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Introduction: There is an increasing number of reports of Trichophyton indotineae infections. This species is usually poorly responsive to terbinafine. Areas covered: A literature search was conducted in May 2024. T.indotineae infections detected outside the Indian subcontinent are generally associated with international travel. Reports of local spread are mounting. As a newly identified dermatophyte species closely related to the T. mentagrophytes complex with limited genetic and phenotypic differences, there is an unmet need to develop molecular diagnosis for T. indotineae. Terbinafine has become less effective as a first-line agent attributed to mutations in the squalene epoxidase gene (Leu393Phe, Phe397Leu). Alternative therapies include itraconazole for a longer time-period or a higher dose (200 mg/day or higher). Generally, fluconazole and griseofulvin are not effective. In some cases, especially when the area of involvement is relatively small, topical non-allylamine antifungals may be an option either as monotherapy or in combination with oral therapy. In instances when the patient relapses after apparent clinical cure then itraconazole may be considered. Good antifungal stewardship should be considered at all times. Expert Opinion: When both terbinafine and itraconazole are ineffective, options include off-label triazoles (voriconazole and posaconazole). We present four patients responding to these newer triazoles. Plain Language Summary: Ringworm (dermatophytosis, tinea) is a fungal infection of the skin, hair and nails that is commonly seen by primary and secondary healthcare providers. An estimated 20–25% of the global population is affected by this condition. In Europe and the United States, tineas are often treated empirically using over-the-counter medications, which can increase the risk of resistance development. While antifungal resistance is not a new problem, this topic has garnered the attention of physicians and researchers in recent years due to an outbreak from South Asia caused by a new pathogen known as Trichophyton indotineae. In this review, we summarize the global prevalence, diagnosis methods, antifungal resistance profile and treatment options for T. indotineae. Currently, most cases outside of South Asia are linked to international travel, there is evidence suggesting local person-to-person transmission and transmission via animal contact. One hurdle to surveilling the spread of this pathogen is the requirement of complex molecular diagnosis, tackling this challenge will require the development of newer assays. Terbinafine, a widely available antifungal drug, is becoming less effective owing to resistance mutations of the squalene epoxidase gene. Itraconazole has shown effectiveness, especially with a higher dose and a longer treatment duration. There is a significant risk of T. indotineae infections becoming chronic with episodes of relapse. When both terbinafine and itraconazole fail, newer agents such as posaconazole and voriconazole can be considered. Combination therapy using oral and topical medications should also be considered. [ABSTRACT FROM AUTHOR]

Onychomycosis is a recalcitrant fungal infection of the nail unit that can lead to secondary infections and foot complications. Accurate pathogen identification by confirmatory testing is recommended to improve treatment outcomes. In this study, we reviewed the records of 710,541 patients whose nail specimens were sent to a single molecular diagnostic laboratory between 2015 and 2024. PCR testing revealed a more comprehensive spectrum of pathogens than previously reported, which was corroborated by the demonstration of fungal invasion on histopathology. Consistent with our current understanding, the T. rubrum complex (54.3%) are among the most common pathogens; however, a significant portion of mycology-confirmed diagnoses were caused by the T. mentagrophytes complex (6.5%), Aspergillus (7.0%) and Fusarium (4.5%). Females were significantly more likely to be infected with non-dermatophytes molds (NDMs; OR: 2.0), including Aspergillus (OR: 3.3) and Fusarium (OR: 2.0), and yeasts (OR: 1.5), including Candida albicans (OR: 2.0) and C. parapsilosis (OR 1.6), than males. The T. mentagrophytes complex became more prevalent with age, and conversely the T. rubrum complex became less prevalent with age. Patients aged ≥65 years also demonstrated a higher likelihood of contracting onychomycosis caused by NDMs (OR: 1.6), including Aspergillus (OR: 2.2), Acremonium (OR: 3.5), Scopulariopsis (OR: 2.9), Neoscytalidium (OR: 3.8), and yeasts (OR: 1.8), including C. albicans (OR: 1.9) and C. parapsilosis (OR: 1.7), than young adults. NDMs (e.g., Aspergillus and Fusarium) and yeasts were, overall, more likely to cause superficial onychomycosis and less likely to cause dystrophic onychomycosis than dermatophytes. With regards to subungual onychomycosis, Aspergillus, Scopulariopsis and Neoscytalidium had a similar likelihood as dermatophytes. The advent of molecular diagnostics enabling a timely and accurate pathogen identification can better inform healthcare providers of appropriate treatment selections and develop evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Background: There is a concerning rise in antifungal‐resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. Objectives: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. Methods: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18‐month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real‐time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). Results: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. Conclusion: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk. [ABSTRACT FROM AUTHOR]

