Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor that regulates a spectrum of genes and signalling pathways critical for the antifungal immune response. Mutations in the STAT3 gene confer susceptibility to severe and recurrent fungal infections, predominantly via disruption of interleukin-17 (IL-17)-mediated immunity. This review synthesises current mechanistic insights into STAT3 dysfunction, which impairs the differentiation and effector function of T helper 17 (Th17) cells. This defect results in a profound deficiency of IL-17 and IL-22, which are indispensable for orchestrating antifungal defence at mucosal barriers. The subsequent immunopathological features include impaired neutrophil recruitment to fungal invasion sites, compromised epithelial barrier function and failure to eradicate pathogens such as Candida spp. and Aspergillus spp. Consequently, individuals harbouring STAT3 mutations face a substantially increased risk of disseminated and chronic fungal diseases. Elucidating this STAT3-dependent signalling pathway is essential for deciphering the pathological basis of fungal susceptibility across diverse clinical settings and informing the development of targeted immunotherapies, including immunomodulatory and genetic therapeutic strategies. Additionally, we performed a systematic review of 135 published cases linking STAT3 mutations to fungal infections, aiming to further characterise the role of STAT3 gene defects in fungal susceptibility.

Immunocompromised children with hematologic malignancies or undergoing allogeneic haematopoietic stem cell transplantation (HSCT) are at high risk for invasive fungal diseases (IFDs). Reported incidence varies considerably due to heterogeneous diagnostic criteria, antifungal strategies and environmental conditions. Environmental preventive measures, although highly relevant, remain underrecognised determinants of IFD incidence. This retrospective, single-centre trial included paediatric cancer or transplant patients at high risk for IFD treated before (Cohort 1) and after (Cohort 2) relocation of a paediatric cancer centre from a 1990s building to a state-of-the-art facility with improved environmental protection standards (observation periods: 56 and 12 months, respectively). Antifungal prophylaxis continuously followed local standards. IFD was diagnosed according to 2019 EORTC/MSGERC criteria. Primary endpoint was IFD incidence; secondary endpoints included prophylaxis use, IFD management and mortality. This study included 186 patients (Cohort 1: n = 140; Cohort 2: n = 46). Baseline characteristics were comparable between both cohorts. Adherence to prophylaxis standards exceeded 98%, with liposomal amphotericin B being the most common agent. In Cohort 1, 25 possible, probable, or proven IFD occurred, mainly pulmonary aspergillosis, whereas no cases were observed following implementation of environmental measures in Cohort 2 (17.9% vs. 0%, p = 0.002). Most IFD cases occurred in HSCT recipients. IFD was associated with increased mortality (p < 0.0001). In this contemporary paediatric cancer and transplant setting, environmental protective measures were associated with a marked reduction in IFD incidence, complementing consistent pharmacologic prophylaxis. These findings underscore environmental protection as essential for IFD prevention in high-risk paediatric populations.

ABSTRACTBackgroundDermatophytosis is a common superficial fungal infection that is increasingly complicated by terbinafine (TRB)‐resistant strains, especially Trichophyton indotineae. Conventional antifungals often show limited efficacy against resistant isolates, highlighting the need for novel treatments. This study evaluated the efficacy and safety of nanostructured lipid carrier–loaded luliconazole (NLC‐LCZ) gel in TRB‐resistant dermatophytosis.Materials and MethodsIn a randomized, clinical trial conducted at Touba Specialty Clinic, Sari, Iran, forty‐eight adults with confirmed TRB‐resistant dermatophytosis were assigned to oral itraconazole (ITZ), topical luliconazole, NLC‐LCZ gel, or ITZ + NLC‐LCZ gel for 4 weeks (n = 12 each). The primary endpoint was complete recovery (clinical and mycological), while secondary endpoints included lesion size, itch, inflammation, Dermatology Life Quality Index (DLQI), and safety.ResultsComplete recovery occurred in 83.3% of ITZ + NLC‐LCZ, 75% of NLC‐LCZ, 58.3% of LCZ, and 0% of ITZ alone. LCZ and NLC‐LCZ had lower MIC50/ MIC90 values (0.016 μg/mL) compared with ITZ (MIC90: 8 μg/mL) and TRB (MIC90: 4 μg/mL). DLQI improved most in NLC‐LCZ (score: 2) and ITZ + NLC‐LCZ (score: 3) groups (p < 0.001). Adverse events were mild and did not require discontinuation.ConclusionsThese findings indicate that NLC‐LCZ enhanced antifungal efficacy and quality of life in TRB‐resistant dermatophytosis, and that combination therapy with ITZ + NLC‐LCZ yielded the highest recovery, representing a promising strategy against resistant infections.

