Search Results (189)

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Candida albicans is a clinically important fungal pathogen capable of causing both superficial and systemic infections, particularly in immunocompromised individuals. A key factor contributing to its pathogenicity is its ability to form biofilms, structured microbial communities that confer significant resistance to conventional antifungal therapies. Addressing this challenge, we explored the antivirulence potential of acridine derivatives, a class of heterocyclic aromatic compounds known for their diverse biological activities, including antimicrobial, antitumor, and antiparasitic properties. In this study, a series of acridine derivatives was screened against C. albicans biofilms, revealing notable inhibitory activity and highlighting their potential as scaffolds for the development of novel antifungal agents. Among the tested compounds, acridine-4-carboxylic acid demonstrated the most promising activity, significantly inhibiting the biofilm formation at 10 µg/mL without affecting planktonic cell growth, and with a minimum inhibitory concentration (MIC) of 60 µg/mL. Furthermore, it attenuated filamentation and cell aggregation in a fluconazole-resistant C. albicans strain. Toxicity assessments using Caenorhabditis elegans and plant models supported its low-toxicity profile. These findings highlight the potential of acridine-based scaffolds, particularly acridine-4-carboxylic acid, as lead structures for the development of therapeutics targeting both fungal growth and biofilm formation in Candida albicans infections. Full article

Zeolites, microporous aluminosilicates with tuneable physicochemical properties, have garnered increasing attention in dermatology due to their antimicrobial, detoxifying, and drug delivery capabilities. This review evaluates the structural characteristics, therapeutic mechanisms, and clinical applications of zeolites—including clinoptilolite, ZSM-5, ZIF-8, and silver/zinc-functionalized forms—across skin infections, wound healing, acne management, and cosmetic dermatology. Zeolites demonstrated broad-spectrum antibacterial and antifungal efficacy, enhanced antioxidant activity, and biocompatible drug delivery in various dermatological models. Formulations such as silver–sulfadiazine–zeolite composites, Zn–clinoptilolite for acne, and zeolite-integrated microneedles offer innovative avenues for targeted therapy. Zeolite-based systems represent a promising shift toward multifunctional, localized dermatologic treatments. However, further research into long-term safety, formulation optimization, and clinical validation is essential to transition these materials into mainstream therapeutic use. Full article

Background: Exophiala dermatitidis is a dematiaceous, thermotolerant, yeast-like fungus increasingly recognized as an opportunistic pathogen in chronic airway diseases. While commonly associated with cystic fibrosis, its clinical significance in non-cystic fibrosis bronchiectasis (NCFB) remains unclear. Case Presentation: We report the case of a 66-year-old immunocompetent woman with a history of breast cancer in remission and NCFB, who presented with chronic cough and dyspnea. Chest CT revealed bilateral bronchiectasis with new pseudonodular opacities. Bronchoalveolar lavage cultures identified E. dermatitidis, along with Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. Given clinical stability and the absence of systemic signs, initial therapy included oral voriconazole, levofloxacin, doxycycline, and inhaled amikacin. Despite persistent fungal isolation on repeat bronchoscopy, the patient remained asymptomatic with stable radiologic and functional findings. Antifungal therapy was discontinued, and the patient continued under close monitoring. The patient exhibited clinical and radiological stability despite repeated fungal isolation, reinforcing the hypothesis of persistent colonization rather than active infection. Discussion: This case underscores the diagnostic challenges in distinguishing fungal colonization from true infection in structurally abnormal lungs. In NCFB, disrupted mucociliary clearance and microbial dysbiosis may facilitate fungal persistence, even in the absence of overt immunosuppression. The detection of E. dermatitidis should prompt a comprehensive evaluation, integrating clinical, radiologic, and microbiologic data to guide management. Voriconazole is currently the antifungal agent of choice, though therapeutic thresholds and duration remain undefined. Conclusions: This report highlights the potential role of E. dermatitidis as an under-recognized respiratory pathogen in NCFB and the importance of a multidisciplinary, individualized approach to diagnosis and treatment. This case underscores the need for further research on fungal colonization in NCFB and the development of evidence-based treatment guidelines. Further studies are needed to clarify the pathogenic significance, optimal management, and long-term outcomes of E. dermatitidis in non-CF chronic lung diseases. Full article

Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)–foam hybrid system, i.e., “nanoemulfoam” (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20/ethanol as the surfactant/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 ± 2.84 nm, ZP of −13.90 ± 0.99 mV, and DE% of 68.50 ± 1.78% (mean ± SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p < 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p < 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation. Full article

