those treated with vancomycin using a representative patient population in the United States of America (USA). Methods: Comprehensive real-world data were analyzed for this retrospective observational study, provided by the TriNetX database, an international research network with electronic health records from multiple USA healthcare providers. This includes in- and outpatients treated with fidaxomicin (FDX) or vancomycin (VAN) for CDI between 01/2013 and 12/2023. The following cohorts were compared: (i) patients treated with fidaxomicin within 10 days following CDI diagnosis (FDX group) vs. (ii) patients treated with vancomycin within 10 days following CDI diagnosis (VAN group). Outcomes analysis between the two cohorts was performed after propensity score matching and included event risk and Kaplan–Meier survival analyses for the following concomitant diseases/events occurring during an observational period of 12 months following CDI diagnosis: death, sepsis, candidiasis, infections caused by vancomycin-resistant enterococci, inflammatory bowel disease, cardiovascular disease, psychological disease, central line-associated blood stream infection, surgical site infection, and ventilator-associated pneumonia. Results: Following propensity score matching, 2170 patients were included in the FDX group and VAN groups, respectively. The event risk analysis demonstrated improved outcomes of patients treated with FDX compared to VAN in 6 out of the 10 events that were analyzed. The highest risk ratio (RR) and odds ratio (OR) were found for sepsis (RR: 3.409; OR: 3.635), candidiasis (RR: 2.347; OR: 2.431), and death (RR: 1.710; OR: 1.811). The Kaplan–Meier survival analysis showed an overall survival rate until the end of the 12-month observational period of 87.06% in the FDX group and 78.49% in the VAN group (log-rank p < 0.001). Conclusions: Our comparative event risk analysis demonstrated improved outcomes for patients treated with FDX compared to VAN in most of the observed events and underlines the results of previously conducted RCTs, highlighting the beneficial role of FDX compared to VAN. Further big data analyses from other industrialized countries are needed for comparison with our observations. Full article

Canine otitis externa is a prevalent condition, and inadequate treatment may favor the emergence of multidrug-resistant microorganisms. Drug repurposing provides an alternative approach for the management of this disease. Thus, this study aimed at assessing the antimicrobial and antibiofilm properties of levamisole against bacterial strains recovered from dogs with otitis externa as well as its influence on biofilm growth dynamics during 120 h. A total of 50 clinical bacterial isolates were subjected to analysis. Planktonic bacterial susceptibility to levamisole was assessed by broth microdilution to determine the minimum inhibitory concentration (MIC), the lowest concentration that completely inhibits bacterial growth. The activity against mature biofilms was assessed by determining the minimum biofilm eradication concentration (MBEC). The effect of levamisole on biofilm formation was evaluated at the MIC and at two subinhibitory concentrations, with daily readings recorded at 48, 72, 96, and 120 h. MICs of levamisole ranged from 0.58 to 2.34 mg/mL. Levamisole reduced the biomass of mature biofilms (p < 0.05), with MBEC values ranging from 1.17 to 18.75 mg/mL, and biofilm formation was significantly reduced at the MIC concentration (1.17 mg/mL) for all isolates for 120 h (p < 0.05). Levamisole demonstrated potential as a preventive approach against biofilm-associated bacterial otitis. Full article

Background: Trichophyton indotineae, a new emerging pathogen according to the WHO, is known to cause severe forms of tinea. Given that traditional identification methods rely on morphological characteristics, and the morphological distinctions among T. indotineae, T. mentagrophytes, and T. interdigitale are minimal, the adoption of alternative diagnostic techniques, such as RT-PCR or gene sequencing, has become critically important to prevent misidentification. The purpose of this study was firstly to analyze the local epidemiology of dermatophytes isolated and secondly to investigate the presence of T. indotineae among the isolated strains. Methods: Between January 2021 and June 2024, 1096 samples of skin adnexa were analysed. The isolated strains belonging to the genus Trichophyton were submitted to molecular identification by ITS sequencing, and T. indotineae strains were subjected to squalene epoxidase (SQLE) sequencing analysis. Results: Trichophyton rubrum and Trichophyton interdigitale appear to be the most prevalent pathogenic species. Molecular identification reveals four T. indotineae strains (4/87; 4.61%) from Asian patients, which were also characterized by gene mutations associated with terbinafine resistance. Conclusions: This study has made it clear that there is a need to implement basic mycological diagnostics with molecular methods to avoid misidentifications, ensure the correct identification, and evaluate the presence of mutations associated with antifungal drug resistance. Full article

