Extensive superficial dermatomycosis caused by Cladophialophora sp., a deep mycosis pathogen: A case report

Barrier Function, Epidermal Differentiation, and Human β-Defensin 2 Expression in Tinea Corporis

Antifungal resistance is a growing concern as it poses a significant threat to public health. Fungal infections are a significant cause of morbidity and mortality, especially in immunocompromised individuals. The limited number of antifungal agents and the emergence of resistance have led to a critical need to understand the mechanisms of antifungal drug resistance. This review provides an overview of the importance of antifungal resistance, the classes of antifungal agents, and their mode of action. It highlights the molecular mechanisms of antifungal drug resistance, including alterations in drug modification, activation, and availability. In addition, the review discusses the response to drugs via the regulation of multidrug efflux systems and antifungal drug-target interactions. We emphasize the importance of understanding the molecular mechanisms of antifungal drug resistance to develop effective strategies to combat the emergence of resistance and highlight the need for continued research to identify new targets for antifungal drug development and explore alternative therapeutic options to overcome resistance. Overall, an understanding of antifungal drug resistance and its mechanisms will be indispensable for the field of antifungal drug development and clinical management of fungal infections.

Background: Superficial fungal infections (SFI) are common skin diseases that were largely simple to treat. However, due to increasing antimicrobial resistance (AMR) of dermatophytes to antifungal drugs, treatment of SFI has become difficult. This study aims to analyze the AMR of dermatophytes and to correlate with the clinical response of antifungal drugs. Methods: A cross‑sectional evaluation was undertaken of 570 consecutive patients with SFI such as tinea corporis, tinea cruris, tinea faciei, and tinea pedis, who were treated with any of the oral antifungal drugs fluconazole, itraconazole and terbinafine. Clinical response was taken within 1 month of stopping the therapy. Microscopic as well as culture and antimicrobial sensitivity analysis were done to characterize and determine the susceptibility of dermatophytes to antifungal drugs aforementioned. Results: Among the 570 patients with SFI, the ratio of male (n=360, 63.16%) to female (n=210, 36.84%) was 1.7:1. The common age group affected by SFI was 31-40 years (27.71%, n=158). The tinea corporis was the most predominant (51.05%) followed by tinea cruris (13.68%). Clinical response analysis showed that the percentage of relapse of SFI after completion of treatment with fluconazole, itraconazole and terbinafine was about 55, 45 and 19, respectively. Culture and antimicrobial sensitivity analysis revealed that the percentage of resistance of dermatophytes from patients of SFI to fluconazole, itraconozole and terbinafine was approximately 70, 55 and 20, respectively. Conclusion: Results reported herein support the notion that the antifungal resistance is evolving in dermatophytes causing SFI, and about 20% dermatophytes are multidrug resistant.

The hidden threat: Unveiling the rise of antifungal drug resistance.

Chapter 11 - Antifungal resistance

Cryptococcus gattii is a fungal pathogen that poses significant threats to human health, affecting both immunocompromised and immunocompetent individuals. Treatment of C. gattii infections typically involves the use of antifungal agents, such as azoles. However, the increasing emergence of antifungal resistance in C. gattii is a growing concern, highlighting the critical need for novel therapeutic strategies. In our previous study, we identified a mitochondrial ATP-binding cassette (ABC) transporter, Atm1, as potentially involved in antifungal resistance in C. gattii through transcriptome sequencing, but its function remains unclear and requires additional confirmation and investigation. In this study, we developed a "suicide" clustered regularlyinterspaced short palindromic repeats-CRISPR-associated protein 9 system in C. gattii, based on the system used in C. neoformans, and successfully validated its functionality by targeting the ADE2 gene. We subsequently generated C. gattii mutants lacking ATM1 and assessed their growth under various stress conditions. Our data suggest that Atm1 is involved in the iron-sulfur cluster biosynthesis process. Besides, disruption of ATM1 resulted in various growth impairments, including reduced stress tolerance, impaired capsule formation, and diminished virulence. Importantly, we observed compromised antifungal drug resistance in the atm1∆ mutant and performed RNA sequencing-based transcriptome analysis and gene ontology analysis with and without antifungal treatment for further investigation. In conclusion, our findings indicate that ATM1 plays a role in iron homeostasis and is critical for antifungal resistance in C. gattii, offering new insights into potential drug development strategies for the clinical treatment of cryptococcosis.

