[Lomentospora prolificans Fungemia in a Patient With T-Cell Large Granular Leukemia: A Rare Pathogen in Türkiye]. / T-hücreli Büyük Granüler Lösemili Bir Hastada Lomentospora prolificans Fungemisi: Türkiye'de Nadir Bir Etken.

Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally, Lomentospora prolificans, which mainly affects immunosuppressed individuals, is rarely encountered and is more prevalent in arid climates, particularly in Australia and Spain. L.prolificans is a fungus commonly found in environmental sources such as contaminated water and soil. This species is known as an opportunistic pathogen that can cause deep-seated fungal infections, especially in immunosuppressed individuals. In this case report, a fatal case of L.prolificans fungemia in a patient with T-cell large granular leukemia during profound neutropenia was presented. The patient admitted to the hospital with prolonged fever, neutropenia, and shortness of breath. Antibiotherapy was administered to the patient for febrile neutropenia, but the fever persisted and his clinical status rapidly deteriorated. L.prolificans was isolated from the blood culture, and considering its antifungal resistance, combination therapy of voriconazole and terbinafine was initiated. However, the patient died of septic shock and multiple organ failure. In conclusion, although L.prolificans infections are rare, they can be life-threatening, especially in immunosuppressed individuals. Diagnosis and treatment of such infections may be difficult, therefore rapid diagnostic methods and appropriate treatment protocols should be developed. Consideration of infections caused by rare fungal pathogens in patients with risk factors may be critical for patient care. The literature review revealed that the first case of L.prolificans fungemia from Türkiye was reported in 2023. This case presentation represents the second reported case. However, in our case, L.prolificans fungemia occurred in 2018, it can be considered that L.prolificans may have been an invasive fungal pathogen of significant concern in Türkiye much earlier than previously documented.

Pathogenic Aspergillus Strains Identification and Antifungal Susceptibility Analysis of 452 Cases with Otomycosis in Jingzhou, China.

OBJECTIVE: To study the distribution of pathogenic Aspergillus strains of otomycosis in central China and the identification of their antifungal sensitivity. METHODS: We collected external ear canal secretions clinically diagnosed as otomycosis from April 2020 to January 2023 from the Department of Otolaryngology-Head and Neck Surgery in central China. The pathogenic Aspergillus strains were identified through morphological examination and sequencing. The antifungal sensitivity was performed using the broth microdilution method described in the Clinical Laboratory Standard Institute document M38-A3. RESULTS: In the 452 clinical strains isolated from the external ear canal, 284 were identified as Aspergillus terreus (62.83%), 92 as Aspergillus flavus (20.35%), 55 as Aspergillus niger (12.17%). In antifungal susceptibility tests the MIC of Aspergillus strains to bifonazole and clotrimazole was high,all the MIC90 is > 16 ug/mL. However, most Aspergillus isolates show moderate greatly against terbinafine, itraconazole and voriconazole. CONCLUSION: A. terreus is the most common pathogenic Aspergillus strain in otomycosis in central China. The selected topical antifungal drugs were bifonazole and clotrimazole; the drug resistance rate was approximately 30%. If the infection is persistent and requires systemic treatment, terbinafine and itraconazole can be used. The resistance of Aspergillus in otomycosis to voriconazole should be screened to avoid the systemic spread of infection in immunocompromised people and poor compliance with treatment. However, the pan-azole-resistant strain of Aspergillus should be monitored, particularly in high-risk patients with otomycosis.

In vitro antifungal susceptibility of the dermatophytes: a single center study from Eastern Black Sea Region of Turkey.

OBJECTIVE: A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs. PATIENTS AND METHODS: Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine. RESULTS: A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum (13.8% in 49 samples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance. CONCLUSIONS: The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development.

Low toxicity contributes to Sporothrix globosa invade the skin of patients in low-epidemic areas of China.

OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.

The Ptk2-Pma1 pathway enhances tolerance to terbinafine in Trichophyton rubrum.

The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae. Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.

Resistance Profile, Terbinafine Resistance Screening and MALDI-TOF MS Identification of the Emerging Pathogen Trichophyton indotineae.

The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains.

Zoonotic Majocchi's Granuloma of the Vulva.