Malaria remains a health problem, with Plasmodium falciparum accounting for 96% of cases in Africa and 15% in Brazil. The growing threat of drug resistance to artemisinin-based combination therapies (ACTs) jeopardizes progress toward elimination. This study examined P. falciparum samples collected from 141 patients in Brazil (2013–2023) by PCR and DNA sequencing to identify single-nucleotide polymorphisms in the pfcrt, pfmdr1, and pfk13 genes. Half of the samples carried the SVMNTMCGI haplotype in pfcrt, and none of the samples showed C350R mutations. In pfmdr1, the NYCDY haplotype was dominant (70%), with low occurrences of N86Y (4%) and no Y184F polymorphisms. No mutations linked to artemisinin partial resistance were detected in pfk13. Only one Amazonas sample exhibited wild-type haplotypes across all genes. Genetic diversity was more pronounced in pfcrt than pfmdr1, reflecting selective drug pressure. Significant linkage disequilibrium (LD) was observed within pfcrt (C72S and K76T) and pfmdr1 (S1034C and N1042D), but not between the two genes. The absence of pfk13-resistant mutations and the low prevalence of key pfmdr1 markers support the efficacy of ACTs. The persistence of diverse haplotypes and intragenic LD reflects ongoing drug pressure, underscoring the need for continuous genetic surveillance to anticipate emerging resistance. Full article

Background: Diet is known to influence the composition of the gut microbiome. For patients who require enteral feeding, there has been a growing popularity of using blenderized tube feeds (BTFs) as an alternative to standard enteral formula (SEF). There is limited literature exploring the impact of BTFs on the gut microbiome. Methods: Twenty-eight patients 1 to 22 years of age who received their nutrition via gastrostomy tube for over 4 weeks were included and participants were divided into BTF and SEF groups. Demographics and clinical information were collected from the medical records, and all legal guardians completed a semi-structured interview using a questionnaire. 16SrRNA sequencing was used for bacteriome analysis. Results: Eleven patients in the BTF group and seventeen in the SEF group were included. No significant differences in the demographics were noted. Patients on BTFs had no emesis compared to seven (41%) in the SEF group, p = 0.02. There were no significant differences in other clinical characteristics and comorbidities. No significant differences in the gut microbiome between the groups were noted for alpha and beta diversities, richness, and evenness (at both genus and species levels). Differential abundance analysis showed only a few significant differences between the groups at all reported taxonomic levels. Conclusions: Patients on BTFs had a significantly decreased prevalence of emesis compared to the SEF group. No significant differences in the microbiome between the groups were noted for alpha and beta diversities, richness, and evenness. Prospective studies are recommended to verify our preliminary data and further evaluate the implications of our study results. Full article

The global burden of fungal infections is rising at an alarming rate, with superficial, cutaneous, and mucosal mycoses among the most prevalent. Conventional treatments rely on oral and topical antifungal agents; however, these therapies are often limited by adverse effects, toxicity, frequent recurrence, and poor patient adherence due to prolonged treatment regimens. Moreover, the emergence of antifungal resistance and multidrug-resistant species such as Candidozyma auris and Trichophyton indotineae highlights the urgent need for alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). aPDT is based on photophysical and photochemical processes involving a photosensitizer (PS), a light source, and molecular oxygen. When combined, these elements generate reactive oxygen species that selectively destroy microbial cells. In this review, we explore various PSs and their effectiveness in aPDT against infections caused by dermatophytes, Candida spp., and other pathogenic fungi. Promisingly, aPDT has demonstrated antifungal activity against both susceptible and resistant strains. In addition, aPDT has been successfully used in cases of mycoses unresponsive to conventional therapies, showing favorable clinical outcomes and overall safety. Current evidence supports aPDT as a valuable strategy for the management of cutaneous, mucosal, and superficial fungal infections and as a potential strategy to combat antifungal resistance. Full article

Dermatophytosis is a fungal infection that affects the skin, hair, and nails, impacting approximately 25% of the global population. Nannizzia gypsea is a geophilic fungus that can cause infections in humans and animals. Several studies have been conducted regarding its virulence, or ability to cause disease. This species may produce keratinolytic enzymes and form biofilms, which can increase resistance to treatment. Thus, this study focuses on investigating the biofilm formation of N. gypsea isolated from canine dermatophytosis using an ex vivo hair model, its biofilm extracellular matrix macromolecular contents, and the expression of genes involved in the colonization of keratinized surfaces. The biofilm was analyzed for metabolic activity using the XTT reduction assay, crystal violet staining to measure biofilm biomass, scanning electron microscopy (SEM), and the presence of polysaccharides, proteins, and extracellular DNA in the biofilm extracellular matrix. The virulence genes subtilisin 7, fungalysin (extracellular metalloproteinase), and efflux pump (Multidrug and Toxin Extrusion Protein 2) were evaluated by qPCR, comparing the planktonic and biofilm phenotypes. N. gypsea formed a robust biofilm, which matured after 5 days. Scanning electron microscopy (SEM) revealed the presence of an extensive extracellular matrix. In the hair model, the characteristic ectothrix parasitism of the species is observable. The gene expression analysis revealed a higher expression of all evaluated genes in the biofilm form compared to the planktonic form. Thus, N. gypsea exhibits a biofilm characterized by a robust extracellular matrix and high gene expression of factors related to pathogenesis and resistance. Full article

