Placebo cure rates vary among randomized clinical trials for onychomycosis, but the factors influencing these cure rates have not been systematically investigated. The PubMed database and reference sections of relevant publications were searched for randomized controlled trials of dermatophyte toenail onychomycosis that included a placebo control and that assessed cure rates. From 21 studies, the pooled mean ± SD placebo cure rates regarding mycological, clinical, and complete cure were 8.7% ± 3.7%, 3.4% ± 2.2%, and 1.2% ± 1.4%, respectively. There was no statistically significant difference between oral and topical treatments. None of the cure rates significantly correlated with any of the participant or study design characteristics analyzed. Placebo cure rates in randomized controlled trials of toenail onychomycosis are relatively low and are independent of the study characteristics.
Because of the ubiquitous nature of dermatophytes and a lack of an adaptive immune response in the nail plate, recurrence and relapse rates associated with superficial fungal infections are high (10%–53%). Cured or improved dermatophytosis patients could become reinfected if exposed to fungal reservoirs, such as an infected shoe, sock, or textile. To prevent this, footwear, sock, and textile sanitization methods can be used. To provide insight into effective sanitization options, the focus of this article is to review footwear, sock, and textile sanitization studies conducted throughout history (1920–2016). Thirty-three studies are covered in this review, encompassing techniques ranging from formaldehyde fumigation and foot powder application, to more modern approaches such as UV light and silver-light irradiation technologies. Older sanitization methods (eg, boiling, use of chlorine and salts) are quite limited in their practicality, as they can result in health complications and ruin shoe integrity. Newer approaches to shoe and sock sanitization, such as ozone application and UV irradiation, have shown very promising results. Further research is still needed with these modern techniques, as knowledge gaps and cost prevent the creation of standardized parameters for successful use. By combining sanitization methods with other preventative measures, protection against reinfection may be enhanced.
Background: We sought to determine the frequency of toenail onychomycosis in diabetic patients, to identify the causative agents, and to evaluate the epidemiologic risk factors.
Methods: Data regarding patients’ diabetic characteristics were recorded by the attending internal medicine clinician. Clinical examinations of patients’ toenails were performed by a dermatologist, and specimens were collected from the nails to establish the onycomycotic abnormality. All of the specimens were analyzed by direct microscopy and culture.
Results: Of 321 patients with type 2 diabetes mellitus, clinical onychomycosis was diagnosed in 162; 41 of those diagnoses were confirmed mycologically. Of the isolated fungi, 23 were yeasts and 18 were dermatophytes. Significant correlations were found between the frequency of onychomycosis and retinopathy, neuropathy, obesity, family history, and duration of diabetes. However, no correlation was found with sex, age, educational level, occupation, area of residence, levels of hemoglobin A1c and fasting blood glucose, and nephropathy. The most frequently isolated agents from clinical specimens were yeasts.
Conclusions: Long-term control of glycemia to prevent chronic complications and obesity and to promote education about the importance of foot and nail care should be essential components in preventing onychomycosis and its potential complications, such as secondary foot lesions, in patients with diabetes mellitus. (J Am Podiatr Med Assoc 101(1): 49–54, 2011)
Onychomycosis, most commonly caused by two species of dermatophyte fungi—Trichophyton rubrum and Trichophyton mentagrophytes—is primarily treated with regimens of topical and systemic antifungal medications. This study was undertaken to evaluate in vitro the efficacy of low-voltage direct current as an antifungal agent for treating onychomycosis. Agar plate cultures of T rubrum and T mentagrophytes were subjected to low-voltage direct current electrostimulation, and antifungal effects were observed as zones in the agar around the electrodes lacking fungal growth. Zones devoid of fungal growth were observed for T rubrum and T mentagrophytes around anodes and cathodes in a dose-dependent manner in the current range of 500 μA to 3 mA. Low-voltage direct current electrostimulation has great clinical potential for the treatment of onychomycosis and perhaps other superficial maladies of fungal etiology. (J Am Podiatr Med Assoc 94(6): 565–572, 2004)
Background: Fungal foot infection is a common superficial fungal infection and is recognized as an important public health problem. Related to the wearing of occlusive footwear, foot infection is usually caused by dermatophytes and nondermatophyte molds. Previous in vitro studies have demonstrated that zinc oxide nanoparticles (ZnO-NPs) have antimicrobial activity against fungi. This study, therefore, evaluated the ability of socks coated with ZnO-NPs to inhibit fungal growth in an in vitro model mimicking real-life situations.
Methods: Scale from patients with fungal foot infections was equally divided into three groups: control, plain socks, and ZnO-NP socks. The specimens in the control group were routinely fungal cultured, whereas in the plain sock and ZnO-NP sock groups, scale was incubated with plain socks and ZnO-NP socks, respectively, for 24 hours. After incubation, each piece of sock was cultured. The fungal culture results of the three groups were progressively evaluated for 4 weeks.
Results: From 31 specimens, the positive fungal culture results of the control, plain sock, and ZnO-NP sock groups were 100%, 64.5%, and 54.8%, respectively. Specimens incubated with plain socks (P = .001) or with ZnO-NP socks (P < .001) had a significant reduction in the number of positive fungal cultures compared with the control.
