Rational for drug dosimetry and duration of terbinafine in the context of recalcitrant dermatophytosis: Is 500 mg better than 250 mg OD or BD?

Sardana, Kabir; Gupta, Aastha

doi:10.4103/ijd.ijd_435_17

Cited by 14 publications

(9 citation statements)

References 18 publications

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“…in recent reports (8)(9)(10)(11)(12). Consequently, the use of high TRB dosages, in treatment of dermatophytoses, is becoming common (6,13). However, it is important to emphasize that clinical breakpoints have not been defined for TRB in dermatophyt-oses and that the in vitro data cannot be directly applied to clinical situations.…”

mentioning

confidence: 99%

Correlation ofIn VitroSusceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris

Khurana

Masih

Chowdhary

et al. 2018

Antimicrob Agents Chemother

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102

108

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Recalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase (SQLE) gene mutations conferring resistance inTrichophytonspp. have been recently documented. However, studies correlating laboratory data with clinical response to TRB in tinea corporis/cruris are lacking. For this study, we investigated the clinicomycological profile of 85 tinea corporis/cruris patients and performed antifungal susceptibility testing by CLSI microbroth dilution and SQLE mutation analysis of the isolates obtained and correlated these with the responses to TRB. Patients confirmed by potassium hydroxide (KOH) mounting of skin scrapings were started on TRB at 250 mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks, the same dose was continued (group 1). If response was <50%, the dose was increased to 250 mg twice a day (BD) (group 2). If the response still remained below 50% after 3 weeks of BD, the patients were treated with itraconazole (ITR; group 3). Overall, skin scrapings from 64 (75.3%) patients yielded growth on culture. Strikingly, all isolates were confirmed to beTrichophyton interdigitaleisolates by internal transcribed spacer (ITS) sequencing. Thirty-nine (61%) of the isolates had TRB MICs of ≥1 µg/ml. Complete follow-up data were available for 30 culture-positive patients. A highly significant difference in modal MICs to TRB among the three treatment response groups was noted (P = 0.009). Interestingly, 8 of the 9 patients in group 3 harbored isolates exhibiting elevated TRB MICs (8 to 32 µg/ml) and SQLE mutations. The odds of achieving cure with TRB MIC < 1 µg/ml strains were 2.5 times the odds of achieving cure with the strain exhibiting MIC ≥1 µg/ml.

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mentioning

confidence: 99%

Correlation ofIn VitroSusceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris

Khurana

Masih

Chowdhary

et al. 2018

Antimicrob Agents Chemother

Self Cite

102

108

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“…Following topical administration to normal skin, cream‐terbinafine formulations were found to attain concentrations ranging from 746 to 949 ng/cm 2 , as described elsewhere 18–20 . In 7‐day application, high terbinafine concentration levels were found in stratum corneum (2–5 μg/cm 2 ), and a concentration of the drug higher than the minimal inhibitory concentration for most dermatophytes was still found 48 days after the last day of medication 21 . Even after such a long period of application, the terbinafine concentrations were significantly lower than that found for luliconazole after 24 h. Further, after oral treatment with terbinafine, 36% of dermatophytes in nail scrapings had survived, although the concentration of the drug in the nails was 10‐fold greater than the minimal fungicidal concentration 22 .…”

Section: Introductionmentioning

confidence: 78%

“…[18][19][20] In 7-day application, high terbinafine concentration levels were found in stratum corneum (2-5 μg/cm 2 ), and a concentration of the drug higher than the minimal inhibitory concentration for most dermatophytes was still found 48 days after the last day of medication. 21 Even after such a long period of application, the terbinafine concentrations were significantly lower than that found for luliconazole after 24 h. Further, after oral treatment with terbinafine, 36% of dermatophytes in nail scrapings had survived, although the concentration of the drug in the nails was 10-fold greater than the minimal fungicidal concentration. 22 In the case of luliconazole, approximately 5% of dermatophytes in skin scales survived despite topical application of 1% cream, which achieved a concentration of approximately 8000-fold greater than the minimal fungicidal concentration.…”

mentioning

confidence: 85%

Therapeutic efficacy of topically used luliconazole vs. terbinafine 1% creams

Gnat

Dyląg

Łagowski

et al. 2021

Mycoses

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Dermatophytoses are the most common agents of superficial fungal infections in the world, affecting a substantial part of the human population. 1,2 The increased frequency of fungal infectious diseases recorded in the last several years can be attributed to environmental factors, lifestyle and adaptation of fungi to the environment. For example, improper hygiene, occlusive footwear, socioeconomic conditions, new types of professions, animal breeding in flats, frequent trips to warm climate regions, civilisation diseases such as diabetes mellitus, increasing resistance of pathogens to antifungal substances and even climate change have been attributed to this notable increase in the prevalence of fungal infections. [3][4][5][6][7][8] In recent years, the introduction of new antifungal agents has provided major advances in the therapy of dermatophytosis. 3,8,9 One of such drugs, luliconazole, was first approved for therapy in Japan in 2005.Later, it was approved in India and the United States in 2010 and 2013, respectively. 10,11 This drug has an imidazole moiety introduced into the ketene dithioacetate structure, which effectively interferes with ergosterol biosynthesis by inhibition of sterol 14 α-demethylase. 11,12

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“…A divided dose of 250 mg twice daily is preferred over 500 mg once daily since single dose defies the basic principles of pharmacokinetics/pharmacodynamics of the drug. 66…”

Section: Terbinafinementioning

confidence: 99%

The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options

Verma¹,

Panda²,

Nenoff³

et al. 2021

IJDVL

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One of the canonical features of the current outbreak of dermatophytosis in India is its unresponsiveness to treatment in majority of cases. Though there appears to be discordance between in vivo and in vitro resistance, demonstration of in vitro resistance of dermatophytes to antifungals by antifungal susceptibility testing is essential as it may help in appropriate management. The practical problem in the interpretation of antifungal susceptibility testing is the absence of clinical breakpoints and epidemiologic cutoff values. In their absence, evaluation of the upper limit of a minimal inhibitory concentration of wild type isolates may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility. In the current scenario, most of the cases are unresponsive to standard dosages and duration of treatment recommended until now. This has resulted in many ex-cathedra modalities of treatment that are being pursued without any evidence. There is an urgent need to carry out methodical research to develop an evidence base to formulate a rational management approach in the current scenario.

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Rational for drug dosimetry and duration of terbinafine in the context of recalcitrant dermatophytosis: Is 500 mg better than 250 mg OD or BD?

Cited by 14 publications

References 18 publications

Correlation ofIn VitroSusceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris

Correlation ofIn VitroSusceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris

Therapeutic efficacy of topically used luliconazole vs. terbinafine 1% creams

The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options

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