Yeast bloodstream infections lead to high mortality and morbidity and are mostly observed in immunocompromised patients. In Africa, only a few studies have characterized clinical yeasts. To increase insight into yeast resistance and transmission in Africa, we identified various yeasts from Alexandria, Egypt and performed antifungal susceptibility testing (AFST) and genotyping. A total of 1307 single isolates from unique patients, recovered from different anatomical sites including the bloodstream, retrieved from a reference laboratory in Alexandria, Egypt were studied. All isolates were identified with MALDI-TOF MS, while some were initially identified with a Vitek 2 Compact system. Short tandem repeat (STR) genotyping was performed for the most common species, and AFST was performed with microbroth dilution. Among bloodstream isolates (n = 71), C. albicans was the most common etiological agent, followed by C. tropicalis and C. parapsilosis. Comparison of yeast identification methods demonstrated that 22% of isolates were incorrectly identified with the Vitek 2 Compact system compared to MALDI-TOF MS. Multiple rare yeasts showed reduced antifungal susceptibility. STR genotyping demonstrated potential events of nosocomial transmission with N. glabratus and C. parapsilosis. Moreover, an azole-resistant C. tropicalis clade identified earlier in Alexandria was still present. To conclude, clinical yeasts in Alexandria, Egypt, are overall susceptible common species. Full article

Background: Trichophyton indotineae terbinafine-resistant infections are emerging in healthy individuals. Luliconazole, an imidazole antifungal that is effective against skin infections, faces challenges due to low water solubility and poor skin penetration. This study aimed to formulate a luliconazole-loaded nanostructured lipid-carrier (NLC) gel in a Carbopol-based system to enhance drug absorption and efficacy in a guinea pig model of dermatophytosis. Methods: Luliconazole-loaded nanostructured lipid carriers (NLCs) were prepared using a solvent evaporation method and gel formulation. Skin absorption and retention were assessed via Franz diffusion cells. The antifungal efficacy was tested against T. indotineae in thirty guinea pigs with induced tinea corporis, divided into five treatment groups. Mycological, clinical, and histopathological evaluations were conducted, along with skin irritation studies for safety. Results: LCZ-NLC demonstrated significantly better skin penetration than simple luliconazole gel, with cumulative drug penetration of 71.8 ± 3.7 μg/cm² versus 50.9 ± 4.2 μg/cm² after 24 h. Both formulations achieved complete infection resolution after 21 and 28 days, with reduced inflammation and no local irritations. On day 21, the LCZ-NLC 1% gel significantly reduced lesion scores and mycological evidence of infection compared to the terbinafine-treated groups, untreated controls, and NLC-gel-treated group (p < 0.05). Histopathological analysis indicated a reduction in both epidermal thickening and fungal burden in the models that received treatment with the LCZ-NLC 1% gel. Conclusions: Luliconazole-loaded lipid carriers enhance drug absorption and efficacy, suggesting shorter treatment durations and improved patient outcomes for resistant fungal infections. However, further studies are warranted to correlate these findings with clinical outcomes. Full article

Background/Objectives: Small Intestinal Bacterial Overgrowth (SIBO) and Small Intestinal Fungal Overgrowth (SIFO) are distinct yet often overlapping conditions characterized by an abnormal increase in microbial populations within the small intestine. SIBO results from an overgrowth of colonic bacteria, while SIFO is driven by fungal overgrowth, primarily involving Candida species. Both conditions present with nonspecific gastrointestinal (GI) symptoms such as bloating, abdominal pain, diarrhea, and malabsorption, making differentiation between SIBO and SIFO challenging. This review aims to elucidate the underlying mechanisms, risk factors, diagnostic challenges, and management strategies associated with SIBO and SIFO. Methods: A comprehensive review of current literature was conducted, focusing on the pathophysiology, diagnostic modalities, and therapeutic approaches for SIBO and SIFO. Results: SIBO is commonly associated with factors such as reduced gastric acid secretion, impaired gut motility, and structural abnormalities like bowel obstruction and diverticula. It is frequently diagnosed using jejunal aspirates (≥10⁵ colony forming units (CFUs)/mL) or breath tests. In contrast, SIFO is linked to prolonged antibiotic use, immunosuppression, and gut microbiome dysbiosis, with diagnosis relying on fungal cultures from small intestinal aspirates due to the absence of standardized protocols. Conclusion: The clinical overlap and frequent misdiagnosis of SIBO and SIFO highlight the need for improved diagnostic tools and a multidisciplinary approach to management. This review emphasizes the importance of understanding the mechanisms behind SIBO and SIFO, how they relate to other health outcomes, and potential management strategies to optimize patient care and therapeutic outcomes. Full article

