Number of Affected Nails Is the Primary Determinant of Efinaconazole 10% Solution Usage for Onychomycosis.

Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112.    doi:10.36849/JDD.7676.

The Peer Review System: A Journal Editor's 30-Year Perspective.

The peer review system has become the standard by which scientific articles are refereed. Unfortunately, even from its beginnings in the mid-1800s it has been fraught with difficulties. Potential reviewers are volunteers who may be inundated with requests to review yet these reviews take considerable time and effort. There is little motivation to complete a review causing significant delays in the publication process. There may be biases unintentionally built into the system between reviewers, authors, editors, and journals. Attempts to overcome these biases by various blinding schemes have been met with limited success. Finally, the recent advent of Artificial Intelligence has the potential to completely upend the system, for good or bad.

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.

Parenteral Vancomycin in the Treatment of MRSA-Associated Diabetic Foot Infections: An Unnecessary Risk.

Diabetic foot infections (DFIs) are a common and costly complication of diabetes. Soft tissue and bone infections in DFIs frequently lead to amputation and/or sepsis which can be costly for both the patient and the healthcare system. Staphylococcus aureus is the most commonly identified causative agent in DFIs, and people with diabetes may have an increased risk of infection with methicillin-resistant Staphylococcus aureus (MRSA). In addition to increased susceptibility to severe infection, MRSA in DFIs is associated with high rates of treatment failure, morbidity, and hospitalization costs meaning appropriate treatment is a high priority. While hospitalized patients are usually treated with intravenous (IV) vancomycin, this can be costly in terms of inpatient stays, staffing costs, and adverse events. For example, vancomycin-associated acute kidney injury not only delays hospital discharge and increases costs but is also a particular concern for patients with diabetes who already have an increased risk of kidney problems. Vancomycin-resistant strains of S. aureus have also been identified, which means that alternative treatment options may need to be explored. Treatment alternatives to IV vancomycin, including oral antibiotics, have been shown to provide similar efficacy, with reduced costs, outpatient or home-based administration, and with fewer serious adverse effects. Although infectious disease specialists often use IV vancomycin alone, or in combination, as a first-line therapeutic option, they are increasingly seeing the value of outpatient or at-home oral antibiotics as an alternative. This manuscript reviews the evidence for true costs of vancomycin therapy for MRSA-associated DFIs and examines the alternatives.

Topical autologous blood clot therapy: consensus panel recommendations to guide use in the treatment of complex wound types.

The etiology of acute and chronic wounds goes beyond those often reported in the literature, including those with exposed structures, those in which the entire wound bed cannot be visualized, and patients who are not candidates for typical standard of care. Treatment options for these patients may be limited. TABCT is a viable option for these complex wound types and is not hindered by logistical, procedural, or patient factors. A consensus panel of providers with extensive experience in treatment of these wound types was convened to develop consensus recommendations on the use of TABCT in specific complex wound types. Four consensus statements were defined for TABCT use in patients who cannot undergo sharp or extensive debridement, as a protective barrier to prevent further bacterial ingress, in patients with wounds in which the entire wound bed cannot be safely visualized, and in wounds with exposed tendon and/or bone. Consensus panel recommendations show that TABCT application assists in maintenance of a moist wound healing environment, autolytic debridement, recruitment and delivery of factors essential for wound healing, prevention of pathogen entry, and ability to completely fill wound voids that cannot be fully visualized. Additional advantages of TABCT use are its cost-effectiveness, ease of access, minimal related complications, and proven clinical efficacy.

All Feet on Deck: The Role of Podiatry During the COVID-19 Pandemic: Preventing Hospitalizations in an Overburdened Health-Care System, Reducing Amputation and Death in People with Diabetes.

The coronavirus disease of 2019 pandemic is driving significant change in the health-care system and disrupting the best practices for diabetic limb preservation, leaving large numbers of patients without care. Patients with diabetes and foot ulcers are at increased risk for infections, hospitalization, amputations, and death. Podiatric care is associated with fewer diabetes-related amputations, emergency room visits, hospitalizations, length-of-stay, and costs. However, podiatrists must mobilize and adopt the new paradigm of shifts away from hospital care to community-based care. Implementing the proposed Pandemic Diabetic Foot Triage System, in-home visits, higher acuity office visits, telemedicine, and remote patient monitoring can help podiatrists manage patients while reducing the coronavirus disease of 2019 risk. The goal of podiatrists during the pandemic is to reduce the burden on the health-care system by keeping diabetic foot and wound patients safe, functional, and at home.