This study presents the development and comprehensive characterization of biopolymer-based nanofibrous composites composed of polyvinyl alcohol (PVA), chitosan (CS), boric acid (BA), and a natural antifungal agent natamycin (NAT), designed for therapeutic applications. A dual-layer 3D-fiber composite (PVA/CS/BA_PVA/NAT) was successfully fabricated using a layer-by-layer 3D bioprinting technique and electro-spinning, integrating BA into the core matrix and NAT into the outer layer. Mechanical tests revealed a significantly improved elastic modulus of 763.04 ± 14.54 MPa and the highest ultimate tensile stress (50.45 ± 2.58 MPa) among all samples. Despite a moderate strain at break (11.77 ± 0.49%), the composite preserved sufficient elasticity suitable for biological interfaces. Morphological assessment via SEM confirmed the successful deposition of continuous and bead-free nanofibers, with controlled fiber alignment and reduced average fiber diameters, especially in the BA-incorporated structure. The dual-layered system displayed enhanced uniformity and structural coherence. The drug release analysis demonstrated sustained NAT delivery over a 90 min period. Kinetic modeling showed a high correlation with the Korsmeyer–Peppas model (R² > 0.99), suggesting diffusion-controlled release, supported by the Korsmeyer–Peppas model’s Fickian diffusion exponent. In contrast, zero- and first-order models exhibited weaker fits, underscoring the relevance of a matrix-based release mechanism governed by the layered configuration. Crucially, antifungal assays against Candida albicans revealed substantial bioactivity. The PVA/CS/BA_PVA/NAT formulation achieved the largest inhibition zone (1.64 ± 0.13 cm), significantly outperforming single-layer controls such as PVA/CS/BA (1.25 ± 0.08 cm) and PVA/CS_PVA/NAT (1.43 ± 0.08 cm), while neat PVA exhibited no inhibition. These results confirm the synergistic antifungal efficacy of BA and NAT within the dual-layer structure. Together, these findings highlight the potential of the 3D-printed PVA/CS/BA_PVA/NAT composite as a mechanically robust, morphologically optimized, and bioactive platform for antifungal therapy and wound-healing applications. Full article

Previous studies have demonstrated that Candida spp. isolates exposed in vitro to the folic acid antagonist methotrexate may develop multidrug cross-resistance to azole antifungals. The aim of this study was to determine whether systemic therapy with antineoplastic antifolates—pemetrexed or methotrexate—constitutes a risk factor for colonization or infection with fluconazole-resistant yeasts. The study group comprised 44 cancer patients who received high-dose systemic antifolate therapy, while the control group consisted of 48 patients without prior exposure to either methotrexate or pemetrexed. Oral swabs and relevant clinical data were collected from all participants. In total, 109 fungal strains representing 13 species were isolated, identified, and subsequently tested for fluconazole susceptibility. Fluconazole-resistant isolates were identified in 4 out of 44 (9.1%) antifolate-treated patients and in 3 out of 48 (6.3%) control patients. Our findings suggest that, although this phenomenon occurs in vitro, systemic antineoplastic antifolate therapy does not induce azole resistance among endogenous yeast species in vivo. Full article

Background: Cryptococcus species constitute opportunistic fungi that seldom cause infections in individuals with competent immune systems. In the rare case of cryptococcal endocarditis, the fungus infiltrates the endocardium. This disease occurs almost exclusively in patients with active immunosuppression, implanted cardiac devices, or prosthetic valves. Objectives: This study aims to analyze all documented cases of Cryptococcus spp. endocarditis in humans, emphasizing the epidemiology, microbiology, clinical manifestations, therapeutic approaches, and infection outcomes. Methods: A comprehensive review was performed by searching the PubMed and Scopus databases. Results: A total of 16 studies reported data on 16 patients diagnosed with cryptococcal endocarditis. The mean patient age was 46.6 years, with males comprising 81.25% of cases. Immunosuppression was the most prevalent predisposing factor (31.25%), followed by a history of end-stage renal disease and prosthetic cardiac valves (25%). The most commonly affected intracardiac sites were the mitral (60%) and aortic valve (46.6%), while in 33.3% of cases, multiple-valve infection was observed. Cryptococcus neoformans was detected as the causative organism in the majority of cases (87.5%). The most frequently administered antifungal treatments included amphotericin B (87.5%) and fluconazole (43.75%), with combination therapy used in 62.5% of cases. Overall mortality was relatively high at 56.25%, with 50% of deaths directly attributed to the infection. Conclusions: Considering the ability of Cryptococcus spp. to induce severe systemic infections, healthcare providers should consider this pathogen in the differential diagnosis when yeast microorganisms are identified in microbiological samples. This is particularly crucial for patients with underlying comorbidities or immunodeficiency, as early recognition is crucial to ensure precise diagnosis and treatment. Full article

Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen species (ROS), has emerged as a promising approach. Rose Bengal (RB), a xanthene dye, exhibits a high singlet oxygen quantum yield, making it a candidate for aPDT. However, its efficacy in C. albicans treatment has been inconsistent, particularly against biofilm-associated infections, which are more resistant to conventional therapies. This systematic review evaluates the efficacy of Rose Bengal-mediated aPDT in combating C. albicans infections by synthesizing data from studies conducted over the past decade. We focus on the effectiveness of RB across different experimental conditions, including planktonic and biofilm forms of C. albicans. The review also explores the synergy between RB and other agents, such as potassium iodide, and compares the outcomes of RB-mediated aPDT to other photosensitizers and conventional antifungal treatments. Despite its potential, RB-aPDT shows variable effectiveness due to differences in experimental protocols, such as the photosensitizer concentration, incubation times, and light parameters. The review identifies the key limitations, such as RB’s poor biofilm penetration and high dark toxicity at elevated concentrations, which hinder its clinical applicability. The combination of RB with potassium iodide enhances its antifungal efficacy, suggesting that further optimization could improve its clinical potential. Overall, while Rose Bengal-mediated aPDT holds promise as a novel antifungal treatment, further research is needed to standardize protocols, enhance delivery systems, and validate its efficacy in vivo and clinical settings. Full article

Backgrounds and objective: Disorders in the stomatognathic system and otorhinolaryngologic manifestations are frequently observed in individuals living with HIV. Ear, neck, and throat (ENT) signs and symptoms often serve as critical markers of treatment failure, particularly in the advanced stages of HIV infection. This article aims to evaluate and consolidate recent developments in the treatment and management of otorhinolaryngological manifestations in HIV-positive patients. Materials and methods: We carried out a retrospective clinical investigation of patients admitted with HIV/AIDS in the northeastern region of Romania, hospitalized in the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi. We followed the viro-immunological status correlated with patients’ otolaryngology and dental symptomatology, aiming to emphasize the comorbidities of HIV/AIDS cases. The study period spanned from 1 January 2020 to 30 November 2024. Results: There were a total of 552 recorded cases of oropharyngeal manifestations in patients with HIV. They were more frequent in men (358 cases, 64.85%) than women (194 cases, 35.15%). The majority of cases were young adults, aged 30 to 39 years, comprising 255 patients (46.19%), and most cases (36.85%) had CD4+ T-lymphocyte values between 200 and 499 cells/μL. The most frequent diagnosis was oral candidiasis, recorded in 335 male and 174 female cases (509, 92.21% total). Other notable conditions included gingivitis/periodontitis, sinusitis/rhinosinusitis, mastoiditis, and dental abscesses, albeit at lower frequencies. Notably, antifungal therapy with fluconazole was the most frequently employed treatment, followed by aminopenicillins and fluoroquinolones. With respect to the antiretroviral treatment, 83.69% of cases were prescribed a single-pill regimen. Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach, including an ENT specialist and access to antiretroviral therapy. Full article

Background and Objectives: Secondary pulmonary fungal infections in coronavirus disease 2019 (COVID-19) remain underexplored despite emerging reports linking them to heightened morbidity. Comorbidities, steroid use, and prolonged hospital stays can predispose patients to opportunistic fungi. This study aimed to evaluate the impact of fungal coinfection on inflammatory markers, disease severity, antifungal resistance profiles, and outcomes in hospitalized COVID-19 patients. Methods: This retrospective observational study enrolled 280 adults (≥18 years) with real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 admitted to a tertiary care center (January 2023–December 2024). Patients were divided into a COVID-19-only group (n = 216) and a COVID–fungal group (n = 64) based on bronchoalveolar lavage, sputum, and/or blood culture positivity for fungal pathogens. Inflammatory markers (C-reactive protein (CRP), procalcitonin, the neutrophil-to-lymphocyte ratio, and the systemic immune inflammation index) and severity scores (Acute Physiology and Chronic Health Evaluation II, CURB-65 score, and the National Early Warning Score) were measured. We assessed antifungal susceptibilities and recorded ICU admissions, ventilation, hospital length of stay, and mortality. Results: Aspergillus fumigatus (31.3%), Candida albicans (28.1%), Cryptococcus neoformans (7.8%), Pneumocystis jirovecii (6.3%), and Mucorales (6.3%) dominated; Candida glabrata, Candida tropicalis, and mixed infections were also noted. Multidrug-resistant (MDR) isolates or resistance to triazoles occurred in 25.0% of cultures. The COVID-19–fungal group showed significantly higher CRP (85.7 vs. 71.6 mg/L, p < 0.001), procalcitonin (2.4 vs. 1.3 ng/mL, p < 0.001), and APACHE II scores (18.6 vs. 14.8, p < 0.001). intensive-care unit admissions (39.1% vs. 19.9%, p = 0.004) and mechanical ventilation (26.6% vs. 10.2%, p = 0.01) were more frequent with fungal coinfection. Mortality trended at a higher rate (15.6% vs. 7.4%, p = 0.06). Conclusions: Pulmonary fungal coinfections intensify the inflammatory milieu, elevate severity scores, and lead to more frequent ICU-level interventions in COVID-19 patients. Early identification, guided by culture-based and molecular diagnostics, alongside prompt antifungal therapy, could mitigate adverse outcomes. These findings underscore the critical need for proactive fungal surveillance and rigorous stewardship in managing severe COVID-19 pneumonia. Full article

