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      ­­­­­­Topical Antifungal Prescribing for Medicare Part D Beneficiaries — United States, 2021

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          Notes from the Field: First Reported U.S. Cases of Tinea Caused by Trichophyton indotineae — New York City, December 2021–March 2023

          Tinea is a common, highly contagious, superficial infection of the skin, hair, or nails caused by dermatophyte molds.* During the past decade, an epidemic of severe, antifungal-resistant tinea has emerged in South Asia because of the rapid spread of Trichophyton indotineae, † a novel dermatophyte species; the epidemic has likely been driven by misuse and overuse of topical antifungals and corticosteroids § ( 1 , 2 ). T. indotineae infections are highly transmissible and characterized by widespread, inflamed, pruritic plaques on the body (tinea corporis), the crural fold, pubic region, and adjacent thigh (tinea cruris), or the face (tinea faciei) ( 1 ). T. indotineae isolates are frequently resistant to terbinafine, a mainstay of tinea treatment ( 1 , 3 ). T. indotineae infections have been reported throughout Asia and in Europe and Canada but have not previously been described in the United States ( 3 ). On February 28, 2023, a New York City dermatologist notified public health officials of two patients who had severe tinea that did not improve with oral terbinafine treatment, raising concern for potential T. indotineae infection; these patients shared no epidemiologic links. Skin culture isolates from each patient were previously identified by a clinical laboratory as Trichophyton mentagrophytes and were subsequently forwarded to the Wadsworth Center, New York State Department of Health, for further review and analysis. Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis performed during March 2023, identified the isolates as T. indotineae (Supplementary Figure; https://stacks.cdc.gov/view/cdc/127678). Activity related to this investigation was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. ¶ Patient A, a woman aged 28 years, developed a widespread pruritic eruption during summer 2021. She had a first dermatologic evaluation in December 2021, at which time she was in her third trimester of pregnancy. She had no other underlying medical conditions, no known exposures to a person with similar rash, and no recent international travel history. Dermatologists noted large, annular, scaly, pruritic plaques over the neck, abdomen, pubic region, and buttocks (Figure). She received a diagnosis of tinea and began oral terbinafine therapy in January 2022 after the birth of her baby. Because her eruptions did not improve after 2 weeks of therapy, terbinafine was discontinued, and she began itraconazole treatment. The rash resolved completely after completing a 4-week course of itraconazole; however, she is being monitored for potential recurrence of infection and the need for resumption of itraconazole. FIGURE Lesions occurring on two patients with first reported U.S. cases of tinea caused by Trichophyton indotineae, on patient A’s neck, abdomen, and buttocks (A–C)* and on patient B’s thighs † (D) — New York City, December 2021–March 2023 Photos/Lu Yin (A–C) and Vignesh Ramachandran (D). Used with patients’ permission. * At initial dermatology evaluation, patient A had large, annular, scaly, and pruritic erythematous plaques of the neck, abdomen, groin, and buttocks. † At initial dermatology evaluation, patient B had widespread, discrete, scaly, annular, pruritic plaques affecting the thighs and buttocks. The figure includes four photographs of lesions occurring on the neck, abdomen, and thigh areas of two patients in New York City, caused by the first reported U.S. cases of tinea due to Trichophyton indotineae infection during December 2021–March 2023. Patient B, a woman aged 47 years with no major medical conditions, developed a widespread, pruritic eruption in summer 2022 while in Bangladesh. There, she received treatment with topical antifungal and steroid combination creams and noted that several family members were experiencing similar eruptions. After returning to the United States, she visited an emergency department three times during autumn 2022. She was prescribed hydrocortisone 2.5% ointment and diphenhydramine (visit 1), clotrimazole cream (visit 2), and terbinafine cream (visit 3) with no improvement. In December 2022, she was evaluated by dermatologists who noted widespread, discrete, scaly, annular, pruritic plaques affecting the thighs and buttocks (Figure). She received a 4-week course of oral terbinafine, but her symptoms did not improve. She then received a 4-week course of griseofulvin therapy, resulting in approximately 80% improvement. Itraconazole therapy is being considered pending further evaluation given the recent confirmation of suspected T. indotineae infection. Her son and husband, who live in the same house and report similar eruptions, are currently undergoing evaluation. The cases in these two patients highlight several important points. Patient A had no recent international travel history, suggesting potential local U.S. transmission of T. indotineae. Health care providers should consider T. indotineae infection in patients with widespread tinea, particularly when eruptions do not improve with first-line topical antifungal agents or oral terbinafine. Culture-based identification techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentographytes or T. interdigitale; correct identification requires genomic sequencing. Health care providers who suspect T. indotineae infection should contact their state or local public health department for assistance with testing,** which is available at certain public health laboratories and specialized academic and commercial laboratories. Successful treatment using oral itraconazole, a triazole antifungal, has been documented. However, providers should be aware of challenges with itraconazole absorption, †† which can lead to variable serum drug concentrations; itraconazole's interactions with other drugs; the need for up to 12 weeks of therapy ( 3 ); and the documented emergence of triazole resistance ( 4 , 5 ). Antimicrobial stewardship efforts are essential to minimize the misuse and overuse of prescribed and over-the-counter antifungal drugs and corticosteroids. In addition, health care providers can educate patients about strategies to prevent the spread of the dermatophytes that cause tinea. §§ Finally, public health surveillance efforts and increased testing could help detect and monitor the spread of T. indotineae.
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            The Growing Problem of Antifungal Resistance in Onychomycosis and Other Superficial Mycoses.