Topical autologous blood clot therapy: an introduction and development of consensus panel to guide use in the treatment of complex wound types.

Complex or hard-to-heal wounds can be acute or chronic; the complexity is based on patient-specific local, systemic, and psychosocial factors. Use of autologous tissue can be a significant adjunct to wound closure. Grafts and flaps are the most common autologous tissue used in wound reconstruction. However, patient factors, wound size, and exposed structures may preclude using these methods as primary or even secondary closure techniques. Alternative autologous tissue therapies include those derived from adipose, epidermis or dermis, bone marrow, and blood. Limitations of these treatment modalities include access-related difficulty, cost, creation of a secondary donor site, use of singular or limited cell types, and sparse or contradictory evidence basis of their efficacy of use. A panel of providers experienced in wound care and surgical wound management was convened to create a series of publications on the use of topical autologous blood clot therapy (TABCT) in the treatment of complex wounds. This publication, the first in a series, provides an evidence basis of the gap between definition and treatment of complex wounds, an overview of the use of autologous therapies in these wounds, and the science behind TABCT. The development of a consensus panel for decision pathways and recommendations for TABCT use in specific complex wound types are also discussed. Subsequent articles will provide consensus recommendations on the use of TABCT in full-thickness wounds with exposed tendon and/or bone and undermining or tunneling wounds, in wounds in patients who are nonsurgical candidates, in those who cannot undergo sharp debridement, in patients with arterial wounds who have been maximally revascularized, and in those with transsphincteric anal fistula. This article provides a foundation of knowledge and describes the plan for consensus panel decision pathways and recommendation development of use of TABCT in the treatment of specific complex wound types.

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US.

BACKGROUND: Onychomycosis affects around 14% of individuals in North America and Europe and is undertreated. Treatment is challenging as toenail growth can take 12–18 months, the nail plate may prevent drug penetration, and disease recurrence is common. National guidelines/consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago and updated medical guidance is needed. METHODS: This document aims to provide recommendations for the diagnosis and pharmaceutical treatment of toenail onychomycosis following a roundtable discussion with a panel of dermatologists, podiatrists, and a microbiologist specializing in nail disease. RESULTS: There was a general consensus on several topics regarding onychomycosis diagnosis, confirmatory laboratory testing, and medications. Onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture. Terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. Efinaconazole can also be considered for off-label use for maintenance to prevent recurrences. For optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment. CONCLUSIONS: This article provides important updates to previous guidelines/consensus documents to assist dermatologists and podiatrists in the diagnosis and treatment of toenail onychomycosis. J Drugs Dermatol. 2021;20(10):1076-1084. doi:10.36849/JDD.6291.

A Standardized Approach to Evaluating Lower Extremity Chronic Wounds Using a Checklist.

As the population ages and more people live with diabetes, obesity, and vascular disease, chronic wounds have become more prevalent. Increasingly, wound care falls into the hands of clinicians who may be new to the specialty. To facilitate a better understanding of wounds and to ensure all integral items for best outcomes are considered, an interprofessional panel of wound care experts developed a checklist to aid in lower extremity wound identification, assessment, evaluation, and potential complication recognition. This checklist focuses on an evidence-based approach to obtaining a medical history, evaluating the wound, determining the etiology, and assessing perfusion, edema, infection, and neurologic status. The goal of this fundamental evaluation tool is to help the clinician move towards the next steps in optimizing patient care. Evidence-based support for each item on the checklist is reviewed and detailed for clinician reference.

Clinical trial designs for topical antifungal treatments of onychomycosis and implications on clinical practice.

