Combatting antifungal resistance: Paradigm shift in the diagnosis and management of onychomycosis and dermatomycosis

Abstract

Antifungal resistance has become prevalent worldwide. Understanding the factors involved in spread of resistance allows the formulation of strategies to slow resistance development and likewise identify solutions for the treatment of highly recalcitrant fungal infections. To investigate the recent explosion of resistant strains, a literature review was performed focusing on four main areas: mechanisms of resistance to antifungal agents, diagnosis of superficial fungal infections, management, and stewardship. The use of traditional diagnostic tools such as culture, KOH analysis and minimum inhibitory concentration values on treatment were investigated and compared to the newer techniques such as molecular methods including whole genome sequencing, and polymerase chain reaction. The management of terbinafine‐resistant strains is discussed. We have emphasized the need for antifungal stewardship including increasing surveillance for resistant infection.

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

“…Toenail dystrophy has several aetiologies with clinical presentations that may be mistaken for onychomycosis, underlining the need for differential diagnosis to both rule out non‐fungal causes and to confirm the presence of fungal infection prior to the initiation of treatment 68,69 . One of the central tenants of good antifungal stewardship is that the diagnosis of a fungal infection be confirmed prior to initiating treatment 70 . However, antifungal drugs are often prescribed empirically, without testing to confirm the presence and identity of a causative fungal organism, and treatment failure may be followed by additional empiric prescription of other antifungal drugs 69,71 .…”

“…Elements of antifungal stewardship. There are seven vital components of any antifungal stewardship programme 70 . Among the key components are improvements in education, broader implementation of confirmatory and susceptibility testing (and other appropriate testing, such as SQLE gene mutational analysis) to guide antifungal treatment, and monitoring of clinical and antimicrobial resistance.…”

“…68,69 One of the central tenants of good antifungal stewardship is that the diagnosis of a fungal infection be confirmed prior to initiating treatment. 70 However, antifungal drugs are often prescribed empirically, without testing to confirm the presence and identity of a causative fungal organism, and treatment failure may be followed by additional empiric prescription of other antifungal drugs. 69,71 Treatment of a non-fungal disorder with an antifungal agent unnecessarily exposes the patient to adverse drug effects and may allow for worsening of their condition.…”

“…Antifungal stewardship describes the principle of maximizing treatment outcomes for patients while maintaining the effectiveness of antifungal treatment options, and involves activities ranging from coordinated global monitoring of antifungal usage and resistance to decisions made by individual physicians and patients (Figure 5). 5,70 Globally and nationally, development of guidelines, improvements in epidemiological surveillance, increased access to diagnostic capabilities and greater availability of antifungal drugs are needed 47 . To this end, in 2022 the CDC issued a call for proposals for projects to assess the burden of antifungal‐resistant dermatophyte infections in the United States in order to inform public health prevention efforts, shape clinical guidelines, guide policy, and to better understand the molecular epidemiology and emergence of resistant dermatophyte strains 83 .…”

“…inadvertently increase the longevity and severity of the underlying infection, as approval for their use requires only meeting the standard of 'temporary increase in clear nail' without the need to demonstrate any mycological effects 81. 4 | COUNTER AC TING RE S IS TAN CE THROUG H ANTIFUNG AL S TE WARDS HIPIncreasing rates of treatment failure with first-line antifungal therapies demands more responsible antifungal usage and monitoring of antifungal resistance.5,67,82 Antifungal stewardship describes the principle of maximizing treatment outcomes for patients while maintaining the effectiveness of antifungal treatment options, and involves activities ranging from coordinated global monitoring of antifungal usage and resistance to decisions made by individual physicians and patients (Figure5).5,70 Globally and nationally, development of guidelines, improvements in epidemiological surveillance, increased access to diagnostic capabilities and greater availability of antifungal drugs are needed 47. To this end, in 2022 the CDC issued a call for proposals for projects to assess the burden of antifungalresistant dermatophyte infections in the United States in order to inform public health prevention efforts, shape clinical guidelines, guide policy, and to better understand the molecular epidemiology and emergence of resistant dermatophyte strains 83.…”