Previous research indicated that physicians possess limited knowledge of the diagnosis and treatment of invasive fungal disease (IFD). This study aimed to assess the efficacy of training via video or PDF formats in increasing physicians' knowledge of IFD. This was a multicentre, cluster-randomised controlled trial involving 18 tertiary hospitals in China. Physicians specialising in IFD clinical diagnosis and treatment from four departments were randomised 1:1 into a video training group or PDF training group, and questionnaires were completed before and after training. The primary outcome was the change in total questionnaire score before and after training. Of the 294 participants, 146 were assigned to the video group and 148 to the PDF group. Engagement with the training materials was observed among 127 participants from the video group and 135 from the PDF group. In the per-protocol set (PPS), post-training score improvements for total scores (p = 0.008), invasive candidiasis scores (p < 0.001), and invasive aspergillosis scores (p = 0.044) in the video group were significantly greater than those in the PDF group. Overall, 161 (61.5%) physicians in the PPS exhibited enhanced total scores post-training, with the video group outperforming the PDF group (70.9% vs. 52.6%, p = 0.002). The findings in the FAS were largely consistent with those observed in the PPS. Both video and PDF training modules are appealing to physicians. Further, the video training module displayed superior efficacy in improving physicians' knowledge of IFD.

ABSTRACTBackgroundInvasive pulmonary fungal infections (IPFIs) in immunocompromised children carry high morbidity and may interrupt life‐saving chemotherapy or haematopoietic stem cell transplantation (HSCT). Evidence on perioperative risk stratification for surgical management is limited.Patients and MethodsWe conducted a single‐center retrospective cohort study of patients < 16 years with proven/probable IPFI who underwent lung resection from 2017 to 2025, with fungal infection confirmed by pathology. Preoperative clinical variables, laboratory tests and CT features were collected. Outcomes included intraoperative blood transfusion, severe postoperative complications, 90‐day mortality and time to resumption of chemotherapy/HSCT. An exploratory preoperative weighted risk score was derived and evaluated.ResultsThirty‐three patients were included (median age 9 years; 75.8% male). Aspergillus was the most common pathogen (72.7%); 57.6% had centrally located lesions and 12.1% had multilobe involvement. Procedures were mainly lobectomy (66.7%) or wedge resection (30.3%), with VATS in 45.5%. Peripheral lesion location was associated with less intraoperative transfusion, while hemoptysis and central lesion predicted delayed resumption of chemotherapy/HSCT; preoperative platelet count < 100 × 109/L, multilobe involvement and central location were significantly associated with severe complications. Integrating these independent findings, a 0–8 point composite risk score was constructed (optimism‐adjusted C‐index: 0.948). The model effectively stratified outcomes: severe complications occurred in 0% (low), 26.7% (moderate) and 75% (high) (p = 0.004). Among survivors, median time to resume chemotherapy/HSCT was 18 days (low) versus 35 days (moderate) versus 78 days (high) (p < 0.001). All 90‐day deaths occurred in the high‐risk group (p < 0.001).ConclusionsSurgery can support source control and timely oncologic treatment in selected paediatric IPFI. A simple, statistically validated preoperative score may help anticipate surgical risk and recovery time and identify a high‐risk subgroup with poor short‐term outcomes.

ABSTRACTBackgroundChronic and recalcitrant dermatophytosis has become increasingly problematic in dermatology practice, largely due to emerging antifungal resistance, affecting not only terbinafine but also azoles. Among the causative agents, Trichophyton indotineae has emerged as a key pathogen associated with treatment failure, extensive disease, and frequent relapse, even in immunocompetent patients.ObjectiveThis study aimed to evaluate and compare two rapid molecular diagnostic approaches: A commercial multiplex qPCR assay (DermaGenius Resistance Multiplex PCR, DermaGenius RMP) and a T. indotineae‐specific in‐house qPCR assay, focusing on their practical value for early detection of recalcitrant dermatophyte infections and terbinafine resistance in routine dermatology practice.MethodsSixty‐four dermatophyte isolates obtained from patients with chronic or treatment‐resistant dermatophytosis in Türkiye wereanalysed. Species identification and detection of squalene epoxidase (SQLE) gene mutations associated with terbinafine resistance were performed using DermaGenius RMP and the in‐house T. indotineae‐specific qPCR assay, with confirmatory ITS/SQLE sequencing and CLSI microbroth dilution antifungal susceptibility testing.ResultsOverall concordance between the two qPCR methods was 93.8% (κ = 0.74, z = 5.99, p < 0.001) for T. indotineae identification. Most recalcitrant cases were caused by T. indotineae, and SQLE mutations were detected in > 90% of these isolates, consistent with the observed clinical resistance. DermaGenius RMP enabled rapid, standardised detection of terbinafine resistance–associated mutations suitable for routine diagnostics, whereas the in‐house qPCR provided highly specific identification of T. indotineae. Notably, 10 T. indotineae isolates harboured the SQLE F397L substitution despite terbinafine susceptibility.ConclusionsRapid molecular diagnostics, particularly qPCR‐based assays, provide actionable information early in the course of infection. In this study, both assays showed comparable performance for T. indotineae detection. Prompt identification of T. indotineae and associated resistance mutations may help avoid ineffective antifungal therapy, reduce chronicity, and support rational treatment decisions in routine clinical practice.

