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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]

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. [ABSTRACT FROM AUTHOR]

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. [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]

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.