Search Results
Azole Resistance in Dermatophytes
Prevalence and Mechanism of Action
Azole antifungal agents (eg, fluconazole and itraconazole) have been widely used to treat superficial fungal infections caused by dermatophytes and, unlike the allylamines (such as terbinafine and naftifine), have been associated with resistance development. Although many published manuscripts describe resistance to azoles among yeast and molds, reports describing resistance of dermatophytes are starting to appear. In this review, I discuss the mode of action of azole antifungals and mechanisms underlying their resistance compared with the allylamine class of compounds. Data from published and original studies were compared and summarized, and their clinical implications are discussed. In contrast to the cidal allylamines, static drugs such as azoles permit the occurrence of mutations in enzymes involved in ergosterol biosynthesis, and the ergosterol precursors accumulating as a consequence of azole action are not toxic. Azole antifungals, unlike allylamines, potentiate resistance development in dermatophytes.
Confirmation of Dermatophytes in Nail Specimens Using In-Office Dermatophyte Test Medium Cultures
Insights from a Multispecialty Survey
Using data from a multicenter nationwide multispecialty survey, the authors investigated the efficacy of in-office dermatophyte test medium (DTM) and central laboratory cultures used to confirm onychomycosis across samples collected by podiatric, dermatologic, and primary-care physicians. The samples collected by podiatric physicians were both positive or both negative in 43% and 27% of patients, respectively. Samples harvested by dermatologists were both positive in 37% of patients and both negative in 32%, while the samples collected by primary-care physicians were both positive in 28% of patients and both negative in 38%. The accuracy of DTM and central laboratory tests is dependent on the proper collection of nail samples, and the accuracy of mycologic test results varied significantly across nail specimens harvested by podiatric, dermatologic, and primary-care physicians. DTM culture was found to be an effective and convenient method of confirming dermatophyte infections in patients with signs of onychomycosis. The data presented here indicate that the special expertise of podiatric physicians in treating foot-related illnesses translates into more accurate mycologic testing. (J Am Podiatr Med Assoc 93(3): 195-202, 2003)
Background: Onychomycosis is a chronic fungal nail infection caused predominantly by dermatophytes, and less commonly by nondermatophyte molds and Candida species. Onychomycosis treatment includes oral and topical antifungals, the efficacy of which is evaluated through randomized, double-blind, controlled trials for US Food and Drug Administration approval. The primary efficacy measure is complete cure (complete mycologic and clinical cure). The secondary measures are clinical cure (usually ≤10% involvement of target nail) and mycologic cure (negative microscopy and culture). Some lasers are US Food and Drug Administration approved for the mild temporary increase in clear nail; however, some practitioners attempt to use lasers to treat and cure onychomycosis.
Methods: A systematic review of the literature was performed in July of 2020 to evaluate the efficacy rates demonstrated by randomized controlled trials of laser monotherapy for dermatophyte onychomycosis of the great toenail.
Results: Randomized controlled trials assessing the efficacy of laser monotherapy for dermatophyte toenail onychomycosis are limited. Many studies measured cure rates by means of nails instead of patients, and performed only microscopy or culture, not both. Only one included study reported mycologic cure rate in patients as negative light microscopy and culture (0%). The combined clinical cure rates in short- and long-pulsed laser studies were 13.0%–16.7% and 25.9%, respectively. There was no study that reported the complete cure rate; however, one did report treatment success (mycologic cure [negative microscopy and culture] and ≤10% clinical involvement) in nails as 16.7%.
Conclusions: The effectiveness of lasers as a therapeutic intervention for dermatophyte toenail onychomycosis is limited based on complete, mycologic, and clinical cure rates. However, it may be possible to use different treatment parameters or lasers with a different wavelength to increase the efficacy. Lasers could be a potential management option for older patients and onychomycosis patients with coexisting conditions such as diabetes, liver, and/or kidney diseases for whom systemic antifungal agents are contraindicated or have failed.