A healthy 32-year-old woman presented to clinic with tender pruritic lesions of 2-month duration at the vulva and lesions for weeks on the shins. She was treated with topical corticosteroids and intravenous vancomycin without significant improvement. On examination, dozens of follicular hemorrhagic papulopustules were detected at the suprapubic area and vulva (Figure 1). Similar but less prominent lesions were observed on the shins as well. Biopsies of the vulva and shin revealed a follicular inflammatory infiltrate of neutrophils, histiocytes, and lymphocytes as well as fungal hyphae within the follicular infundibulum and hair shafts, consistent with Majocchi's granuloma (MG). Gram and Fite-Faraco staining, direct immunofluorescence, and bacterial culture were negative. Tissue culture grew Trichophyton mentagrophytes, which was identified using sequence analysis of the D1/D2 region of the 28s rDNA. Minimum inhibitory concentrations for terbinafine, ketoconazole, and itraconazole were determined, with terbinafine having the lowest concentration. Additional history revealed that shortly prior to commencement of her clinical manifestations, the patient had acquired a pet guinea pig with eruptions and hair loss (Figure 2). The patient was prescribed ketoconazole cream and terbinafine, 250 mg daily, with almost immediate improvement. Based on clinical response, the patient remained on terbinafine and ketoconazole cream for 6 months. Her skin remained clear 4 months after discontinuing all antifungals. Based on the results of patient's culture, a veterinarian treated her guinea pig successfully with systemic terbinafine and miconazole lotion.

Nodular lesions of the buttock for 20 years: the challenge of chromoblastomycosis in non-endemic settings.

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.

Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

In vitro determination of the combination of ciclopirox and terbinafine in the treatment of dermatophytosis.

INTRODUCTION: The cases of dermatophytosis are increasing and they are associated with a higher number of therapeutic failures leading the doctor to prescribe combinations of antifungals as therapy. The objective was to evaluate the interaction of terbinafine and ciclopirox, the most commonly antifungals used in the clinic, in dermatophyte isolates. METHODOLOGY: The minimum inhibitory concentrations (MIC) of ciclopirox and terbinafine were determined by the broth microdilution method according CLSI and the checkerboard assay was used to evaluate the interaction between the antifungal agents. RESULTS: For terbinafine the mic50 was 0.125 ug/mL and mic90 was 0.250 ug/mL. For ciclopirox the values were 2.0 ug/mL for mic50 and 4.0 ug/mL for mic90. No synergistic interaction was observed for the dermatophyte isolates tested. CONCLUSION: These results suggest that the use of terbinafine in combination with ciclopirox, which is widely used in the clinic, may not be a good choice for the treatment of onychomycosis.

Whole genome characterization of Trichophyton indotineae isolated in Singapore.

Complete genome sequences from two Trichophyton indotineae isolates were obtained from a 23-year-old male presenting with tinea cruris after an overseas recreational water exposure and from a 53-year-old female patient with unknown travel history. Analysis of the squalene epoxidase gene and the cyp51 gene family showed an absence of mutations, correlating with phenotypic drug susceptibility. The Single Nucleotide Polymorphisms (SNPs) distance between both isolates was 92. Within the T. indotineae cluster, SNPs ranged from 7 to 182, suggesting a high genetic relatedness with other South Asian isolates. This study suggests that the prevalence of T. indotineae is under-reported and more widespread than previously thought.

Trichophyton indotineae, is a fungus causing difficult to treat ringworm infections. Two isolates were sequenced and their relationship and to other isolates was characterized. We also studied the genes responsible for first-line antifungal treatment.

Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes.

Trichophyton mentagrophytes is a zoophilic dermatophyte that can cause dermatophytosis in humans and animals. Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of T. mentagrophytes. Our findings suggest that cationic antimicrobial peptide (ACP5) not only possesses stronger activity against T. mentagrophytes than fluconazole, but also shows lower toxicity to L929 mouse fibroblast cells than terbinafine. Notably, its resistance development rate after resistance induction was lower than terbinafine. The present study aimed to evaluate the fungicidal mechanism of ACP5 in vitro and its potential to treat dermatophyte infections in vivo. ACP5 at 1 ×MIC completely inhibited T. mentagrophytes spore germination in vitro. ACP5 severely disrupts the mycelial morphology, leading to mycelial rupture. Mechanistically, ACP5 induces excessive ROS production, damaging the integrity of the cell membrane and decreasing the mitochondrial membrane potential, causing irreversible damage in T. mentagrophytes. Furthermore, 1% ACP5 showed similar efficacy to the commercially available drug 1% terbinafine in a guinea pig dermatophytosis model, and the complete eradication of T. mentagrophytes from the skin by ACP5 was verified by tissue section observation. These results indicate that ACP5 is a promising candidate for the development of new agent to combat dermatophyte resistance.

Widespread dermatophytosis in a healthy adolescent: the first report of multidrug-resistant Trichophyton indotineae infection in the UAE.

