Search Results (280)

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi—particularly Cryptococcus neoformans and Candida spp., including C. auris—as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections. Full article

Background/Objectives: Invasive pulmonary aspergillosis (IPA) represents a critical respiratory condition mainly caused by Aspergillus fumigatus and other ubiquitous species such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. IPA clinical management has been complicated by diagnostic challenges and therapeutic difficulties due to antifungal intrinsic or secondary resistance episodes. Despite this assumption, few scientific data have been reported about possible antifungal drug combinations. Herein, we propose an experimental evaluation using isavuconazole/amphotericin B and isavuconazole/caspofungin in vitro synergy assays to investigate their combined activity on Aspergillus spp. IPA clinical isolates. Methods: We globally analyzed 55 Aspergillus spp. isolates, practicing the gradient test methods with single and combined antifungal drugs through the MIC Strip test (Liofilchem, Roseto degli Abruzzi, Italy). The collected MIC values were interpreted according to the EUCAST guidelines and classified as synergy, additivity, indifference, and antagonism cases through a FIC index calculation. A statistical analysis on species’ correlation with particular synergy testing results was finally provided. Results: Despite an interesting activity against A. fumigatus, isavuconazole/amphotericin B did not report statistical significance, obtaining a consistent antagonism percentage (43.6%). On the other hand, isavuconazole/caspofungin showed a promising in vitro synergic activity, except for A. flavus isolates. Conclusions: Synergy testing demonstrated a significant species-specific trend. Future studies should be focused on Aspergillus spp. isolates and antifungal in vitro synergy testing, aiming to discourage or recommend any specific antifungal combinations, depending on the isolated species. Full article

Candida auris has emerged as a global public health threat due to its high mortality rates, multidrug resistance, and rapid transmission in healthcare settings. This study reports the first documented cases of C. auris candidemia in Portugal, comprising eight isolates from candidemia and colonised patients admitted to a major hospital in northern Portugal in 2023. Whole-genome sequencing (WGS) was performed to determine the phylogenetic relationships of the isolates, which were classified as belonging to Clade I. Genome sequencing also enabled the detection of missense mutations in antifungal resistance genes, which were correlated with antifungal susceptibility profiles determined according to EUCAST (European Committee on Antimicrobial Susceptibility Test) protocols and guidelines. All isolates exhibited resistance to fluconazole and amphotericin B according to the recently established EUCAST epidemiological cut-offs (ECOFFs). Most of the isolates showed a resistant phenotype to anidulafungin and micafungin. All isolates were resistant to caspofungin. Missense mutations identified included Y132F in ERG11, E709D in CDR1, A583S in TAC1b, K52N and E1464K in SNQ2, K74E in CIS2, M192I in ERG4, a novel mutation S237T in CRZ1, and variants in GCN5, a gene involved in chromatin remodelling and stress-response regulation. Identifying known and novel mutations highlights the evolution of antifungal resistance mechanisms in C. auris. These findings underscore the need for further research to understand C. auris resistance pathways and to guide effective clinical management strategies. Full article

Dermatophytes are highly infectious pathogenic fungi that colonize keratinized tissues like skin, hair, and nails, causing superficial infections such as tinea capitis, onychomycosis, tinea corporis, and tinea pedis in humans and animals. In immunocompromised patients, they may invade deeper tissues and organs, leading to severe or life-threatening conditions if untreated or inadequately managed. While most infections respond to topical antifungals, some require complex treatment and show resistance to standard therapies. Therefore, novel antifungal agents are needed. We investigated the antidermatophytic activity of imidazole-thiosemicarbazides against Microsporum canis, Trichophyton spp., and Chrysosporium spp. using the broth microdilution method, comparing results to ketoconazole and amphotericin B through minimal inhibitory concentration (MIC), half-maximal inhibitory concentration (IC₅₀), and selectivity index (SI). Iodine- and bromine-substituted compounds showed the strongest activity, with MICs of 15.15 (IC₅₀ < 1 μM; SI > 213) and 73.46 μg/mL (IC₅₀ < 1 μM; SI > 846) against T. tonsurans, and 3.87 (IC₅₀ = 7.21 μM; SI > 29.6) and 7.38 μg/mL (IC₅₀ = 11.06 μM; SI = 76.6) against M. canis. In silico analysis revealed interactions with α-keratin and lanosterol-14-α demethylase (the azole target enzyme), suggesting enhanced drug retention and action. These findings support these compounds as promising leads for further antifungal development. Full article