Trichophyton indotineae is associated with difficult-to-treat, often extensive dermatophytosis and resistance to the commonly used antifungal agents. Successful therapy often necessitates higher than usual doses of systemic therapy for prolonged periods. The spread of this species has gained much attention lately, as several European and other Western hemisphere countries have recently reported their first respective cases or increasing numbers of them. Until recently, this species was not described in Hungary. Here, we report a case caused by this species in a patient with a travel history to an endemic region. The isolate was identified preliminarily by MALDI-TOF mass spectrometry and confirmed by DNA sequencing; furthermore, it was subject to phenotypic antifungal susceptibility testing by broth microdilution to fluconazole, voriconazole, posaconazole, itraconazole, and terbinafine. According to the susceptibility results, the isolate was wild type to all tested agents, including terbinafine which was in line with the sequencing data, and with the uncommon excellent therapeutic response to topical allylamine treatment. This case also further confirms the applicability of the MSI-2 database for the rapid identification of T. indotineae in routine clinical microbiology laboratories as a cost-effective and simple method. Full article

Background/Objectives: Mucormycosis is a rare but life-threatening fungal infection, particularly in neonates, due to their undeveloped immune system. This systematic review aims to analyze the risk factors, clinical presentations, treatments, and outcomes of neonatal mucormycosis reported between 2004 and 2024. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science following PRISMA guidelines. Only studies reporting cases of mucormycosis in neonates (≤28 days old) were included. Data on risk factors, clinical features, diagnostic methods, antifungal therapies, surgical interventions, and outcomes were extracted and analyzed. Results: A total of 44 studies met the inclusion criteria, comprising 61 neonatal cases. The most common clinical presentations were gastrointestinal (n = 39), cutaneous (n = 19), rhino-orbito-cerebral (n = 2), and disseminated mucormycosis (n = 1). Diagnosis was primarily based on histopathology (93.4%) and fungal culture (26.2%). The main antifungal treatment was liposomal amphotericin B (63.9%), often combined with surgical debridement (60.6%). Mortality rates remained high (47.5%), particularly in cases of prematurely extreme neonates with angioinvasive disease or delayed diagnosis. Conclusions: Neonatal mucormycosis remains a severe condition with high morbidity and mortality. Early diagnosis through a combination of clinical suspicion and laboratory confirmation, along with prompt antifungal therapy and surgical management, apparently is crucial for improving outcomes. Further studies are needed to optimize treatment strategies and improve neonatal survival. Full article

Candidemia and invasive candidiasis represent critical healthcare-associated fungal infections that pose substantial challenges to medical systems worldwide. These conditions arise when fungi from the Candida genus infiltrate the bloodstream or deeper tissues, leading to a range of clinical manifestations. Among the various species, Candida albicans continues to hold its position as the most frequently encountered causative agent, largely due to its prevalence and adaptability within human hosts. However, it is far from the only significant player; other Candida species, such as Candida glabrata, Candida parapsilosis, and the particularly concerning Candida auris, contribute significantly to the disease burden and exhibit varying dominance depending on geographic regions. The clinical presentation of these infections can differ widely, spanning from subtle, almost imperceptible symptoms in some patients to severe, life-threatening fulminant sepsis in others, often accompanied by alarmingly high mortality rates that underscore the urgency of effective management strategies. Several well-established risk factors predispose individuals to developing invasive candidiasis and candidemia. Breaches in the body’s natural barriers—such as the skin (cutaneous) or the gastrointestinal (GI) tract—provide entry points for these opportunistic pathogens. Additionally, deficiencies in the host’s immune responses, whether due to medical treatments, underlying diseases, or genetic predispositions, heighten vulnerability to infection. Among the diverse Candida species, Candida auris has emerged as an especially troubling entity in recent years. This multidrug-resistant species is notorious for its resistance to standard antifungal therapies, which complicates treatment efforts and contributes to elevated morbidity and mortality rates. Its rapid global spread has positioned it as a formidable public health threat, prompting heightened surveillance and research into its behavior and control. 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