Journal Article

Antifungal Therapeutic Failure - Need for a More Comprehensive Review

Sonthalia, Sidharth

2019

Overview

Pending a formal consensus on the clinical terminology encompassed under AFTF, terms such as recurrence, relapse, recalcitrance, and chronic persistence seem to represent its varied clinical presentations.[2] Authors used a term, “clinical resistance,” which in my opinion is different from AFTF (that should include facets of only clinical non- or suboptimal-response) and includes the dichotomy between the in vivo and in vitro response to a particular drug/therapy. The rationale of this distinction is the prevalent confusion amongst dermatologists, and the need for according weighted emphasis to contributing factors other than AFR, to harness the epidemic of AFTF in toto ·It is regrettable that ciclopirox (CPX), one of the most promising solutions to the emerging antifungal resistance, was not even mentioned; despite its approval for superficial mycoses having been given in 1985 and 1996 by the Drug Controller General of India and US-FDA, respectively. Not a single case of clinical or in vivo resistance to CPX has been reported despite more than three decades of its frequent use for tinea and mucocutaneous yeast infections globally.[3] Further, in vitro susceptibility to CPX of multiple strains of yeasts have been reported to be better than various azoles including itraconazole and ketoconazole.[4] The reported penetrance of topical CPX into the hair follicles and sebaceous glands [3] also offsets the problem of treatment failures potentially attributable to the recently elucidated dermatophytic invasion of vellus hair in tinea corporis.[5] Finally, laboratory and clinical studies reporting development of resistance and cross resistance of dermatophytes to ergosterol synthesis inhibitors (ESI) specifically itraconazole, terbinafine, and amorolfine following repeated subcultures in sub-inhibitory drug concentrations (in vitro) and prolonged clinical therapy with azoles (in vivo) respectively, failed to show emergence of resistance to CPX.[3] The two most important factors plausibly contributing to the above phenomenon include: 1) unique ESI-independent antifungal mechanism of CPX that involves inhibition of the trivalent metal ion-dependent enzymes leading to accumulation of intracellular peroxides, and 2) irreversible binding to intracellular structures rescuing CPX from drug efflux mechanisms.[3] The potent anti-inflammatory activity of CPX (equivalent to 2.5% hydrocortisone) is a boon, as cognizance of this fact can prevent prescription of steroid-based combination topicals that are often prescribed by clinicians to provide early relief to the patient; albeit at the cost of increasing the likelihood of therapeutic failure and the abuse of and dependence on such topicals by the patients.[3] ·The role of agricultural fungicides contributing to primary azole resistance was mentioned, but the Indian scenario was missed out.

• Publisher: Wolters Kluwer - Medknow,Medknow Publications and Media Pvt. Ltd,Medknow Publications & Media Pvt. Ltd,Wolters Kluwer Medknow Publications
• Subject: Antifungal agents / CORRESPONDENCE / Failure / Fungicides / Health aspects / Microbial drug resistance / Patient compliance / Pesticides