Abstract
Recently, clinical failure and relapses have been observed in patients treated with antifungals. Drug resistance has become an important problem leading to significant negative social, psychological, and occupational health effects and quality of life. Early recognition and treatment is essential to reduce morbidity and possibility of transmission. The increased use, inappropriate prescribing and over the counter sale of antifungal agents has also added in the development of resistance to these drugs. The main biochemical and molecular mechanisms that contribute to antifungal resistance include reduced uptake of the drug, an active transport out of the cell or modified drug metabolic degradation of the cell, changes in the interaction of the drug to the target site or other enzymes involved in the process by point mutations, overexpression of the target molecule, overproduction or mutation of the target enzyme, amplification and gene conversion (recombination), and increased cellular efflux and occurrence of biofilm. Although, there is considerable knowledge concerning the biochemical, genetic and clinical aspects of resistance to antifungal agents, expansion of our understanding of the mechanisms by which antifungal resistance emerges and spreads, quicker methods for the determination of resistance, targetting efflux pumps, especially ATP binding cassette (ABC) transporters and heat shock protein 90, new drug delivery systems, optimizing therapy according to pharmacokinetic and pharmacodynamic characteristics, new classes of antifungal drugs that are active against azole-resistant isolates, and use of combinations of antifungal drugs or use of adjunctive immunostimulatory therapy and other modalities of treatment will clearly be important for future treatment strategies and in preventing development of resistance.
Highlights
Superficial dermatophytoses affecting skin, hair and nail are among the most common public health problem in hot and humid climate of tropical countries like India
Antifungal-drug resistance is usually quantified using the minimum inhibitory concentration (MIC), in which growth in the presence of a range of drug concentrations is measured over a defined time period according to a standard protocol [41].The lowest drug concentration that results in a significant reduction of growth is called the MIC
Antifungal drug resistance is clearly becoming a common problem in patients and is inevitable due to wide availability and use of these agents
Summary
Superficial dermatophytoses affecting skin, hair and nail are among the most common public health problem in hot and humid climate of tropical countries like India. World Health Organization estimates dermatophytes affect about 25% of the world population [3]. The most common dermatophytes that cause cutaneous mycoses are Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Trichophyton tonsurans [6]. Epidemiological studies on occurrence of dermatophytes have shown that T. rubrum is present in 80% of cases and T. mentagrophytes in 20% [8]. T. rubrum is the most prevalent dermatophyte and affects children and adults in about 33.2% of the cases identified, followed by T. mentagrophytes in 6.3% cases [9]. In a study conducted over a period of three years, Bright et al reported the isolation of dermatophytes in 12.99% of cases of onychomycosis, and T. rubrum isolated in 9.04% of patients and T. tonsurans and T. mentagrophytes 2.54% and 1.41% of subjects, respectively [10]. The prevalence of drug resistance in fungi is below that observed in bacteria, mycologists believe that selective pressure will, over time, lead to more widespread resistance [11]
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