A multidrug-resistant dermatophyte species recently arose in India, first described as terbinafine-resistant Trichophyton interdigitale and soon given a separate name: T. indotineae. Thanks to its treatment recalcitrance, person-to-person spread, and frequent travel, before long it was identified in many countries on all continents. We describe here the case of a boy with widespread, extremely pruritic, inflammatory dermatophytosis affecting his face, neck, trunk, and extremities, unsuccessfully treated for months with oral terbinafine and fluconazole and a range of topical antimycotics. Qualitative polymerase chain reaction of skin scrapings from his lesions identified a T. interdigitale complex fungus, highly probably T. indotineae due to conspecificity and antifungal resistance. Oral itraconazole, administered over 8 weeks, cleared the infection. Because the patient had not traveled outside the United Arab Emirates for months before the infection became obvious, it must have been acquired from a local source.

Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: A prospective multicentric study.

BACKGROUND: Terbinafine, an allylamine antifungal, is crucial for treating dermatophytosis by inhibiting squalene epoxidase (SQLE) in the ergosterol biosynthetic pathway. However, resistance is emerging, particularly in India and Southeast Asia, but reports of resistance spread worldwide. Despite this, comprehensive studies on terbinafine resistance in Trichophyton are still limited. OBJECTIVES: This research aimed to determine the prevalence of terbinafine resistance in the Czech Republic, with a focus on Trichophyton rubrum and Trichophyton mentagrophytes, and investigate the underlying molecular mechanisms. PATIENTS/METHODS: A total of 514 clinical strains of T. rubrum and 240 T. mentagrophytes collected from four Czech clinical institutions were screened for terbinafine resistance. Molecular investigations included DNA sequencing, specifically the ITS rDNA region and SQLE gene, as well as antifungal susceptibility testing following EUCAST guidelines. RESULTS: While no resistance was observed in T. rubrum, 2.5% of T. mentagrophytes strains exhibited resistance, marked by the F397L mutation in SQLE. Notably, resistance surged from 1.2% in 2019 to 9.3% in 2020 but reverted to 0% in 2021. All resistant strains were identified as T. mentagrophytes var. indotineae. Resistant strains exhibited high MICs for terbinafine (≥4 mg L-1 ) but low MICs to the other seven antifungals tested except for fluconazole. CONCLUSIONS: This study highlights the emergence of terbinafine-resistant T. mentagrophytes strains in the Czech Republic, with the F397L mutation being pivotal. Due to the relatively low resistance level, the current guidelines for dermatomycosis treatment in the Czech Republic remain effective, but ongoing surveillance is essential for timely adaptations if resistance patterns change.

Activity of amorolfine or ciclopirox in combination with terbinafine against pathogenic fungi in onychomycosis-Results of an in vitro investigation.

BACKGROUND: Onychomycoses are difficult-to-treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. OBJECTIVES: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. METHODS: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96-well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. RESULTS: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. CONCLUSIONS: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non-dermatophyte fungus such as S. brevicaulis.

Molecular Verification of Trichophyton in the Brazilian URM Culture Collection.

Trichophyton species cause dermatophytosis in humans, with a high, worldwide frequency of reports and important public health relevance. We evaluated 61 Trichophyton strains from different sources deposited in the University Recife Mycology (URM) culture collection of the Universidade Federal de Pernambuco, Brazil. Strains were phenotypically identified and confirmed by sequencing Internal Transcribed Spacers rDNA and partial beta-tubulin 2-exon. Additionally, we evaluated their susceptibility to terbinafine and itraconazole. Physiological analyses included urease activity and growth in casein medium. Phenotypic methods allowed the reliable identification of T. rubrum only, whereas, for other species, molecular methods were mandatory. All Trichophyton species exhibited susceptibility profiles to itraconazole (0.04-5.33 µg/mL) and terbinafine (0.17-3.33 µg/mL). Our analyses revealed a heterogeneous distribution of T. mentagrophytes, which does not support the current distribution within the species complex of T. mentagrophytes and its genotypes.

Invasive fungal infections and oomycoses in cats 2. Antifungal therapy.