            Superficial mycoses are becoming increasingly resistant to current antifungal medications. As alternative therapeutic options are limited, the increasing frequency of reports of antifungal resistance is alarming. This epidemic parallels the rise of antibiotic resistance; however, the significance of this problem has yet to gain global attention. Here, we discuss the reports of antifungal resistance from around the world, present our own experience with treatment-resistant infections, and examine alternative treatment strategies. The majority of reports of recalcitrant infections indicate terbinafine resistance as the causative factor. Single-point mutations in the squalene oxidase gene is the most reported mechanism of resistance to terbinafine. Mixed infections of dermatophytes with non-dermatophyte molds and/or yeasts are becoming more prevalent and contributing to the resistant nature of these infections. The key to selecting an effective antifungal therapy for a recalcitrant infection is identification of the infectious organisms(s) and testing susceptibility of the organism(s) to antifungal drugs. Combination and sequential therapy regimens are options, but both require active monitoring for hepatic and renal function, drug interactions, and other adverse effects. Selected topical antifungals with a wide spectrum of activity may also be considerations in some clinical presentations. Innovative treatment regimens and novel therapeutics are needed to overcome the rising epidemic of antifungal resistance.
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              The emergence of Trichophyton indotineae: Implications for clinical practice.

              Emergence and increase of terbinafine-resistant dermatophytosis led to the identification of Trichophyton mentagrophytes internal transcriber space (ITS) genotype VIII in 2017, later renamed as Trichophyton indotineae and classified as a separate species in 2020. With its suspected origin in South Asia, this novel strain has emerged in Bahrain, Canada, Denmark, Finland, France, Germany, India, Iran, Japan, Russia, and Switzerland, with its spread attributed primarily to travel and migration. Diagnosis using routine mycology laboratory techniques is unable to distinguish T. indotineae from T. mentagrophytes and T. interdigitale; specific identification requires genomic sequencing to identify unique, specific markers. One speculated reason for this recent outbreak is the unrestricted use of topical steroid creams and antifungal agents. Patients with extensive tinea corporis and cruris due to T. indotineae present with inflammatory red plaques in multiple body sites. The majority of these infections prove to be resistant to conventional antifungals, including allylamines and azoles (itraconazole and fluconazole), thus emphasizing the need for antifungal susceptibility testing before treatment initiation and for reassessing in nonresponsive patients. Molecular studies have identified several point mutations in the ERG1 (terbinafine resistance) and ERG11 (azole resistance) genes, which need to be analyzed further. Use of relatively new agents, such as voriconazole and luliconazole, as well as device modalities and combination therapy, could be investigated for recalcitrant T. indotineae infections.
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                Author and article information

                Journal
                MMWR Morb Mortal Wkly Rep
                MMWR Morb Mortal Wkly Rep
                WR
                Morbidity and Mortality Weekly Report
                Centers for Disease Control and Prevention
                0149-2195
                1545-861X
                11 January 2024
                11 January 2024
                : 73
                : 1
                : 1-5
                Affiliations
                Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC; Israel Englander Department of Dermatology, Weill Cornell Medicine, New York, New York.
                Author notes
                Corresponding author: Jeremy A. W. Gold, jgold@ 123456cdc.gov .
                Article
                mm7301a1
                10.15585/mmwr.mm7301a1
                10794060
                38206854
                b4dd6bfd-9589-458d-b9d7-875cfcc0fc94

                All material in the MMWR Series is in the public domain and may be used and reprinted without permission; citation as to source, however, is appreciated.

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