(1) Background: Fungal infections of amniotic fluid, especially those caused by Candida spp., are rare but clinically important, as they can be correlated with preterm birth and poor neonatal outcomes. The aim of this study was to assess the antifungal susceptibility of Candida spp. isolated from amniotic fluid using an MIC (minimum inhibitory concentration)-based assay. (2) Methods: Forty consecutive, exploratory Candida isolates were identified from amniotic fluid samples at the “Cuza Vodă” Clinical Hospital of Obstetrics and Gynecology, Iași, and were analyzed successively using Sabouraud agar, the VITEK^® 2 Compact system, and real-time PCR (RT-PCR). (3) Results: C. albicans was the most abundant species (67.5%), followed by Pichia kudriavzevii, Nakaseomyces glabratus, C. parapsilosis, and C. dubliniensis. Fluconazole resistance was observed in two C. albicans isolates, emphasizing the clinical importance of routine antifungal susceptibility testing, and all C. albicans isolates were resistant to micafungin, while amphotericin B remained effective against all isolates. RT-PCR confirmed the presence of C. albicans DNA. (4) Conclusions: The detection of resistant Candida strains highlights the importance of conducting assessments at the species level, which could help clinicians to ensure better antifungal stewardship. Full article

Invasive infections caused by rare moulds (RM) are increasingly reported and often exhibit resistance to antifungal agents. Their epidemiology varies regionally, yet data from Greece are scarce. To address this gap, we conducted a 15-year retrospective study of RM fungaemia at a tertiary academic hospital in Athens, Greece. All microbiologically confirmed cases in hospitalised patients between 2010 and 2024 were reviewed. Demographic and clinical data were retrieved from medical records. Incidence rates were calculated per 1000 admissions and 10,000 bed-days. Isolates were morphologically identified and, when available, molecularly characterised and tested for antifungal susceptibility according to EUCAST guidelines. Eight RM fungaemia episodes (0.8% of total fungaemias) were identified, with an incidence of 0.01/1000 admissions and 0.03/10,000 bed-days, without bacterial co-infections. Haematological malignancies (62%) were the most common underlying condition. Fusarium spp. were the predominant pathogens (6/8), followed by single cases due to Lomentospora prolificans and Acremonium spp. Amphotericin B showed the highest in vitro activity against Fusarium isolates (MIC 0.5–1 mg/L), followed by voriconazole (MICs 2–8 mg/L) whereas other azoles showed no in vitro activity (MICs ≥ 8 mg/L). Half of the infections were breakthrough, whereas in 3/8 cases, the diagnosis was established post-mortem (n = 2) or post-discharge. Among the five patients who received treatment, the crude mortality rate was 60%. This first epidemiological report on RM fungaemia in Greece highlights the predominance of Fusarium spp., the frequency of breakthrough infections, and the challenges in early diagnosis and management. Increased clinical awareness and regional surveillance are essential for optimising outcomes. Full article

Aspergillus fumigatus is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host’s immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by A. fumigatus increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against A. fumigatus. In both assays, metabolically active A. fumigatus biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against Aspergillus biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings. Full article

Background: Oral candidiasis is a prevalent opportunistic infection, predominantly caused by Candida albicans (CA), though non-albicans Candida (NAC) species are increasing worldwide. This study aimed to characterize the prevalence of Candida species, evaluate antifungal susceptibility, and identify predisposing risk factors in patients with oral mucosal candidiasis. Methods: A retrospective review of 1286 electronic patient medical records (788 women, 498 men) from 2018 to 2022 was conducted at the Department of Periodontal and Oral Mucosa Diseases, Medical University of Silesia. Swabs from the oral cavity were processed to identify Candida strains by mass spectrometry, followed by drug susceptibility testing for amphotericin B, nystatin, flucytosine, econazole, ketoconazole, miconazole, and fluconazole. Relevant local and systemic predisposing factors were recorded and analyzed statistically. Results: Among 958 patients with positive fungal cultures, CA accounted for 66.79% of isolates, while NAC constituted 33.21%. Multi-strain infections were detected in 8.46% of patients. CA showed lower resistance (<10%) to amphotericin B, nystatin, and flucytosine, but up to 30% resistance to azoles. NAC strains demonstrated elevated resistance rates (>40% for most azoles), with C. krusei exhibiting the highest resistance to the previously mentioned antifungal agents. Key risk factors included wearing removable dentures (p = 0.042) and uncontrolled diabetes mellitus (p = 0.0431). Additional factors, including poor oral hygiene, reduced salivary flow, and immunosuppressive conditions, further increased infection risk. Patients presenting with multiple risk factors were more likely to have multi-strain infections and more severe disease courses. Conclusions: This retrospective analysis highlights the growing prevalence of NAC, rising antifungal resistance (particularly to azoles), and the importance of identifying risk factors, especially denture use and poor glycemic control. Enhanced preventive strategies, robust diagnostic approaches, and optimized antifungal regimens are essential to address this evolving clinical challenge. Full article