CLINICAL RELEVANCE: Invasive fungal infections (IFIs) and oomycoses (hereafter termed invasive fungal-like infections [IFLIs]) are characterised by penetration of tissues by fungal elements. The environment is the most common reservoir of infection. IFIs and IFLIs can be frustrating to treat because long treatment times are usually required and, even after attaining clinical cure, there may be a risk of relapse. Owner compliance with medication administration and recheck examinations can also decline over time. In addition, some antifungal drugs are expensive, have variable interpatient pharmacokinetic properties, can only be administered parenterally and/or have common adverse effects (AEs). Despite these limitations, treatment can be very rewarding, especially when an otherwise progressive and fatal disease is cured. AIM: In the second of a two-part article series, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties, and AEs of antifungal drugs are reviewed, and the treatment and prognosis of specific IFIs/IFLIs - dermatophytic pseudomycetoma, cryptococcosis, sino-orbital aspergillosis, coccidioidomycosis, histoplasmosis, sporotrichosis, phaeohyphomycosis, mucormycosis and oomycosis - are discussed. Part 1 reviewed the diagnostic approach to IFIs and IFLIs. EVIDENCE BASE: Information on antifungal drugs is drawn from pharmacokinetic studies in cats. Where such studies have not been performed, data from 'preclinical' animals (non-human studies) and human studies are reviewed. The review also draws on the wider published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology. ABBREVIATIONS FOR ANTIFUNGAL DRUGS: AMB (amphotericin B); FC (flucytosine); FCZ (fluconazole); ISA (isavuconazole); ITZ (itraconazole); KCZ (ketoconazole); PCZ (posaconazole); TRB (terbinafine); VCZ (voriconazole).

CONTROLLED CLINICAL TRIAL USING TERBINAFINE NEBULIZATION TO TREAT WILD LAKE ERIE WATERSNAKES (NERODIA SIPEDON INSULARUM) WITH OPHIDIOMYCOSIS.

Ophidiomycosis (snake fungal disease) is an important infectious disease caused by the fungus Ophidiomyces ophidiicola. To mitigate the disease's impact on individual snakes, a controlled clinical trial was conducted using terbinafine nebulization to treat snakes with ophidiomycosis. Fifty-three wild-caught Lake Erie watersnakes (Nerodia sipedon insularum) with apparent ophidiomycosis (skin lesions present, qPCR positive for O. ophidiicola) were divided into treatment and control groups: treatment snakes were nebulized with a 2 mg/ml terbinafine solution for 30 min daily for 30 d; control snakes received nebulization with 0.9% saline or no nebulization. Weekly physical exams were conducted to assign disease severity scores based on the number, type, location, and size of lesions, and qPCR was repeated after each 30-d course of treatment. Persistently qPCR-positive snakes received multiple nebulization courses. Terbinafine nebulization showed mixed results as a treatment for ophidiomycosis: 29.2% of animals treated with terbinafine showed molecular resolution of external disease, based on antemortem swabbing, following 3-6 mon of daily nebulization; this was significantly more than with saline nebulization (5%), but molecular resolution also occurred in 11.1% of snakes that received no treatment. Terbinafine nebulization did not significantly decrease clinical disease, as measured by disease severity scores. Evaluating molecular response to treatment using fungal quantities, terbinafine nebulization significantly reduced fungal quantity after three or more courses of treatment. These results indicate that, although terbinafine nebulization is a promising treatment for ophidiomycosis, snakes may require multiple nebulization courses and disease may not always resolve completely, despite treatment. This treatment may be most useful in snakes from managed populations that can be treated for several months, rather than wild snakes who are not releasable after multiple months in captivity.

Treatment of onychomycosis in an era of antifungal resistance: Role for antifungal stewardship and topical antifungal agents.

A growing body of literature has marked the emergence and spread of antifungal resistance among species of Trichophyton, the most prevalent cause of toenail and fingernail onychomycosis in the United States and Europe. We review published data on rates of oral antifungal resistance among Trichophyton species; causes of antifungal resistance and methods to counteract it; and in vitro data on the role of topical antifungals in the treatment of onychomycosis. Antifungal resistance among species of Trichophyton against terbinafine and itraconazole-the two most common oral treatments for onychomycosis and other superficial fungal infections caused by dermatophytes-has been detected around the globe. Fungal adaptations, patient characteristics (e.g., immunocompromised status; drug-drug interactions), and empirical diagnostic and treatment patterns may contribute to reduced antifungal efficacy and the development of antifungal resistance. Antifungal stewardship efforts aim to ensure proper antifungal use to limit antifungal resistance and improve clinical outcomes. In the treatment of onychomycosis, critical aspects of antifungal stewardship include proper identification of the fungal infection prior to initiation of treatment and improvements in physician and patient education. Topical ciclopirox, efinaconazole and tavaborole, delivered either alone or in combination with oral antifungals, have demonstrated efficacy in vitro against susceptible and/or resistant isolates of Trichophyton species, with low potential for development of antifungal resistance. Additional real-world long-term data are needed to monitor global rates of antifungal resistance and assess the efficacy of oral and topical antifungals, alone or in combination, in counteracting antifungal resistance in the treatment of onychomycosis.