Background: Dermatomycoses are more prevalent in India due to favourable climatic conditions, poverty, poor hygiene and overcrowding. Sparse published data are available regarding superficial dermatomycoses from India. Methods: In this prospective study, demographic characteristics, clinical spectrum and risk factors for the development were studied in 198 patients with superficial dermatomycoses. Results: Their mean age was 34.1 ± 15.3 years; there were 108 (54.5%) males. Majority of the patients (50.5%) belonged to upper-lower socio-economic status (Class IV as per modified Kuppuswamy's classification). Most of the patients (69.7%) had presented with dermatophytoses. Among superficial dermatomycoses, tinea corporis was the most common (29.3%) clinical type. Potassium hydroxide mount was positive in 77.7% and culture was positive in 30.8%. Trichophyton rubrum was the most common species isolated (64%). Multivariable analysis using logistic regression revealed older age (> 50 years) to be an independent predictor for the development of tinea corporis (p<0.001). Conclusions: Our observations suggest that superficial dermatomycoses are an important cause of morbidity and should be carefully searched for especially in the elderly so that effective curative treatment can be instituted.

Dermatophytosis, particularly tinea corporis and tinea cruris, is a frequent superficial fungal infection, especially in tropical and humid regions. Conventional antifungal treatments, including topical or oral antifungals, may cause side effects, especially with long-term use. Increasing cases of recurrent dermatophytosis and antifungal resistance have prompted the exploration of alternative, safer treatment options. The study aims to evaluate the effectiveness of individualized homeopathic medicines (IHMs) for the treatment of tinea corporis and cruris. The study was conducted at four Homeopathy Outpatient Departments from August 2021 to March 2024. Patients with clinically diagnosed tinea corporis or cruris, confirmed by positive potassium hydroxide (KOH) mount test, were included. IHMs were prescribed based on symptom totality and repertorization. The primary outcome was assessed using a Clinical Cure Scale, which evaluates lesion's resolution, itching, and infection clearance. Mycological assessment was conducted to detect the presence or absence of fungus. The Skindex-16 questionnaire measured the impact of skin disease on quality of life (QoL). Assessments were performed at baseline and monthly, until resolution or for up to six months. A total of 147 patients (mean age of 38.92±12.09 years) were analyzed. Tinea corporis was most prevalent (47%), followed by mixed tinea corporis and cruris (30%) and tinea cruris (23%). After six months, statistically significant improvements were observed in Clinical Cure Scale scores (7.01±1.73 to 2.90±2.66, P < .001) and Skindex-16 scores (from 56.04±25.34 to 27.03±28.99, P < .001). 93 patients (63.3%) tested KOH-negative at the end of treatment. Commonly prescribed medicines included Sulphur (35%), Natrum muriaticum (24%), Sepia (13%), Arsenicum album (11%), Lycopodium clavatum (4%), and Graphites (3%). The findings support the effectiveness of IHMs in managing dermatophytosis. Rigorous clinical and QoL assessments confirm therapeutic benefits. Future randomized controlled trials and long-term follow-up are recommended to validate these results and assess recurrence. tinea corporis, tinea cruris, KOH mount, Skindex-16, homeopathy.

