In a pilot study of 12 patients with chronic productive cough, we retrospectively compared sputum viscoelasticity before macrolide antibiotic administration and the clinical effects of macrolide antibiotic administration between two groups with and without sputum fungal culture. The fungal culture-positive group (n = 6) showed significantly higher sputum rheological parameters in the high-strain region, particularly critical strain (γC), and reduced response to macrolide treatment. In 5 patients with fungus-associated chronic cough, a decrease in high-strain sputum viscoelasticity and improvement in cough and laryngeal abnormal sensations were observed after administration of low-dose antifungals.
An adlescent girl was bitten on the right middle finger while attempting to intervene in a fight among her three pet guinea pigs. She was initially treated by a local physician without improvement and was subsequently referred to the Department of Dermatology at our hospital. Direct microscopic examination of scales and crusts with KOH was positive, and she was diagnosed with tinea corporis. The isolated fungus was morphologically identified as belonging to the Trichophyton mentagrophytes complex, and topical luliconazole cream was administered. Molecular analysis based on the DNA sequence of the nuclear ribosomal internal transcribed spacer (ITS) 1 region revealed that the isolate belonged to ITS type II, corresponding to T. mentagrophytes animal type 3. These findings strongly suggested zoonotic transmission from the pet guinea pigs. This appears to be one of the very few reported cases of T. mentagrophytes animal type 3 isolated from a human lesion.
We report a case series evaluating a novel oral care paste containing capric acid and a lysozyme-chitosan oligosaccharide conjugate (LYZOX). Ten patients with asymptomatic oral Candida colonization performed twice-daily self-care. Clinical eradication was achieved in 80% of cases, including polymicrobial infections involving Candida albicans, Candida glabrata, and Candida parapsilosis. This non-pharmacological approach effectively eliminated Candida species without adverse effects, suggesting a safe, daily preventive strategy for asymptomatic carriers in the maintenance phase of dental treatment.
Aspergillus fumigatus strains cause severe mycosis in humans. Strains belonging to the cryptic species of A. fumigatus, such as Aspergillus lentulus, are also pathogenic and tend to exhibit resistance to azole drugs. Although the contribution of cytochrome P450 14-α sterol demethylase (Cyp51A) to azole resistance in A. lentulus has been highlighted, the molecular mechanisms behind it remain unknown. In this study, we performed functional analysis of the CYP51 gene derived from A. lentulus (Al-cyp51A) to identify substitutions affecting azole susceptibility. We constructed a CRISPR/Cas9-based genome editing method that enabled one-step replacement of the cyp51A locus in A. fumigatus. Using this system showed that the expression of Al-cyp51A in the A. fumigatus strain increased its resistance to voriconazole (VRCZ) in comparison with the cyp51A of A. fumigatus (Af-cyp51A). By screening chimeric Al-cyp51A harboring partial sequences of Af-cyp51A, we successfully identified amino acid residues in Al-Cyp51A that contributed to VRCZ resistance. Molecular dynamics simulations showed that these substitutions may reduce the inhibitory effect of the drug. Our findings provide further insights into the molecular mechanisms of azole resistance in cryptic A. fumigatus and highlight the functional role of cyp51A mutations.
A male in his seventies presented with multiple erythematous follicular papules on the back, followed by lesions in the occipital region and posterior neck. Fungal examination revealed kerion celsi caused by Trichophyton rubrum. The patient was treated with fosravuconazole 100 mg/day for 8 weeks, and the brush method was negative 1 month later. The oral antifungal medicines approved for treatment of tinea capitis in Japan are limited to itraconazole and terbinafine hydrochloride. However, itraconazole has many contraindicated drugs, and antifungal resistance has recently become a major concern.As the challenge of drug-resistant fungi is expected to become more significant in the future, the clinical benefits of using fosravuconazole L-lysine ethanolate (F-RVCZ) for treating kerion celsi may increase. Our experience suggests that F-RVCZ could be a valuable therapeutic option.
