Search Results
Efinaconazole Topical Solution, 10%
The Development of a New Topical Treatment for Toenail Onychomycosis
Background
Toenail onychomycosis is a common disease with limited treatment options; treatment failure and relapse are frequently encountered. Many patients experience long-standing disease affecting multiple toenails, with substantial discomfort and pain. Although some patients might prefer a topical therapy, efficacy with ciclopirox nail lacquer has been disappointing.
Methods
Efinaconazole topical solution, 10% is the first topical triazole antifungal agent specifically developed for the treatment of onychomycosis. This paper reviews the preclinical and clinical data on efinaconazole topical solution, 10%.
Results
Efinaconazole has a broad spectrum of antifungal activity in vitro and is more potent than ciclopirox against common onychomycosis pathogens. It has a more optimal keratin affinity than ciclopirox, and it exhibits significantly greater in vivo activity owing to its superior nail penetration. Mycologic cure rates at week 52 were 55.2% (study 1) and 53.4% (study 2) with efinaconazole topical solution, 10% compared with 16.8% and 16.9%, respectively, with vehicle (P<.001 for both). In addition, efinaconazole is well tolerated.
Conclusions
Efinaconazole topical solution, 10% may likely become a preferred topical agent for the management of mild-to-moderate onychomycosis.
Background
Regarding antibiotic-loaded cements, there is an abundant amount of literature regarding the antibacterial in vitro inhibitory and clinical applications for the treatment of osteomyelitis. The opposite can be said about literature regarding in vitro antifungal-loaded cement drug delivery for the treatment of fungal osteomyelitis.
Methods
Aspergillus fumigatus and Candida (ATCC 1023ATCC, Manassas, Virginia) were plated on antibiotic/antifungal-free plates. Voriconazole- and amphotericin B–impregnated calcium sulfate and hydroxyapatite (HA) disks, calcium sulfate + HA control disks, and control polymethylmethacrylate disks were laid separately onto plates separately inoculated with Aspergillus and Candida spp. The zones of inhibition obtained were measured in millimeters at 24, 36, and 96 hours.
Results
Etest (bioMérieux, Marcy l'Etoile, France) results demonstrated susceptibility of Aspergillus and Candida to amphotericin B and voriconazole. The zone of inhibition data demonstrated that voriconazole and amphotericin B retained their antifungal activity when mixed into the calcium sulfate + HA bone void filler and eluted at biologically effective antifungal concentrations over 96 hours.
Conclusions
The calcium sulfate + HA bone void filler is a biocompatible ceramic carrier vehicle that can successfully deliver the antifungal drugs voriconazole and amphotericin B in the adjunctive treatment of fungal osteomyelitis. It is a reliable strategy in the local delivery of antifungal drugs to an area of osteomyelitis.
Background
Charcot's neuroarthropathy (CN) treatment is still controversial, and the results are controversial. Owing to patient comorbidities, surgical intervention carries a high risk of complications. Thus, foreseeing the possible results of planned treatment is crucial. We retrospectively evaluated the Charcot Reconstruction Preoperative Prognostic Score (CRPPS) in patients with surgically treated CN.
Methods
Twenty-two feet of 20 patients were included in the study. Two groups were formed according to their CRPPS. Twelve patients with values less than 4 were defined as group A, and eight patients with values of 4 or greater were defined as group B. Mean follow-up was 61 months (range, 5–131 months). Groups were compared according to American Orthopaedic Foot and Ankle Society (AOFAS) scores, Foot and Ankle Disability Index (FADI) scores, and complication rates.
Results
Group A and B mean AOFAS scores were 76.83 (range, 71–85) and 70.5 (range, 20–85), respectively. All of the patients were improved according to AOFAS and FADI scores, but no correlation was found with the CRPPS. None of the group A patients required additional intervention, but five patients in group B underwent revision surgery. No amputations were performed.
Conclusions
The CRPPS is focused on feasibility. The data needed to fill the scoring system is easily obtainable from medical records even retrospectively, and the score is helpful to predict a patient's outcome after CN-related surgery. Herein, CRPPS values of 4 or greater were related to high complication rates and lower functional outcomes.
The Management of Diabetic Foot Ulcers Through Optimal Off-Loading
Building Consensus Guidelines and Practical Recommendations to Improve Outcomes
Background
We sought to develop a consensus statement for the use of off-loading in the management of diabetic foot ulcers (DFUs).
Methods
A literature search of PubMed for evidence regarding off-loading of DFUs was initially conducted, followed by a meeting of authors on March 15, 2013, in Philadelphia, Pennsylvania, to draft consensus statements and recommendations using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to assess quality of evidence and develop strength of recommendations for each consensus statement.