The research aimed to study the genome of Cryptococcus neoformans isolated from bird excreta. Thirteen isolates were cultured, colony stained, and underwent biochemical testing confirmation by nested polymerase chain reaction using ITS1-ITS4 and CN4-CN5 primers, respectively. Antifungal susceptibility testing and whole-genomic sequencing were analyzed. The results determined that all isolates were susceptible to amphotericin B (100%), fluconazole, and itraconazole (92.3%). One isolate (DOP3) showed resistance to fluconazole and itraconazole (MIC >64 and >8 µg/mL, respectively). A phylogenetic tree showed the identity of C. neoformans (serotype A). The genome of resistant (DOP3) and non-resistant isolates (DOP3.1) had 14 chromosomes. DOP3 consisted of 38 candidate antifungal resistance genes, which were the most active against azoles (14). The annotated genes in the azole group mostly were in the ATP-binding cassette transporter transmembrane superfamily. Resistance genes against FCZ were in the transcription factors (HAP2, HAP5), zinc finger (NRG1), cytochrome P450 (ERG11), and Myb-like DNA-binding domain (REB1). The most frequent resistance genes against ITZ were cytochrome P450 (ERG5 and ERG11) and a transcription factor (HAP5). DOP3.1 also consisted of 26 candidate resistance genes against azoles. Resistance genes against the azole group belong to the ABC transporter transmembrane superfamily. Resistance genes against FCZ belong to cytochrome P450 (ERG11), the zinc finger (NRG1), and the CCAAT binding transcription factor (HAP2). Resistance genes belonging to cytochrome P450 (ERG5) were found against ITZ. This research provides the first report of C. neoformans (serotype A) in zebra dove excreta, drug susceptibility to a resistant strain, and identification of resistance genes. Farm sanitation should be strictly applied, and immunocompetent people should avoid contact with zebra dove excreta. Full article

Candida albicans and Candida glabrata are key fungal pathogens linked to candidiasis, with rising concerns due to antifungal resistance and biofilm abilities. However, data from Latin America remains limited. This study assessed biofilm formation and antifungal susceptibility of vaginal Candida isolates from Ecuadorian women. Biofilm formation at 24 and 48 h was evaluated using biomass and CFU assays and the biofilm formation index. Antifungal resistance in planktonic cells and patient microbiota profiles were also analyzed. Biofilm assessment showed 57.14% of isolates were high biofilm formers, 33.33% intermediate, 4.76% low, and 4.76% non-formers. Planktonic susceptibility testing included fluconazole, voriconazole, posaconazole, caspofungin, anidulafungin, micafungin, flucytosine, and amphotericin B. Micafungin showed the lowest MBEC90 value among tested antifungals, with an average MIC of 0.15 µg/mL, MBIC90 of 1.26 µg/mL, and MBEC90 of 1.86 µg/mL. Fluconazole followed with MIC, MBIC90, and MBEC90 values of 4.19, 63.33, and 66.59 µg/mL. Flucytosine had the highest values (MIC = 11.36 µg/mL; MBIC90 = 244.71 µg/mL; MBEC90 = 245.33 µg/mL). Both micafungin and flucytosine produced similar reductions in viable biofilm cells (1.44 log CFU), while fluconazole induced a slightly lower reduction of 1.39 log CFU. Findings suggest echinocandins may be effective against biofilm-forming Candida in this Ecuadorian population subset. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