Antifungal susceptibility testing is essential for guiding the clinical management of fungal infections. However, the standard method for broth dilution testing of filamentous fungi requires spore suspensions and is therefore unsuitable for poorly sporulating fungal species or strains. Some Aspergillus lentulus strains sporulate poorly, and Schizophyllum commune is a clinically relevant non-sporulating fungus for which preparing homogeneous inocula remains challenging. In this study, we developed an agar‑based visual assay to evaluate relative growth inhibition without requiring spores. Using 6‑well plates containing varying concentrations of itraconazole (ITCZ) or voriconazole (VRCZ), the colony diameters of A. lentulus and S. commune were measured after 24 hours and 48 hours, respectively, and normalized to those of the drug‑free control. A. lentulus exhibited clear growth inhibition at 0.25 µg/mL ITCZ, but further increases in concentration did not result in proportionally greater inhibition under the present assay conditions. In contrast, VRCZ markedly and dose‑dependently reduced colony diameter, resulting in only < 10% growth at 4 µg/mL. ITCZ susceptibility varied widely among S. commune strains, whereas VRCZ consistently inhibited growth at concentrations ≥ 1 µg/mL. These susceptibility patterns aligned with previously reported minimum inhibitory concentration ranges for both species. Notably, our method also accommodated slow‑growing strains and allowed extended incubation when necessary. Although not directly comparable to standardized minimum inhibitory concentration methods, our agar‑based assay provides a practical and visually interpretable means to assess drug susceptibility in A. lentulus and S. commune under the tested conditions.
With advances in molecular biology, the recognition of fungal species has been revised, and the nomenclature systems themselves have been changed to adopt the "one-fungus-one-name" concept, resulting in the names of many species being changed in recent years. This article provides an overview of recent changes in the names of fungi associated with skin diseases, with a particular focus on Malassezia species, some Trichophyton species including Trichophyton benhamiae and Trichophyton indotineae, along with several species causing deep dermatomycoses.
We describe a male in his fifties with a refractory azole-resistant Candida albicans renal and perirenal walled-off abscess. C. albicans developed acquired azole-resistance during fluconazole (FLCZ) therapy. Despite FLCZ penetrating the walled-off abscess (11.1 μg/g) with levels exceeding those in normal renal tissue, the infection persisted, necessitating nephrectomy. Despite no amino acid substitutions in the ERG11 gene as revealed by genetic analysis, a Rhodamine 6G assay demonstrated a 4.5- to 6.6-fold increase in efflux activity in the resistant isolates in comparison with the susceptible controls, suggesting efflux pump-mediated resistance. Following surgery, the patient developed emphysematous pyelonephritis in the contralateral kidney due to azole-resistant C. albicans. This case demonstrates that even substantial tissue penetration cannot overcome high-level, effluxmediated resistance within walled-off lesions, underscoring the critical importance of surgical source control.
Background: Oral antifungal therapy is the standard treatment for onychomycosis. However, many physicians still prefer topical agents because of concerns about adverse effects. Objectives: This study evaluated changes in hepatic and renal function parameters during fosravuconazole therapy and assessed the utility of an algorithmic approach for interpreting these abnormalities. Methods: Laboratory parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (gamma-GTP), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were compared between baseline and follow-up. Fold changes were calculated, and gamma-GTP was classified according to the LiverTox database. Each parameter was assessed using an algorithm for managing hepatic and renal side effects. Results: A total of 128 cases were analyzed. Median baseline values were AST 22 U/L, ALT 19 U/L, gamma-GTP 25 U/L, sCr 0.75 mg/dL, and eGFR 74.9 mL/min/1.73 m(2). At follow-up, values were AST 22 U/L, ALT 22 U/L, gamma-GTP 51.5 U/L, sCr 0.86 mg/dL, and eGFR 67.1 mL/min/1.73 m(2). gamma-GTP showed significantly greater fold changes than other parameters (p < 0.001). Thresholds for discontinuation were met in 3 hepatic (2.3%) and 5 renal (3.9%) cases. No patient developed clinical symptoms, and only one discontinued treatment. Conclusions: Algorithm-based monitoring enabled safe fosravuconazole administration. This practical approach may help clinicians adopt oral antifungal therapy more confidently as first-line treatment for onychomycosis.
