Work

Concerning rates of laboratory‐confirmed antifungal‐resistant onychomycosis and tinea pedis: An online survey of podiatrists, United States

Year: 2023

Type: article

Abstract: Onychomycosis (tinea unguium) and tinea pedis are common, frequently concomitant infections of the nails and feet, respectively, and are often caused by dermatophyte fungi (Trichophyton, Microsporum, and Epidermophyton spp.).1 Antifungal-resistant tinea is an emerging global public health problem.2 A recent, large analysis of toenail samples from US patients with suspected onychomycosis found that nearly 4% of Trichophyton spp samples had squalene epoxidase gene mutations, which are associated with terbinafine resistance.3 Clinicians may be increasingly likely to encounter resistant tinea infections. Therefore, we aimed to assess diagnostic approaches, antifungal resistance testing practices, and treatment practices for treatment-resistant onychomycosis and tinea pedis. A 12-question survey was developed in early 2023 by a working group consisting of a dermatologist with expertize in cutaneous fungal infections (BE), an infectious disease clinician (PP), infectious diseases laboratory scientists, epidemiologists, and other experts. The survey instrument was created using QualtricsXM licensed to The Ohio State University (CTJ). The survey was deemed exempt from full review by the university's Institutional Review Board. Informed consent was included as the initial segment of the survey which gave access to the subsequent survey questions when affirmed. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq.). The survey aimed to query a range of physicians, including podiatrists, who treat dermatophyte infections; the survey was emailed twice to approximately 8000 nonstudent and nonresident American Podiatric Medical Association (APMA) members in February 2023. Other distribution listservs included: dermatologists, the Mycoses Study Group Education and Research Consortium, the FungusCME.org listserv, and social media. SAS (SAS Institute, v. 9.4) was used to produce descriptive statistics. The survey closed on March 31, 2023, with 577 responses. Most responses (n = 498, 86.3%) were from podiatrists, 19 were from primary care practitioners, 23 were from dermatologists, 19 (3.3%) were from infectious diseases physicians, 13 (2.3%) from others, and 5 (0.9%) from pathology/laboratory medicine clinicians. The quantity and completeness of responses from the non-podiatry audiences were low; therefore, we focused on the responses from podiatrists to preserve statistical power. In total, 498 podiatrists began the survey; 200 respondents who did not complete the survey and 1 who did not see patients with dermatophyte infections were excluded from the analysis. Among the 297 included respondents, 106 (36.9%) were from the South; 83 (28.9%) were from the Northeast; 55 (19.2%) were from the Midwest, and 43 (15.0%) were from the West. Most respondents (n = 266, 89.6%) saw > 10 patients with onychomycosis and >10 patients with tinea pedis monthly (n = 171, 57.6%) (Figure 1). The most commonly reported definitions of treatment failure were terbinafine failure (72.4%), failure of multiple topical therapies (71.4%), and infection spreading during treatment (48.1%) (Table 1). Most respondents (53.2%) reported that >20% of onychomycosis cases involve treatment failure; 52.2% reported that <10% of tinea pedis cases involved treatment failure (Figure 2). Cost was a frequently reported (59.6%) barrier to ordering diagnostic testing for dermatophyte infections. The most commonly ordered diagnostic testing included histological examination (81.5%) and molecular testing (59.5%); 21.6% ordered antifungal susceptibility testing, and 30.0% indicated that their laboratory has reported antifungal resistance for treatment failure cases. No regional differences in antifungal resistance were observed (data not shown). For difficult-to-treat or terbinafine-resistant dermatophyte cases, reported management strategies included surgical nail avulsion (59.6%), topical therapy (45.8%), and systemic azole therapy (39.1%) (Figure 3). However, 31.0% reported that some cases remained refractory. Our study demonstrates that antifungal resistant onychomycosis and tinea pedis might be more common than previously appreciated, with nearly one-third of surveyed podiatrists reporting laboratory-confirmed resistance. This proportion might underestimate the true frequency of antifungal resistance because nearly 80% of podiatrists did not routinely order antifungal susceptibility testing. In addition, our study highlights the burden of onychomycosis, as suggested by the high percentage of onychomycosis patients who experience treatment failure, and by the substantial percentage of whom underwent surgical nail avulsion, which is painful and unlikely to be curative. The proportion of podiatrists reporting antifungal resistance in this survey exceeded a 2022 survey in which nearly 20% of 1500 nonspecialist healthcare providers reported clinical experience with antifungal resistant tinea.4 These findings might be attributable to podiatrists ordering diagnostic testing for suspected tinea more frequently than nonspecialists.5 For all clinicians who see patients with tinea, confirmatory laboratory testing is essential for guiding appropriate therapy and avoiding unnecessary antifungal use. Reported treatment failure in this study could be related to several factors besides resistance, including misdiagnosis, patient non-adherence to treatment, or variable definitions of treatment failure. For suspected onychomycosis, the differential is broad, and approximately half of nail disorders seen in clinical practice are not due to fungal pathogens.1 Therefore, the American Academy of Dermatology, as part of the ABIM Foundation's Choosing Wisely campaign, recommends that suspected fungal nail infections be confirmed before starting oral antifungal therapy,6 which we argue should be expanded to include topical antifungals. In addition, inadequate courses of antifungal therapy can lead to treatment failure, particularly for onychomycosis, which requires a long treatment course and can be difficult to completely cure. A treat-to-terminate approach is suggested. The high proportion of laboratory-confirmed antifungal resistance observed could also partly reflect survey response bias in which APMA members who were more familiar with dermatophytes and resistance were more likely to respond to the survey. Other study limitations include that we did not query regarding laboratory-confirmed antifungal resistance for tinea pedis and onychomycosis separately, though tinea pedis almost always precedes onychomycosis. The lack of demographic and training-related information for respondents is another notable limitation. These data could help identify more specific opportunities to address educational gaps in antifungal resistance testing practices. Together with previous studies, our findings suggest that antifungal-resistant tinea is a growing concern. This concern merits increased attention to antifungal stewardship efforts, emphasizing diagnostic testing and judicious antifungal use for suspected superficial fungal infections of the skin and nails. Kaitlin Benedict: Formal analysis; writing—original draft; writing—review and editing. Jeremy A. W. Gold: Conceptualization; methodology; writing—review and editing. Carolynn T. Jones: Conceptualization; methodology; writing—review and editing. Lisa A. Tushla: Conceptualization; methodology; writing—review and editing. Shari R. Lipner: Methodology; writing—review and editing. warren s joseph: writing—review and editing. Dyane E. Tower: Writing—review and editing. Boni Elewski: Conceptualization; methodology; writing—review and editing. Peter G. Pappas: Conceptualization; methodology; supervision; writing—review and editing. This survey was funded in at by a cooperative agreement with the Centers for Disease Control and Prevention (CDC-RFA-CK20-2003) to the University of Alabama at Birmingham and in collaboration with Terranova Medical LLC and The Mycoses Study Group Education and Research Consortium. Shari Lipner has served as a consultant for Ortho-Dermatologics, Moberg Pharmaceuticals, Hoth Therapeutics, and BelleTorus Corporation. Lisa Tushla has received research grant support from Bristol Myers Squibb and Novartis in the area of skin cancer. These financial relationships were not involved with this study. The remaining authors declare no conflict of interest. The lead author Kaitlin Benedict affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. The data presented in this study are primarily included in this article; however, the full data set and survey instrument may be available on request from the corresponding author.

Source: Health Science Reports

DOI: 10.1002/hsr2.1694