ABSTRACTBackgroundThe emergence of Trichophyton indotineae as a multidrug‐resistant dermatophyte has challenged conventional therapeutic approaches for dermatophytosis, leading to a significant therapeutic dilemma. The absence of formal epidemiological cutoff values (ECVs) under the Clinical and Laboratory Standards Institute (CLSI) framework has led to inconsistent interpretation of antifungal susceptibility testing (AFST) data, highlighting the urgent need for standardised susceptibility interpretation criteria and effective therapeutic strategies.ObjectivesThis study aimed to (1) establish CLSI‐based estimated tentative ECVs (ET‐ECVs) to facilitate reliable minimum inhibitory concentration (MIC) interpretation; (2) analyse resistance rates of T. indotineae to terbinafine, itraconazole and voriconazole using a large‐scale global dataset and (3) explore and identify effective therapeutic options following first‐line treatment failure.MethodsThis systematic review compiled global susceptibility data for T. indotineae through comprehensive literature searches, including only studies that performed CLSI‐ or European Committee on Antimicrobial Susceptibility Testing (EUCAST)‐standardised AFST. Furthermore, the clinical efficacy of voriconazole was specifically evaluated by summarising and analysing reported treatment cases.ResultsA total of 67 studies from 14 countries, comprising 981 isolates, were included. The proposed CLSI ET‐ECVs for terbinafine, itraconazole and voriconazole were 0.125, 0.25 and 1 mg/L, respectively, showing full alignment with EUCAST tentative epidemiological cutoff values (TECOFFs). Integrated resistance rates were 77.6% for terbinafine, 17.0% for itraconazole and 1.4% for voriconazole. Cross‐resistance analysis revealed that terbinafine resistance predominated, with 14.3% of isolates co‐resistant to itraconazole. In vitro susceptibility data demonstrated high activity of voriconazole and clinical case summaries further confirmed its favourable therapeutic efficacy, with complete remission reported in all evaluated cases.ConclusionThis study defined the CLSI ET‐ECVs for interpreting T. indotineae MICs, highlighted the resistance burden to first‐line agents and provided in vitro evidence supporting further evaluation of voriconazole as a potential effective alternative therapy. These findings may provide critical warnings regarding the high‐resistance landscape and help guide antifungal susceptibility interpretation for this emerging multidrug‐resistant pathogen.

The incidence of Candida tropicalis isolation is increasing in hospital settings. High azole resistance and mortality rates make it a pathogen that requires further analysis. Fourteen azole resistant Candida glabrata clinical isolates were collected from a Lebanese hospital and analysed through whole genome sequencing for single nucleotide polymorphisms in key resistance and virulence genes, and for phylogenetic relatedness. Isolates were then characterised for pathogenicity related attributes. All isolates had Lys314Glu mutation in ERG20 with multiple isolates displaying numerous shared mutations, such as Glu291Lys in CDR2 and Ala16Thr in CDR3. With the exception of two isolates that clustered together, most isolates were over 99.6% identical based on a genomic heatmap, implying high relatedness consistent with localised clonal expansion, although SNP differences appeared too high to support this. However, the isolates exhibited increased ergosterol and chitin content, as well as upregulation of drug efflux pumps resulting in drug resistance. Our hospital isolates showed convergent resistant pathways, with many isolates having both shared and unique mutations and a high degree of genomic similarities.

ABSTRACTBackgroundTinea capitis (TC) presents with diverse clinical manifestations that may complicate diagnosis. Dermoscopy is a useful adjunctive tool, but data correlating dermoscopic findings with clinical and mycological characteristics in Korean patients remain limited.ObjectiveTo characterize dermoscopic features of TC in Korean patients and evaluate their associations with clinical subtypes, age distributions and causative dermatophytes.MethodsWe retrospectively analysed 71 patients with mycologically confirmed TC diagnosed between 2011 and 2025. Dermoscopic patterns were compared across clinical subtypes, fungal species and age groups. Representative dystrophic hairs were further examined using super‐resolution confocal laser scanning microscopy.ResultsThe cohort demonstrated a bimodal age distribution, with peaks in children (≤ 10 years) and elderly adults (≥ 61 years). Microsporum canis was the predominant pathogen (71.8%). The most frequent dermoscopic findings were scaling (83.1%), black dots (78.9%), follicular hyperkeratosis (78.9%) and broken hairs (78.9%). Empty follicles were significantly associated with Trichophyton infections (p = 0.001), whereas zigzag hairs, Morse code–like hairs, bent hairs and scaling were significantly more frequent in Microsporum infections (p < 0.05). Comma hairs were commonly observed in diffuse pustular and black dot subtypes. Children more often exhibited Morse code–like hairs, whereas elderly patients showed higher rates of empty follicles and perifollicular erythema. Confocal microscopy confirmed distinct structural shaft damage corresponding to characteristic dermoscopic patterns.ConclusionDermoscopy provides valuable diagnostic and aetiological clues in TC, enabling differentiation between clinical subtypes and prediction of causative fungal species. These findings are especially relevant in adult‐predominant, Microsporum‐endemic settings and support dermoscopy as an important adjunct to routine clinical evaluation.