Medical mycology is a traditional field of medicine that has developed over a long history through the contributions of numerous researchers and clinicians. This paper focuses on the most influential individuals, discoveries, and inventions within the field, examining the development of medical mycology from the perspective of a return to its origins, including on-site investigations. This return to origins is not merely a historical retrospective but also an effort to reevaluate and deepen our understanding through practical research, aiming to explore the foundational studies that marked the beginning of medical mycology and its related disciplines. Furthermore, this paper highlights the conceptual meaning of the "light and shadow" of medical mycology. While the field has made substantial progress, it has often been overshadowed by the remarkable achievements of other disciplines, such as botany, symbolized by Linnaeus, and bacteriology, represented by Koch. This study attempts to reassess the history and significance of medical mycology. Additionally, it examines the resurgence of medical mycology and the dramatic paradigm shift triggered by a single publication from the United States. Through these considerations, this paper aims to provide a long-term and multidimensional reexamination of the progress of medical mycology.
BACKGROUND:We compared medication adherence and satisfaction between miconazole mucoadhesive buccal tablets (MBT) and miconazole oral gel (MOG) in patients with oral candidiasis. METHODS:This observational study included patients diagnosed with oral candidiasis and treated with miconazole by our department between June 2021 and August 2024. MBT was prescribed as first-line therapy according to Infectious Diseases Society of America guidelines, whereas MOG was selected when MBT use was anticipated to be difficult (e.g., denture wearers). After approximately 14 days of therapy, patients completed a questionnaire on treatment completion, daily adherence, usability, and satisfaction. Baseline data were extracted from medical records. Statistical comparisons used Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS:Forty-six patients (Age median 77.0 years [IQR: 69.5-80.5], 72% female) were analyzed. Baseline characteristics were comparable between groups. The treatment completion rate was 79% for MOG and 67% for MBT (p = 0.510). Daily adherence was significantly higher in the MBT group (89%) than in the MOG group (53%, p = 0.015). The most frequent reason for non-completion in the MBT group was "easy detachment" of the tablet. Usability was rated as acceptable by approximately 70% of patients in both groups. While median satisfaction scores did not differ significantly, a higher proportion of MBT users reported high satisfaction (≥ 8/10). CONCLUSION:Once-daily MBT may improve daily adherence compared with MOG, particularly in elderly patients receiving multiple medications. However, detachment issues may limit completion rates, highlighting the importance of patient-specific formulation selection and administration strategies.
BACKGROUND:Oral antifungal therapy is the standard treatment for onychomycosis. However, many physicians still prefer topical agents because of concerns about adverse effects. OBJECTIVES:This study evaluated changes in hepatic and renal function parameters during fosravuconazole therapy and assessed the utility of an algorithmic approach for interpreting these abnormalities. METHODS:Laboratory parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ glutamyltransferase (γ-GTP), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were compared between baseline and follow-up. Fold changes were calculated, and γ-GTP was classified according to the LiverTox database. Each parameter was assessed using an algorithm for managing hepatic and renal side effects. RESULTS:A total of 128 cases were analyzed. Median baseline values were AST 22 U/L, ALT 19 U/L, γ-GTP 25 U/L, sCr 0.75 mg/dL, and eGFR 74.9 mL/min/1.73 m². At follow-up, values were AST 22 U/L, ALT 22 U/L, γ-GTP 51.5 U/L, sCr 0.86 mg/dL, and eGFR 67.1 mL/min/1.73 m². γ-GTP showed significantly greater fold changes than other parameters (p < 0.001). Thresholds for discontinuation were met in 3 hepatic (2.3%) and 5 renal (3.9%) cases. No patient developed clinical symptoms, and only one discontinued treatment. CONCLUSIONS:Algorithm-based monitoring enabled safe fosravuconazole administration. This practical approach may help clinicians adopt oral antifungal therapy more confidently as first-line treatment for onychomycosis.