Background: Scedosporium apiospermum is a filamentous fungus increasingly recognized as an opportunistic pathogen in immunocompromised hosts, though rare infections in immunocompetent individuals with structural lung disease have been reported. Its diagnosis and management remain challenging due to non-specific clinical presentation and intrinsic resistance to multiple antifungal agents. Case Presentation: We report the case of a 66-year-old immunocompetent woman with idiopathic bilateral non-cystic fibrosis bronchiectasis, who presented with subacute cough and increased sputum production. Chest high-resolution CT revealed new subsolid and ground-glass infiltrates superimposed on stable bronchiectatic changes. Bronchoalveolar lavage (BAL) cultures isolated S. apiospermum as the sole pathogen. The patient was treated with oral voriconazole (200 mg BID) for 4 weeks, followed by a 4-week course of aerosolized amphotericin B. Clinical and radiological improvement was observed, and no relapse occurred during follow-up. Discussion: This case highlights the potential for S. apiospermum to cause clinically relevant pulmonary infection in structurally abnormal but immunocompetent lungs. Non-CF bronchiectasis may facilitate fungal colonization due to impaired mucociliary clearance and chronic mucus retention. Combined antifungal therapy involving systemic voriconazole and inhaled amphotericin B (though not yet standardized) was employed based on clinical rationale and the available literature, resulting in favorable outcomes. Conclusions:S. apiospermum pulmonary infection, although rare in immunocompetent hosts with bronchiectasis, should be considered in cases of new or persistent infiltrates. Early recognition and individualized antifungal strategies, including the potential role of inhaled agents, may improve clinical outcomes. This case reinforces the importance of multidisciplinary collaboration in the management of complex fungal infections in chronic airway disease. Full article

This study aimed to systematically evaluate the resistance rates of Candida albicans to various antifungals based on studies conducted in Türkiye and published between 2005 and 2025 and to analyze the factors contributing to resistance. A systematic literature search was conducted using various keywords in electronic databases (PubMed, Embase, Web of Science, EBSCO, Scopus, Turk Medline and Google Scholar). A total of 42 studies were included in the meta-analysis according to the determined criteria. The quality of the studies was assessed using the Joanna Briggs Institute checklist, and the analyses were performed using appropriate statistical software. The highest resistance rates for fluconazole, itraconazole, and voriconazole were observed in the Aegean and Marmara regions. In the analyses performed with the random-effects model, heterogeneity was found to be high for itraconazole, fluconazole, posaconazole, voriconazole, and caspofungin, and the strongest explanatory variable of this heterogeneity was the geographical region variable. In our study, we determined that antifungal resistance in C. albicans strains in Türkiye is generally low; however, an increasing trend has been observed over the years, especially in amphotericin B resistance. Although the low resistance rates to major antifungal agents such as fluconazole, voriconazole and echinocandins are promising, regional differences and methodological heterogeneity necessitate the development of treatment strategies based on local data. Full article

Background: First-line treatments for cutaneous leishmaniasis (CL), including topical agents, are often limited in cases of complicated disease involving multiple, facial, or treatment-resistant lesions. Data on intravenous liposomal amphotericin B (L-AmB) are scarce, especially in children. We report our experience using L-AmB to treat pediatric CL, focusing on treatment rationale, safety, and clinical effectiveness. Methods: A retrospective case series. Diagnosis was confirmed by PCR. Data on demographics, clinical presentation, treatment rationale, adverse events, lab findings, and outcomes, during treatment and follow-up, were collected. Results: Twenty-seven children were included, most (96%) with Leishmania major. The mean number of lesions per child was 5.71 ± 6.19. All had facial involvement; 41% nasal and 15% eyelid. Most lesions were ulcerated (78%). Prior treatment failure was common (78%), with the use of topical antimicrobials, liposomal amphotericin gel, and paromomycin-containing ointments (59%, 38%, 19%, respectively). Twenty-four children (89%) completed treatment successfully. Adverse events occurred in 41% of cases but were mostly mild and reversible: flushing, rash, shortness of breath, and vomiting (11%, each). One case of transient renal impairment and one case with neutropenia were recorded. Early improvement was noted by day 10, with 50% (n = 12) of cases exhibiting crust falling/reduced ulceration and a 50% lesion size reduction. By day 30–90, 92% achieved substantial healing without the need for further therapy. Nevertheless, scarring was noted in 79% of cases. Conclusions: L-AmB treatment appears to be safe and effective for pediatric CL, particularly in cases with facial lesions or prior treatment failure. Clinical improvement was notable, although scarring was common. Full article

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