The three most commonly used methods for diagnosing non-dermatophyte mold (NDM) onychomycosis are culture, polymerase chain reaction (PCR), and histopathology. Toenail samples from 512 patients (1 sample/patient) with suspected onychomycosis were examined using all three diagnostic tests. A statistically significant association was found between PCR and histopathology results, as well as between fungal culture and histopathology results. All PCR-positive and culture-positive dermatophyte samples were confirmed by histopathology. However, 15/116 (12.9%) of culture-positive NDM samples had negative histopathology results, while all PCR-positive NDM samples were confirmed by histopathology. The overall rate of dermatophyte detection was higher using PCR compared to culture (38.9% vs. 11.7%); the lower rate of NDM detection by PCR (11.7% vs. 38.9%) could be attributed to the restriction of the assay design to seven pre-selected targets. When repeat sampling in the clinic is not possible, a combination of NDM detection by PCR and positive histopathology of hyphae may be a proxy for NDM infection, particularly where the NDM occurs without a concomitant dermatophyte. There was a high degree of correlation between negative PCR and negative histopathology. A negative PCR result with negative histopathology findings may be a reliable proxy for the diagnosis of non-fungal dystrophy. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusions Onychomycosis is a common nail disease that is often difficult to treat with a high risk of recurrence.To update our current understanding of the etiologic profile in pediatric patients with onychomycosis utilizing molecular diagnosis by polymerase chain reaction (PCR) combined with histopathologic examination.Records of 19,770 unique pediatric patients were retrieved from a single diagnostic laboratory in the United States spanning over a 9‐year period (March 2015 to April 2024). This cohort represents patients clinically suspected of onychomycosis seen by dermatologists and podiatrists. Dermatophytes, nondermatophyte molds (NDMs), and yeasts were identified by multiplex real‐time PCR corroborated by the demonstration of fungal invasion on histopathology.An average of 37.0% of all patients sampled were mycology‐confirmed to have onychomycosis. Most patients were between ages 11 and 16 years, and the rate of mycologically confirmed onychomycosis was significantly higher among the 6‐ to 8‐year (47.2%) and 9‐ to 11‐year (42.7%) age groups compared to the 0‐ to 5‐year (33.1%), 12‐ to 14‐year (33.2%), and 15‐ to 17‐year (36.7%) age groups. The majority of infections were caused dermatophytes (74.7%) followed by NDMs (17.4%). The Trichophyton rubrum complex represents the dominant pathogen with higher detection rates in the 6‐ to 11‐year‐olds. Fusarium was the most commonly isolated NDM with an increasing prevalence with age.Elementary school‐aged children have a higher risk of contracting onychomycosis which may be attributed to the onset of hyperhidrosis at puberty, use of occlusive footwear, nail unit trauma, and walking barefoot. Fusarium onychomycosis may be more prevalent than expected, and this may merit consideration of management strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives : Cutaneous infections of fungal and bacterial origins are common. An accurate diagnosis-especially concerning pathogens that are difficult to isolate on culture-can be achieved using molecular methods (PCR) with a short turnaround time. Methods : We reviewed records of skin specimens (superficial scrapings) submitted by dermatologists across the United States with a clinically suspected dermatitis. As per physician's order, specimens were tested for infections either fungal (N = 4262) or bacterial (N = 1707) in origin. All unique specimens (one per patient) were subjected to real-time PCR assays where cases suspected of a fungal etiology were tested for dermatophytes, Malassezia and Candida , and cases suspected of a bacterial etiology were tested for Streptococcus pyogenes , Staphylococcus aureus , and the mecA gene potentially conferring β-lactam resistance. Results : Fungal agents were detected in 32.8% (SD: 4.5) of the submitted specimens, with most attributed to dermatophytes (19.3% (SD: 4.9)), followed by Malassezia (8.7% (SD: 2.8)) and Candida (2.9% (SD: 1.0)). Dermatophyte detection was more common in the elderly (≥65 years) compared to young adults (18-44 years) (OR: 1.8 (95% CI: 1.5, 2.2)), whereas Malassezia was more commonly detected in younger age groups (12.1-13.6%) than the elderly (5.6%). Candida was more frequently observed in females while dermatophytes and Malassezia were more frequently observed in males. Approximately one quarter of the submitted skin specimens tested positive for S. aureus (23.6% (SD: 3.4)), of which 34.4% (SD: 9.8) exhibited concurrent detection of the mecA gene. An S. aureus detection was more frequently observed in males (OR: 1.5 (95% CI: 1.2, 1.9)) and in children (OR: 1.7 (95% CI: 1.2, 2.5)). Streptococcus pyogenes was rarely detected. Among specimens positive for dermatophytes, 12.0% (20/166) showed co-detection of S. aureus and mecA , which is in contrast to 6.8% (70/1023) detected in samples without a fungal co-detection and 6.2% (8/130) in samples positive for Malassezia . Conclusions : PCR testing, when available, can be valuable as a part of routine care for diagnosing patients with clinically suspected skin infections. Further studies are warranted to survey the prevalence of resistant S. aureus isolates in dermatology outpatients, in particular with regard to the association with dermatophyte infections.