There currently are 3 topical agents approved by the US Food and Drug Administration (FDA) to treat onychomycosis: tavaborole, efinaconazole, and ciclopirox. The phase 3 clinical trial designs for these treatments and their notable differences make it difficult for clinicians to interpret the data into clinical practice. For example, the primary end point predominantly used to assess efficacy in all the trials is complete cure, defined as no involvement of the nail plus mycologic cure; also, a notable number of patients fail to achieve a complete cure despite clear improvement in the nail. Despite close similarities in the end points and overall design of the clinical trials used for these agents, differences in design are notable, including the age range of participants, the range of mycotic nail involvement, the presence/absence of tinea pedis, and the nail trimming/debridement protocols used. The differences in clinical trial designs for the 3 FDA-approved topical agents and the lack of head-to-head studies makes efficacy interpretation and comparison inappropriate. This article reviews the phase 3 clinical trials that led to FDA approval of these agents, focusing on their similarities and differences.

A Proposed New Classification of Skin and Soft Tissue Infections Modeled on the Subset of Diabetic Foot Infection.

Schemes for classifying skin and soft tissue infections (SSTIs) pose limitations for clinicians and regulatory agencies. Diabetic foot infections (DFIs) are a subset of SSTIs. We developed and are proposing a classification to harmonize current schemes for SSTIs and DFIs. Existing schemes for classifying SSTIs are limited in both their usefulness to clinicians and to regulatory agencies. The guidelines on SSTI from the Infectious Diseases Society of America (IDSA) and the guidance from the US Food and Drug Administration do not adequately address many types of wound infections. However, guidelines developed by the IDSA for DFIs provide a classification scheme that has been validated and widely used. Diabetic foot infections are similar to SSTIs in pathophysiology, microbiology, and treatment and can be seen as a subset of SSTI. Thus, based on the documents noted above, and our review of the literature, we have developed a proposed classification scheme for SSTI that harmonizes well with the DFI classification. We believe this new scheme will assist clinicians in classifying most wound infections and potentially aid regulatory agencies in testing and approving new antimicrobials for these infections.

Tedizolid and Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections of the Lower Extremity versus Non-Lower-Extremity InfectionsPooled Analysis of Two Phase 3 Trials.

BACKGROUND: Tedizolid phosphate, the prodrug of the oxazolidinone tedizolid, has been approved in a number of countries, including the United States, those in the European Union, and Canada, for treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Two phase 3 trials demonstrated the noninferior efficacy of tedizolid (200 mg once daily for 6 days) to linezolid (600 mg twice daily for 10 days) in patients with ABSSSI. Because of the challenges of treating lower-extremity ABSSSI, the efficacy and safety of tedizolid and linezolid for treating lower-extremity versus non-lower-extremity infections were compared. METHODS: This was a post hoc analysis of pooled data from patients with lower-extremity infections enrolled in two phase 3 studies, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing tedizolid to linezolid in patients with ABSSSI. RESULTS: Lower-extremity ABSSSI were present in 40.7% of tedizolid-treated and 42.2% of linezolid-treated patients. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 34.7% of all patients with a baseline causative pathogen. Early clinical responses at 48 to 72 hours and investigator-assessed responses at the post-therapy evaluation were similar between tedizolid and linezolid, regardless of ABSSSI type. With both treatments, the early clinical response was slightly higher in patients with non-lower-extremity infection than in those with lower-extremity ABSSSI (tedizolid, 84.8% versus 77.0%; linezolid, 81.4% versus 76.6%, respectively); however, by the post-therapy evaluation visit, response rates were similar (tedizolid, 87.1% versus 86.3%; linezolid, 86.6% versus 87.2%, respectively). Gastrointestinal adverse events and low platelet counts were observed more frequently with linezolid treatment. CONCLUSIONS: Post-therapy evaluations showed that the clinical response of lower-extremity ABSSSI to tedizolid and linezolid was comparable to that of ABSSSI in other locations. A short 6-day course of once-daily tedizolid was as effective as a 10-day course of twice-daily linezolid in treating patients with lower-extremity ABSSSI.

Diagnosis and Management of Onychomycosis Perspectives from a Joint Podiatric Medicine-Dermatology Roundtable.