Chronic fungal sinusitis (FS) can cause bone erosion and extend to the sellar region, often misdiagnosed as pituitary tumors or malignancies. We report a 56-year-old immunocompetent female with sphenoid FS presenting as a giant sellar mass compressing the optic chiasm, with normal pituitary function. The surgery successfully resolved her symptoms, and a histological examination confirmed the presence of a fungal hyphal mass. We conducted a literature review of 52 publications on FS cases with bone erosion and inflammatory extension to the sellar region, which included analyses of 67 patients (35 females, mean age 49.6 years, half immunocompetent). The most common symptom was headache (73.1%), followed by visual complaints (71.7%), visual deterioration (40.3%), ophthalmoplegia (38.8%), and visual field defects (13.4%). Symptom duration averaged 4.5 months in 65.7% of cases. Aspergillus was the most frequent (71.6%). Hormonal abnormalities included hypopituitarism (25.4%) and hyperprolactinemia (13.4%). Surgery was performed in 92.5% of patients. Common diagnoses included pituitary abscess (41.8%), fungal granuloma (16.4%), aspergillosis (16.4%) and allergic FS (14.9%). Antifungal therapy was administered in 53.7% of cases. Cure was achieved in 67.2%, while the mortality rate was 10.4%. Early recognition of fungal involvement, supported by a multidisciplinary approach, is essential for the accurate diagnosis and effective treatment. This highlights the need for vigilance to improve the outcomes in similar cases. Full article

Cystic fibrosis is a severe, inherited, life-limiting disorder, and over half of those living with CF are children. Persistent airway infection and inflammation, resulting in progressive lung function decline, is the hallmark of this disorder. Aspergillus colonization and infection is a well-known complication in people with CF and can evolve in a range of Aspergillus disease phenotypes, including Aspergillus bronchitis, fungal sensitization, and allergic bronchopulmonary aspergillosis (ABPA). Management strategies for children with CF are primarily aimed at preventing lung damage and lung function decline caused by bacterial infections. The role of Aspergillus infections is less understood, especially during childhood, and therefore evidence-based diagnostic and treatment guidelines are lacking. This narrative review summarizes our current understanding of the impact of Aspergillus on the airways of children and young people with CF. Full article

Background: Systemic therapy is frequently utilized because of its easy accessibility, low cost, and high efficacy. However, it can be linked with systemic adverse effects and drug–drug interactions, especially in immunocompromised and poly-medicated patients. Topical antifungals, associated with a low risk of systemic adverse effects and drug–drug interactions, have emerged as the most suitable treatment option for patients with diabetic foot disease. However, the duration of topical treatment can extend up to 12 months. Consequently, there is a need to bolster these topical treatments with complementary therapies. Methods: The current study acquired approval from an ethics committee (code 24/241-E) and Clinical Trials (code NCT06485050). No patients were excluded, irrespective of comorbidities or the severity of onychomycosis. Patients included in the study were administered Ciclopirox 8% (consisting of ethyl acetate, 96% ethanol, ketostearyl alcohol, hydroxypropyl chitosan, and purified water) once daily for 6 months. This was supplemented with photodynamic therapy (three sessions in the first 2 months) using toluidine blue gel and a 635 nm diode laser lasting 10 min, as well as monthly debridement of the nail plate. Results: All patients (10/10) included in the study exhibited negative microbiological culture results 6 months after the study began. Of these, 90% (9/10) were clinically cured, and thus, fully cured. No adverse effects or complications secondary to the treatments were observed in any of the cases. The average Onychomycosis Severity Index (OSI) value was initially 18.50 ± 8.947, reduced to 10.30 ± 6.129 at 3 months, and finally fell to 4.10 ± 4.08 at the end of the treatment. Conclusions: The current study demonstrated the clinical improvement, mycological cure, effectiveness, and safety of combination therapy of ciclopirox 8% and photodynamic therapy over 6 months. Full article