India faces a significant burden of respiratory fungal infections, yet many cases remain underdiagnosed particularly in rural and remote areas. This leads to higher morbidity and mortality rates, especially among immunocompromised individuals. The unique environmental conditions of the Himalayan foothills further complicate the detection and management of these infections.This study was conducted in the Department of Microbiology at All India Institute of Medical Sciences, Rishikesh, for a period of 18 months, from October 2022 to March 2024. The aim of the study was to characterise the clinical, risk factors, susceptibility and outcome profile of invasive bronchopulmonary fungal infections among patients attending AIIMS Rishikesh.Out of the total bronchopulmonary fungal Infections (n=61), 85% cases (n=52) were those of invasive aspergillosis due to Aspergillus spp. with the most common species being A. fumigatus (n=36), followed by A. flavus (n=12), A. terreus (n=2), A. glaucus (n=1), A. niger (n=1). Apart from this, pulmonary mucormycosis was seen in 6% (n=4) of the cases, due to Mucor spp. (n=2), Rhizopus arrhizus (n=1) and Lichthemia corymbifera (n=1). 8% (n=5) of the cases of invasive fungal infections due to rarer fungi, Curvularia lunata (n=1), Scedosporium apiospermum (n=1), Fusarium solani (n=1), Bipolaris spp (n=1), and Penicillium spp. (n=1). The most common risk factor was chronic uncontrolled diabetes mellitus (n=24), COPD/Asthma/ILD (n=22), hypertension (n=18), pulmonary tuberculosis (n=15), different malignancies (n=10) and CAD (n=10). Out of the 61 cases, 52% n=32) patients were discharged with follow up, 32% (n=20) patients succumbed to death, 9% (n=6) cases were treated on an outpatient basis and 6% cases(n=3) patients went left against medical advice. 49% (n=30) required ICU stay during the course of treatment. Aspergillus spp were resistant to iatraconazole and caspofungin with high MIC (8-16).Voricoanzole showed lower MICs (0.06-2) and was preferred for the treatment as well.The study's findings on the high prevalence of invasive aspergillosis (85%) align with global and regional studies, which also identify Aspergillus fumigatus as the leading cause of respiratory fungal infections, especially in immunocompromised patients. Like other research, this study highlights emerging antifungal resistance, with high MICs for itraconazole and caspofungin, underscoring the growing preference for voriconazole due to its lower MICs and better efficacy. Additionally, the presence of rarer fungi like Curvularia and Scedosporium suggests regional variations in pathogen distribution, influenced by local environmental factors in the Himalayan foothills, a trend noted in other endemic regions globally.This study provides crucial insights into the epidemiology, clinical characteristics, and outcomes of bronchopulmonary fungal infections in the Himalayan foothills. The high prevalence of invasive aspergillosis and antifungal resistance, underscores the need for vigilant clinical management and robust public health strategies to mitigate the impact of these infections.

BACKGROUND Mycoses are assuming greater significance both in developed and developing countries particularly due to advent of immunosuppressive drugs and diseases. Dermatophytosis is most common type of cutaneous fungal infections seen in man, though in past few decades non-dermatophytes are also assuming importance. Present study is undertaken to know the pattern of dermatophytosis from our region. METHODS An observational study was conducted on 150 samples of patients with complaints of superficial mycoses. Samples were processed for microscopy on potassium hydroxide (KOH) mount and culture on Sabouraud’s dextrose agar (SDA) with and without cycloheximide and chloramphenicol. Any growth was identified by conventional technique. RESULTS One hundred and fifty samples consisting of 86 skin and 64 nails were studied. Most samples were seen in rainy season and males were predominantly affected. Adults from age of 21 - 50 years were most commonly affected. Most common clinical presentation was tinea corporis (70.93 %). In dermatophytic causes, T. mentagrophytes (36.21 %), T. tonsurans (27.59 %) followed by T. rubrum (15.52 %) were common isolates. In non-dermatophytic causes, candida spp. followed by aspergillus spp. were commonest isolates. CONCLUSIONS Tinea corporis is found to be the commonest presentation. Along with dermatophytes, non-dermatophytic fungi are also emerging as the cause of superficial mycoses. In non-dermatophytic fungi, candida is the commonest species, which is now a days showing drug resistance; hence, identification of causative agent is important for correct and prompt treatment. KEY WORDS Dermatophytosis, Non-Dermatophytic Fungi, Dermatophytic Fungi

Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal resistance (AFR) is vastly under-represented in comparison. Given the growing number of vulnerable, immunocompromised individuals, as well as the positive impact global warming has on fungal growth, there is an immediate urgency to tackle fungal disease, and the disturbing rise in AFR. Chromatin structure and gene expression regulation play pivotal roles in the adaptation of fungal species to anti-fungal stress, suggesting a potential therapeutic avenue to tackle AFR. In this review we discuss both the genetic and epigenetic mechanisms by which chromatin structure can dictate AFR mechanisms and will present evidence of how pathogenic yeast, specifically from the Candida genus, modify chromatin structure to promote survival in the presence of anti-fungal drugs. We also discuss the mechanisms by which anti-chromatin therapy, specifically lysine deacetylase inhibitors, influence the acquisition and phenotypic expression of AFR in Candida spp. and their potential as effective adjuvants to mitigate against AFR.