Conclusions: Plain socks and ZnO-NP socks significantly inhibited fungal growth relative to the control. The wearing of either plain socks or ZnO-NP socks can prevent fungal foot infection because these socks act as a barrier to the insoles of shoes.
Background: Historically recalcitrant to treatment, infection of the nail unit is a pervasive clinical condition affecting approximately 10% to 20% of the US population; patients present with both cosmetic symptomatology and pain, with subsequent dystrophic morphology. To date, the presumptive infectious etiologies include classically reported fungal dermatophytes, nondermatophyte molds, and yeasts. Until now, the prevalence and potential contribution of bacteria to the clinical course of dystrophic nails had been relatively overlooked, if not dismissed. Previously, diagnosis had largely been made by means of clinical presentation, although microscopic examinations (potassium hydroxide) of nail scrapings to identify fungal agents and, more recently, panel-specific polymerase chain reaction assays have been used to elucidate causative infectious agents. Each of these tools suffers from test-specific limitations.
Methods: Molecular-age medicine now includes DNA-based tools to universally assess any microbe or pathogen with a known DNA sequence. This affords clinicians with rapid DNA sequencing technologies at their disposal. These sequencing-based diagnostic tools confer the accuracy of DNA-level certainty, and concurrently obviate cultivation or microbial phenotypical biases.
Results: Using DNA sequencing-based diagnostics, the results in this article document the first identification and quantification of significant bacterial, rather than mycotic, pathogens to the clinical manifestation of dystrophic nails.
Conclusions: In direct opposition to the prevailing and presumptive mycotic-based causes, the results in this article invoke questions about the very basis for our current standards of care, including effective treatment regimens.
Efinaconazole 10% solution is a new triazole antifungal agent developed for the topical treatment of onychomycosis. This article reviews the pooled results of the two pivotal clinical trials of this drug that have been performed in the United States, Canada, and Japan.
The two studies of 1,655 patients were both double-blind, vehicle-controlled, parallel-group, randomized, multicenter studies designed to determine the efficacy and safety of efinaconazole 10% solution in the treatment of mild-to-moderate onychomycosis of the toenails caused by dermatophytes. Treatment was provided once daily for 48 weeks, and the primary end point was at week 52.
The combined results show a 56% mycologic cure rate compared with 17% for vehicle at week 52. Clinical treatment success was achieved in 43% of patients treated with efinaconazole 10% solution at follow-up (week 52). Clinical treatment success was achieved in 47% of patients. As expected for a topical agent, the use of efinaconazole 10% solution was found to be safe, with mild, transient irritation at the site of application reported as the most common adverse event.
The efficacy and safety profile of efinaconazole 10% solution suggests that it may represent an important advance in the topical treatment of onychomycosis. Further studies will help us better understand the role of this agent for the treatment of this widespread podiatric medical condition.
Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed. The efficacy of tavaborole is associated with its novel mechanism of action, whereby it inhibits the fungal leucyl-tRNA synthetase (LeuRS) enzyme. Because LeuRS is an essential component in fungal protein synthesis, inhibition of LeuRS ultimately leads to fungal cell death. Tavaborole is the first boron-based antifungal medication approved for the treatment of mild-to-moderate onychomycosis and presents patients with a new topical option. Previously, ciclopirox and efinaconazole were the only approved topical treatments for onychomycosis. This article details the properties that are at the core of the clinical benefits associated with tavaborole.
Onychomycosis is a fungal infection of the nail that can be caused by dermatophytes, yeasts, or nondermatophyte molds. To diagnose onychomycosis, a clinician must use the patient's history, physical findings, and diagnostic testing, which can include calcofluor white/potassium hydroxide (KOH) mount, fungal culture (FC), and periodic acid–Schiff (PAS) stain. Some insurance companies require authorization for antifungal medication and request laboratory results to confirm infection. We sought to compare the reliability of KOH, PAS, and FC diagnostic results for confirmation of fungal disease, to determine the sensitivity and specificity of each test, and to investigate the cost of each test. In addition, we statistically observed the relationship between the test results and demographic variables.
Toenail clippings were obtained from 108 patients clinically diagnosed as having onychomycosis. Diagnostic tests were then performed on each sample; the results were obtained from medical records.
For PAS, KOH, and FC, 60.2%, 43.5%, and 39.8% of results, respectively, were positive. Agreement for each pair of tests was slightly higher for FC and KOH. Sensitivities for KOH and PAS were 0.64 and 0.79, respectively. Specificity was 0.79 for KOH and 0.54 for PAS. Both PAS and KOH had a higher percentage of positive test results for men than for women.
Of the three tests evaluated, PAS gives the most consistent positive results and has the highest sensitivity. Therefore, PAS should be considered as the best test to verify clinically significant onychomycosis.
Ciclopirox 8% nail lacquer is a recently introduced topical formulation of the hydroxypyridone antimycotic ciclopirox. In vitro data indicate that ciclopirox has activity against the important pathogenic dermatophytes responsible for onychomycosis. The lacquer delivery system provides a high concentration gradient for the transfer of the antifungal agent through the nail plate. Daily application to the toenail surface of healthy subjects resulted in good penetration and distribution within all nail layers. Systemic absorption of ciclopirox in five patients with onychomycosis was minimal.