Onychomycosis is a fungal infection, and, as such, one of the goals of treatment should be eradication of the infective agent. Despite this, in contrast to dermatologists, many podiatric physicians do not include antifungals in their onychomycosis treatment plans. Before initiating treatment, confirmation of mycologic status via laboratory testing (eg, microscopy with potassium hydroxide preparation, histopathology with periodic acid-Schiff staining, fungal culture, and polymerase chain reaction) is important; however, more podiatric physicians rely solely on clinical signs than do dermatologists. These dissimilarities may be due, in part, to differences between specialties in training, reimbursement patterns, or practice orientation, and to explore these differences further, a joint podiatric medicine-dermatology roundtable was convened. In addition, treatment options have been limited owing to safety concerns with available oral antifungals and relatively low efficacy with previously available topical treatments. Recently approved topical treatments-efinaconzole and tavaborole-offer additional options for patients with mild-to-moderate disease. Debridement alone has no effect on mycologic status, and it is recommended that it be used in combination with an oral or topical antifungal. There is little to no clinical evidence to support the use of lasers or over-the-counter treatments for onychomycosis. After a patient has achieved cure (absence of clinical signs or absence of fungus with minimal clinical signs), lifestyle and hygiene measures, prophylactic/maintenance treatment, and proactive treatment for tinea pedis, including in family members, may help maintain this status.

Diagnosis and Management of Onychomycosis: Perspectives from a Joint Podiatry-Dermatology Roundtable.

Onychomycosis is a fungal infection, and, as such, one of the goals of treatment should be eradication of the infective agent. Despite this, in contrast to dermatologists, many podiatric physicians do not include antifungals in their onychomycosis treatment plans. Before initiating treatment, confirmation of mycologic status via laboratory testing (eg, microscopy with potassium hydroxide preparation, histopathology with periodic acid-Schiff staining, fungal culture, and polymerase chain reaction) is important; however, more podiatric physicians rely solely on clinical signs than do dermatologists. These dissimilarities may be due, in part, to differences between specialties in training, reimbursement patterns, or practice orientation, and to explore these differences further, a joint podiatric medicine-dermatology roundtable was convened. In addition, treatment options have been limited owing to safety concerns with available oral antifungals and relatively low efficacy with previously available topical treatments. Recently approved topical treatments-efinaconzole and tavaborole-offer additional options for patients with mild-to-moderate disease. Debridement alone has no effect on mycologic status, and it is recommended that it be used in combination with an oral or topical antifungal. There is little to no clinical evidence to support the use of lasers or over-the-counter treatments for onychomycosis. After a patient has achieved cure (absence of clinical signs or absence of fungus with minimal clinical signs), lifestyle and hygiene measures, prophylactic/maintenance treatment, and proactive treatment for tinea pedis, including in family members, may help maintain this status.

Onychomycosis Diagnosis and Management: Perspectives from a Joint Dermatology-Podiatry Roundtable.

Onychomycosis prevalence is expected to rise as the population ages and the prevalence of diabetes, peripheral vascular disease, and other significant risk factors rise. Until recently, treatment options were limited due to safety concerns with oral antifungals and low efficacy with available topical agents. Efinaconzole and tavaborole were approved by the FDA in 2014 for onychomycosis treatment and provide additional effective topical treatment options for patients with mild-to-moderate disease. Dermatologists and podiatrists both regularly treat onychomycosis, yet there are striking differences between specialties in approach to diagnosis and treatment. In order to explore these differences a joint dermatology-podiatry roundtable of onychomycosis experts was convened. Although it has little effect on mycologic cure, debridement may be a valuable adjunct to oral or topical antifungal therapy, especially in patients with greater symptom burden. However, few dermatologists incorporate debridement into their treatment plans and referral to podiatry may be appropriate for some of these patients. Furthermore, podiatrists may be better equipped to manage patients with concurrent diabetes or peripheral vascular disease and elderly patients who are unable to maintain proper foot hygiene. Once cure is achieved, lifestyle and hygiene practices, maintenance/prophylactic onychomycosis treatment, and proactive tinea pedis treatment in patients and family members may help to maintain patients' cured status.