This review summarizes current knowledge on ocular fungal infections, with emphasis on the clinical characteristics, diagnostic approaches, and management of keratitis and endophthalmitis caused by uncommon fungal pathogens. Filamentous fungi such as Fusarium and Aspergillus often cause rapidly progressive disease, whereas Candida species typically infect eyes with preexisting ocular surface abnormalities or systemic risk factors. Diagnosis relies primarily on microscopy and culture, supplemented by molecular techniques where available. Management requires organism-directed antifungal therapy, with surgical intervention reserved for refractory or vision-threatening cases. Despite advances in diagnostic modalities and therapeutics, fungal keratitis and endophthalmitis remain important causes of visual morbidity, underscoring the need for early recognition and appropriate treatment.
Dermatophytosis remains one of the most common superficial fungal infections worldwide, and antifungal-resistant strains have recently emerged as an increasing clinical concern. In Japan, the prevalence of terbinafine-resistant Trichophyton species is currently estimated to be 2%, with most isolates harboring squalene epoxidase (SQLE) gene mutations such as Leu393Phe and Phe397Leu. This review summarizes recent epidemiological findings and representative clinical cases to illustrate the practical management strategies for antifungal-resistant dermatophytosis in Japan. Three illustrative cases were presented. Case 1 involved Trichophyton interdigitale carrying a Phe397Leu mutation that was unresponsive to terbinafine but was successfully treated with topical efinaconazole and luliconazole. Case 2 described a cluster infection of terbinafine-resistant Trichophyton rubrum (Leu393Phe) in a group home, where oral fosravuconazole achieved complete cure. Case 3 reported five soldiers with terbinafine-resistant dermatophytosis caused by Phe397Leu or Phe415Ile mutations, which were likely associated with prolonged topical SQLE inhibitor use. Resistance is often induced by the long-term or intermittent application of SQLE inhibitors, including over-the-counter topical terbinafine and butenafine. For suspected terbinafine-resistant infections, non-SQLE azoles, such as luliconazole and lanoconazole, are recommended because of their 10- to 100-fold increased activity against Trichophyton species. Oral fosravuconazole and topical agents such as 10% efinaconazole or 5% luliconazole have proven effective for onychomycosis. Ongoing surveillance, appropriate antifungal stewardship, and timely adjustment of treatment regimens are essential to prevent the further spread of antifungal-resistant dermatophytosis.
Yeasts show few distinct morphological characteristics. The two basic forms of yeast, unicellular yeast and multicellular hyphal form, exhibit dimorphism. In a recent study on Trichosporon asahii, a dimorphic basidiomycetous yeast that causes trichosporonosis, the addition of magnesium induced hyphal formation and changes in organelle distribution. A detailed observation of organelle distribution revealed that the responses to magnesium addition varied widely among Trichosporonales yeasts. In this review, we show that differences in organelle phenotypes upon magnesium addition possibly contribute to the practical identification and classification of Trichosporonales yeasts.
Azole antifungals are the cornerstone of therapy for aspergillosis, yet the global rise in azole-resistant Aspergillus fumigatus has become a major clinical concern. Resistance rates vary widely across regions, with particularly serious implications for chronic pulmonary aspergillosis (CPA), which requires long-term azole therapy. Resistance mechanisms largely involve cyp51A mutations, although additional genetic alterations and environmental factors, such as agricultural azole use, also play important roles. Cross-resistance among azoles is frequent, leaving clinicians with limited alternatives, such as liposomal amphotericin B or echinocandins, which are constrained by toxicity, fungistatic activity, and intravenous administration. Currently, antifungal susceptibility testing for filamentous fungi remains technically demanding and is not routinely available in many countries, including Japan, further complicating its management. Emerging approaches include the development of novel antifungal compounds and optimization of existing drugs through inhaled or nanoformulated delivery systems. Furthermore, fungal vaccines are attracting increasing attention as promising long-term solutions to stagnant antifungal pipelines and the growing challenge of drug resistance.