Results
Evidence is clear that adequate off-loading increases the likelihood of DFU healing and that increased clinician use of effective off-loading is necessary. Recommendations are included to guide clinicians on the optimal use of off-loading based on an initial comprehensive patient/wound assessment and the necessity to improve patient adherence with off-loading devices.
Conclusions
The likelihood of DFU healing is increased with off-loading adherence, and, current evidence favors the use of nonremovable casts or fixed ankle walking braces as optimum off-loading modalities. There currently exists a gap between what the evidence supports regarding the efficacy of DFU off-loading and what is performed in clinical practice despite expert consensus on the standard of care.
External thermoregulation using noncontact normothermic wound therapy accelerates wound closure by second intention in areas of existing osteomyelitis before surgical excision compared with standard wound care. This pilot study consisted of two arms. The control arm received standard wound care, which resulted in complete ulcer healing at an average of 127 days. The treatment arm received noncontact normothermic wound therapy, which resulted in complete ulcer healing at an average of 59 days, or 54% faster than in the control arm. This new treatment allows the physician to decrease the rate of limb loss and recurrent osteomyelitis by decreasing the morbidity of bone reinfection through the wound bed. There have been no published studies or case presentations addressing thermoregulation in the management of wounds associated with osteomyelitis. Although noncontact normothermic wound therapy is not a direct treatment for osteomyelitis, this new treatment option results in significantly accelerated healing of wounds associated with osteomyelitis. (J Am Podiatr Med Assoc 93(1): 18-22, 2003)
Efinaconazole Topical Solution, 10%
Efficacy in Patients with Onychomycosis and Coexisting Tinea Pedis
Background
We sought to evaluate the efficacy of efinaconazole topical solution, 10%, in patients with onychomycosis and coexisting tinea pedis.
Methods
We analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Three groups were compared: patients with onychomycosis and coexisting interdigital tinea pedis on-study (treated or left untreated) and those with no coexisting tinea pedis.
Results
Treatment with efinaconazole topical solution, 10%, was significantly more effective than vehicle use irrespective of the coexistence of tinea pedis or its treatment. Overall, 352 patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis, with 215 of these patients (61.1%) receiving investigator-approved topical antifungal agents for their tinea pedis in addition to their randomized onychomycosis treatment. At week 52, efinaconazole complete cure rates of 29.4% were reported in patients with onychomycosis when coexisting tinea pedis was treated compared with 16.1% when coexisting tinea pedis was not treated. Both cure rates were significant compared with vehicle (P = .003 and .045, respectively), and in the latter subgroup, no patients treated with vehicle achieved a complete cure.
Conclusions
Treatment of coexisting tinea pedis in patients with onychomycosis enhances the efficacy of once-daily topical treatment with efinaconazole topical solution, 10%.
Diagnosis and Prevalence of Onychomycosis in Diabetic Neuropathic Patients
An Observational Study
Background: An observational study was conducted to assess the prevalence of onychomycosis in clinically suspected diabetic neuropathic patients and to assess the reliability of the diagnosis.
Methods: One hundred successive type 1 and 2 diabetic patients with diabetic neuropathy were followed. Diabetic neuropathy was defined by a vibration perception threshold greater than 25 V and onychomycosis by clinical diagnosis. Samples of the most affected nail were taken. Potassium hydroxide testing and culture were performed. Photographs of the nails were used by two dermatologists for diagnosis.
Results: The mean ± SE age was 62.3 ± 11.4 years for the 20 onychomycotic patients and 60.3 ± 10.4 years for the entire cohort; 14 onychomycotic patients (70%) were male versus 56 in the full cohort (56%) (P < .05). The prevalence of onychomycosis was 20% (culture and potassium hydroxide test positive) and 24% (culture positive). Twenty or 30 patients were positive by the potassium hydroxide test, depending on the investigator. The most frequent pathogen found was Trichophyton rubrum (11 of 20 patients; 55%). The positive predictive values of the dermatologist’s diagnoses were 57.8% and 35.6%, and the negative predictive values were 85.0% and 90.5%. The two expert’s results were significantly different (P < .05).
Conclusions: The diagnosis of onychomycosis is difficult to make. The diagnostic methods commonly used are not satisfactory. If onychomycosis is dangerous for the diabetic foot, a better diagnostic method is needed. (J Am Podiatr Med Assoc 99(2): 135–139, 2009)
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
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.
Methods
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.
Results
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.
Conclusions
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.
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)
