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1.
Expert Rev Clin Pharmacol ; 10(2): 225-237, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27868472

ABSTRACT

INTRODUCTION: Dermatophytosis is generally defined as an infection of the hair, nails, or glabrous skin. These infections are caused by the keratinophilic fungi Trichophyton spp., Microsporum spp., and Epidermophyton, which have been recovered from both symptomatic and asymptomatic individuals. Although dermatophytosis is generally not a life-threatening condition, these types of infections are among the most common infections worldwide, and their incidence has continued to increase consistently in recent years. Area covered: This article provides an overview of the general characteristics of dermatophytes, including their taxonomy and epidemiology, as well as the different clinical forms and laboratory diagnostics of dermatophytosis. We further classify the topical and systemic antifungal compounds currently used to treat dermatophyte infections. Expert commentary: Antifungal therapy is a central component of patient management for dermatophytosis, and depending on the strategy chosen, topical and/or systemic drugs can be used. However, for effective treatment, it is important to correctly determine the causal agents at the species level, which will enable administration of suitable therapeutics and initiation of appropriate management strategies.


Subject(s)
Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Dermatomycoses/drug therapy , Administration, Topical , Humans
2.
Antimicrob Agents Chemother ; 60(1): 387-92, 2016 01.
Article in English | MEDLINE | ID: mdl-26525787

ABSTRACT

We employed an endpoint genotyping method to update the prevalence rate of positivity for the TR34/L98H mutation (a 34-bp tandem repeat mutation in the promoter region of the cyp51A gene in combination with a substitution at codon L98) and the TR46/Y121F/T289A mutation (a 46-bp tandem repeat mutation in the promoter region of the cyp51A gene in combination with substitutions at codons Y121 and T289) among clinical Aspergillus fumigatus isolates obtained from different regions of Iran over a recent 5-year period (2010 to 2014). The antifungal activities of itraconazole, voriconazole, and posaconazole against 172 clinical A. fumigatus isolates were investigated using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. For the isolates with an azole resistance phenotype, the cyp51A gene and its promoter were amplified and sequenced. In addition, using a LightCycler 480 real-time PCR system, a novel endpoint genotyping analysis method targeting single-nucleotide polymorphisms was evaluated to detect the L98H and Y121F mutations in the cyp51A gene of all isolates. Of the 172 A. fumigatus isolates tested, the MIC values of itraconazole (≥16 mg/liter) and voriconazole (>4 mg/liter) were high for 6 (3.5%). Quantitative analysis of single-nucleotide polymorphisms showed the TR34/L98H mutation in the cyp51A genes of six isolates. No isolates harboring the TR46/Y121F/T289A mutation were detected. DNA sequencing of the cyp51A gene confirmed the results of the novel endpoint genotyping method. By microsatellite typing, all of the azole-resistant isolates had genotypes different from those previously recovered from Iran and from the Dutch TR34/L98H controls. In conclusion, there was not a significant increase in the prevalence of azole-resistant A. fumigatus isolates harboring the TR34/L98H resistance mechanism among isolates recovered over a recent 5-year period (2010 to 2014) in Iran. A quantitative assay detecting a single-nucleotide polymorphism in the cyp51A gene of A. fumigatus is a reliable tool for the rapid screening and monitoring of TR34/L98H- and TR46/Y121F/T289A-positive isolates and can easily be incorporated into clinical mycology algorithms.


Subject(s)
Antifungal Agents/therapeutic use , Aspergillus fumigatus/genetics , Cytochrome P-450 Enzyme System/genetics , Drug Resistance, Fungal/genetics , Fungal Proteins/genetics , Polymorphism, Single Nucleotide , Aspergillosis/drug therapy , Aspergillosis/epidemiology , Aspergillosis/microbiology , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/enzymology , Aspergillus fumigatus/isolation & purification , Cytochrome P-450 Enzyme System/metabolism , DNA, Fungal/genetics , Fungal Proteins/metabolism , Gene Expression , Humans , Iran/epidemiology , Itraconazole/therapeutic use , Microbial Sensitivity Tests , Microsatellite Repeats , Mycological Typing Techniques , Promoter Regions, Genetic , Retrospective Studies , Sequence Analysis, DNA , Triazoles/therapeutic use , Voriconazole/therapeutic use
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