Treatment of Dermatophyte Toenail Onychomycosis in the United States
A Pharmacoeconomic Analysis
This study attempted to determine the cost-effectiveness of therapies for dermatophyte toenail onychomycosis in the United States in 2001. The antimycotic agents evaluated were ciclopirox 8% nail lacquer and the oral agents terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A treatment algorithm for the management of onychomycosis was developed, and a meta-analysis was carried out to determine the average mycologic and clinical response rates for the various agents. The cost of the regimen was figured as the sum of the costs of drug acquisition, medical management, and management of adverse effects. The expected cost of management and disease-free days were determined, and a sensitivity analysis was conducted. It was concluded that ciclopirox 8% nail lacquer, which has recently become available in the larger size of 6.6 mL, is a cost-effective agent for the management of toenail onychomycosis. (J Am Podiatr Med Assoc 92(5): 272-286, 2002)
Background
Podiatric physicians routinely use electric drills for the treatment of nail and skin conditions. The grinding process produces human nail and skin dust that is generally vacuumed into bags in the grinding unit. Many of the nails are thought to be mycotic, particularly because they are obtained from patients with symptoms of dermatophyte infections. Currently, there is limited information available on the detection of fungi from nail dust samples. Herein, we attempt to address this situation and outline some of the difficulties that pathology laboratories face in isolating and identifying dermatophytes from nail samples.
Methods
Fifty nail dust bags from podiatric medical clinics across all of the states and territories of Australia were collected and analyzed. Samples from the bags were inoculated onto primary isolation media. Fungal colonies that grew were then inoculated onto potato dextrose agar for identification using standard morphological (macroscopic and microscopic) features.
Results
One hundred fifty-one colonies of dermatophytes were identified from 43 of the 50 samples. In addition 471 nondermatophyte molds were isolated, along with some yeasts and bacteria.
Conclusions
The most common dermatophytes isolated were from the Trichophyton mentagrophytes/interdigitale complexes. Trichophyton rubrum, Trichophyton tonsurans, Trichophyton soudanense, and Epidermophyton floccosum were also isolated. An unidentified group of dermatophytes was also present. The three most common genera of nondermatophyte molds were Aspergillus, Penicillium, and Scopulariopsis, all of which have been implicated in onychomycosis and more general disease. The presence of viable fungal pathogens in the dust could potentially pose a health problem to podiatric physicians.
Traditional methods of diagnosing onychomycosis, such as microscopy, histologic staining, and cultures, may not provide the clinician with documentation before initiating antifungal drug therapy. DNA technology now supplies the tools for increased sensitivity, speed, and accuracy in the diagnostic arena by allowing for the amplification, qualification, and quantitation of DNA. These techniques, already being used to identify many infectious agents, may soon be commonly applied to onychomycosis. This report reviews some of the DNA-based techniques that are currently being used to identify dermatophytes and their possible diagnostic use. (J Am Podiatr Med Assoc 97(2): 134–144, 2007)
Background
Reports of mixed infections with nondermatophyte molds (NDMs) and dermatophytes in onychomycosis are rare, possibly owing to the inhibition of NDM growth during traditional culture. We sought to determine the prevalence of mixed infections in onychomycosis using molecular identification.
Methods
Molecular analyses were used to identify infecting organisms directly from at least two serial great toenail samples from each of the 44 patients.
Results
Mixed infections were present in 41% of the patients (18 of 44). A single coinfecting NDM was the most common mixed infection and was detected in 34% of patients with onychomycosis (15 of 44), with Fusarium oxysporum present in 14% (6 of 44), Scopulariopsis brevicaulis in 9% (4 of 44), Acremonium spp in 2% (1 of 44), Aspergillus spp in 4.5% (2 of 44), and Scytalidium spp in 4.5% (2 of 44). Mixed infections with two NDMs were found in 7% of patients (3 of 44).
Conclusions
Mixed onychomycosis infections may be more prevalent than previously reported.