Cutaneous phaeohyphomycosis in an immunocompromised host

Herpes Simplex

ObjectiveThis study explored the correlation between interleukin-1 receptor/Toll-like receptor (IL-1R/TLRs)-mediated inflammatory signaling pathways and the severity of superficial dermatomycosis.MethodsFrom May 2020 to August 2022, 76 patients with superficial dermatomycosis (infected group) and 52 patients without infection (non-infected group) were enrolled. The indicators related to IL-1R/TLRs pathway were analyzed, and the diagnostic value of the combined detection of each index for superficial dermatomycosis and disease severity was analyzed. The correlation between each index and the severity of infection was analyzed.ResultsIL-1β, TLR4, IL-6, and TNF-α in the infected group were higher than those in the non-infected group (P < 0.05). The AUC of IL-1R/TLRs combined detection in the group diagnosed with a superficial dermatomycosis was higher than that of each single detection (P < 0.05). IL-1β, TLR4, IL-6, and TNF-α in the severe group were higher than those in the mild group (P < 0.05). IL-1β, TLR4, IL-6, and TNF-α were positively correlated with the degree of infection (P < 0.05). The AUC of IL-1R/TLRs combined detection was higher than that of each single test (P < 0.05). IL-1β ≥ 2.87 ng/L, TLR4 ≥ 3.12 ng/L, IL-6 ≥ 4.58 ng/L, TNF-α ≥ 70.53 ng/L were the influencing factors of severe superficial dermatomycosis (P < 0.05).ConclusionIL-1R/TLRs pathway is related to the severity of superficial dermatomycosis, and the collective identification of each indicator provides diagnostic insight into infection severity.

Background: Tinea corporis et cruris is a major category of superficial dermatophytosis, forming the bulk of routine dermatology ailments. However, in recent years, an epidemic-like scenario of dermatophytosis has emerged with increased incidence of atypical morphological clinical variants and changing mycological profiles due to steroid abuse, epidemiological shift and antifungal resistance. Aims: This study aims to document the changing clinicomycological profile of dermatophytosis while highlighting the emerging incidence of varied atypical morphological variants. Methods: A cross-sectional study of cases presenting to the outpatient department with tinea corporis et cruris. Detailed history-taking and clinical examination were followed by direct microscopic examination of skin scrapings in potassium hydroxide (KOH) and fungal culture in Sabouraud’s Dextrose Agar (SDA). Results: One hundred cases were enrolled over a period of 6 months. Male: female ratio observed was 1.56:1. Most patients (51%) had chronic disease, 42% cases showed recurrence, and relapse was seen in 28%; 58% had a history of prior treatment, among which 81.03% had a history of steroid application. Classical tinea corporis et cruris was the most common clinical presentation (54%) with variable degrees of inflammation, followed by steroid-modified tinea (32%), atypical tinea, concomitant bacterial infection, Majocchi’s granuloma, and Erythrodermic dermatophytosis. Atypical emerging morphological variants included tinea pseudoimbricata, double-edged tinea, eczema-like variant, dumbbell-shaped tinea, tinea recidivans, and impetigo-like variant. Lesions were most commonly located on the trunk (83%); unusual anatomical sites involved were ears (12%), eyelids (9%), and glabrous scalp (5%). KOH mount was positive in 68% cases, while fungal culture was positive in 43%. Fungal isolates were Trichophyton mentagrophytes/interdigitale (88.4%), Trichophyton rubrum (6.9%), and Epidermophyton floccosum (4.6%). Conclusion: The changing clinicomycological trends of tinea corporis et cruris seen throughout the country were reflected in this study, highlighting the evolving clinical patterns in the epidemic-like scenario in India.