Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human populations. Here, we reviewed published reports (2009–2024) of dermatophyte infections in animals and in humans with a history of animal contact. A literature search was completed in October 2024 using PubMed, Embase (Ovid), and Web of Science (Core Collection), which identified 250 articles. Generally, dermatophytes tend to infect younger animals with long hair and exhibit a species-specific host range. Microsporum canis was the most commonly reported species—linked to cats—that can cause tinea capitis, especially concerning the development of kerion in children. Trichophyton verrucosum is strongly associated with cattle. The Trichophyton mentagrophytes complex shows a diverse range of animal hosts, with rabbits being most frequently reported; however, T. mentagrophytes var. erinacei is almost exclusively isolated from hedgehogs, and T. mentagrophytes var. benhamiae is more commonly found on rodents (e.g., guinea pigs). Lastly, the geophilic Nannizia gypsea has been isolated from both dogs and cats. Managing dermatophyte zoonoses is an ongoing challenge, as healthcare providers may empirically treat with corticosteroids or antibacterial agents due to its atypical inflammatory appearance. Evidence of in vitro resistance against griseofulvin and fluconazole has been documented in multiple zoonotic dermatophyte species. Resistance development against terbinafine and itraconazole is also a possibility, although the number of reports is scarce. Under the principles of the One Health approach, research on human fungal diseases should take animal and environmental factors into account. A renewed call for increased testing efforts is warranted.

The emergence of antifungal resistance calls for continued research efforts to better guide healthcare providers in treatment selection and outcomes. Unlike bacterial infections, treatment of superficial fungal infections is mainly limited to allylamines (terbinafine) and azoles (itraconazole). Here, we aim to update our current understanding of resistance mechanisms against allylamine and azole antifungals in the Trichophyton genus. Resistance development has been demonstrated in vitro by challenging Trichophyton isolates with allylamines or azoles at levels below the minimum inhibitory concentration (MIC), which corroborates the observation of clinical resistance. Frequently reported mechanisms of resistance include: (I) Alterations of the drug target by single-nucleotide variations (SNVs) of the SQLE/ERG1 and ERG11 genes; in particular, SQLE SNVs (Leu393Phe, Leu393Ser, and Phe397Leu) have been frequently reported in isolates with high terbinafine MICs; (II) overexpression of the target enzyme for azoles (ERG11) and downstream genes in the ergosterol biosynthesis pathway can decrease the effective drug concentration as well as prevent the depletion of ergosterol and the accumulation of toxic sterol intermediates; (III) the up-regulation of drug efflux channels—belonging to the ABC superfamily (PDR1, MDR2, MDR3, MDR4), MFS superfamily (MFS1), or Pma1 (plasma membrane ATPase 1)—can reduce the effective concentrations of terbinafine and azoles. The possibility of multidrug resistance has been shown in Trichophyton strains, of both human and animal origins, harboring multiple resistance mechanisms (e.g., target alteration/overexpression and drug efflux channels). Tackling the issue of antifungal resistance will require an integrated approach with multidisciplinary efforts including surveillance initiatives and antifungal stewardship programs. However, these efforts are hampered by the current limited accessibility of antifungal susceptibility testing as well as the limited choice of antifungals available in routine practice. A better understanding of resistance mechanisms could help develop targeted, molecular-based assays.

Onychomycosis is an under-recognized healthcare burden. Despite the risk of misdiagnosis, confirmatory laboratory testing is under-utilized. Histopathologic examination with polymerase chain reaction (PCR) is currently the most effective diagnostic method; it offers direct detection and identification of a fungal invasion. In this retrospective cohort study, we assessed confirmatory testing results, with matching clinical diagnoses, in 96,293 nail specimens submitted during a 9-month period from 2022 to 2023. Toenail specimens were examined using fungal culture, histopathology and/or PCR. Clinical diagnoses were identified using the International Classification of Diseases 10th Revision codes. For clinically diagnosed onychomycosis patients, the overall positivity rate was 59.4%; a similar positivity rate (59.5%) was found in patients with clinically diagnosed non-fungal nail dystrophy. Performing a histopathologic examination with PCR was more likely to provide pathogen identification results than using fungal culture. Male patients had a higher rate of onychomycosis overall; however, female patients had more non-dermatophyte mold onychomycosis caused by Aspergillus. Clinically diagnosed onychomycosis patients with a co-diagnosis of tinea pedis were more likely to test positive for onychomycosis by PCR (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 2.7–6.4), histopathology (OR: 2.5; 95% CI: 2.0–3.1) and fungal culture (OR: 3.2; 95% CI: 1.5–6.6). Our results support the use of confirmatory laboratory testing when there is a clinical diagnosis of onychomycosis.

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.

Onychomycosis is a common nail infection. Terbinafine-resistant dermatophyte infections pose an emerging global public health concern, but few cases have been described in the United States. We retrospectively reviewed and characterized clinical, histopathological, and mycological features of patients with mycologically confirmed onychomycosis who failed oral terbinafine treatment for onychomycosis at a U.S. academic nail referral center and ascertained for terbinafine-resistant isolates. During 1 June 2022–31 January 2023 at Weill Cornell Medicine in New York City, USA, 96 patients with mycologically confirmed onychomycosis were treated with oral terbinafine. Among 64 patients with adequate follow-up, 36 had clinical or complete cure. Of 28 patients who failed treatment, 17 underwent terbinafine resistance testing. Trichophyton rubrum with terbinafine resistance-conferring mutations was isolated from two patients. Overall, terbinafine failures for onychomycosis were relatively common, with some cases associated with terbinafine-resistant T. rubrum infections. These findings underscore the need for a clinical awareness of this emerging problem and public health efforts to monitor and prevent spread. We highlight the importance of diagnostic testing and species identification for onychomycosis patients and the increasingly important role of fungal identification and susceptibility testing to guide therapy.