Background
Dermatomycoses are a group of pathologic abnormalities frequently seen in clinical practice, and their prevalence has increased in recent decades. Diagnostic confirmation of mycotic infection in nails is essential because there are several pathologic conditions with similar clinical manifestations. The classical method for confirming the presence of fungus in nail is microbiological culture and the identification of morphological structures by microscopy.
Methods
We devised a nested polymerase chain reaction (PCR) that amplifies specific DNA sequences of dermatophyte fungus that is notably faster than the 3 to 4 weeks that the traditional procedure takes. We compared this new technique and the conventional plate culture method in 225 nail samples. The results were subjected to statistical analysis.
Results
We found concordance in 78.2% of the samples analyzed by the two methods and increased sensitivity when simultaneously using the two methods to analyze clinical samples. Now we can confirm the presence of dermatophyte fungus in most of the positive samples in just 24 hours, and we have to wait for the result of culture only in negative PCR cases.
Conclusions
Although this PCR cannot, at present, substitute for the traditional culture method in the detection of dermatophyte infection of the nails, it can be used as a complementary technique because its main advantage lies in the significant reduction of time used for diagnosis, in addition to higher sensitivity.
Background: Onychomycosis is a chronic fungal nail infection caused predominantly by dermatophytes, and less commonly by non-dermatophyte molds (NDMs) and Candida species. Onychomycosis treatment includes oral and topical antifungals, the efficacy of which is evaluated through randomized, double-blinded, controlled trials (RCTs) for USA FDA approval. The primary efficacy measure is complete cure (complete mycological and clinical cure). The secondary measures are clinical cure (usually {less than or equal to}10 % involvement of target nail) and mycological cure (negative microscopy and culture). Some lasers are FDA-approved for the mild temporary increase in clear nail; however, some practitioners attempt to use lasers to treat and cure onychomycosis. Methods: A systematic review of the literature was performed in July 2020 to evaluate the efficacy rates demonstrated by RCTs of laser monotherapy for dermatophyte onychomycosis of the great toenail. Results: RCTs assessing the efficacy of laser monotherapy for dermatophyte toenail onychomycosis are limited. Many studies measured cure rates via nails instead of patients, and performed only microscopy or culture, not both. Only one included study reported mycological cure rate in patients as negative light microscopy and culture (0%). The combined clinical cure rates in short- and long-pulsed laser studies were (13.0-16.7% and 25.9%, respectively). There was no study that reported the complete cure rate, however, one did report treatment success (mycological cure (negative microscopy and culture) and {less than or equal to}10% clinical involvement) in nails as 16.7%. Conclusions: The effectiveness of lasers as a therapeutic intervention for dermatophyte toenail onychomycosis is limited based on complete, mycological, and clinical cure rates. However, it may be possible to use different treatment parameters or lasers with a different wavelength to increase the efficacy. Lasers could be a potential management option for older patients and onychomycosis patients with coexisting conditions such as diabetes, liver and/or kidney diseases for whom systemic antifungal agents are contraindicated or have failed.
Onychomycosis is the most frequently encountered condition in podiatric practice in the United States. A variety of modalities are available to confirm the presumptive diagnosis of onychomycosis. This study was conducted to compare the results of in-office dermatophyte test medium cultures with those of mycology laboratory analysis for 100 cases of suspected onychomycosis in a geriatric population. The results demonstrated that 20% of the patients had dermatophyte involvement, 56% had saprophyte involvement, and 19% had yeast involvement. Only 50% of positive dermatophyte test medium cultures correlated with a positive microscopic fungal culture for dermatophytes. Given these results, it is questionable whether in-office dermatophyte test medium cultures should be routinely used in geriatric patients for the diagnosis of onychomycosis. The authors believe mycology laboratory testing with fluorescent potassium hydroxide preparations and microscopic fungal cultures to be superior to in-office dermatophyte test medium cultures for the diagnosis of onychomycosis in geriatric patients.
