scholarly journals The Emerging Terbinafine-Resistant Trichophyton Epidemic: What Is the Role of Antifungal Susceptibility Testing?

Dermatology ◽  
2021 ◽  
pp. 1-20
Author(s):  
Julia J. Shen ◽  
Maiken C. Arendrup ◽  
Shyam Verma ◽  
Ditte Marie L. Saunte

<b><i>Background:</i></b> Dermatophytosis is commonly encountered in the dermatological clinics. The main aetiological agents in dermatophytosis of skin and nails in humans are <i>Trichophyton</i> (<i>T</i>.) <i>rubrum</i>, <i>T. mentagrophytes</i> and <i>T. interdigitale</i> (former <i>T. mentagrophytes-</i>complex). Terbinafine therapy is usually effective in eradicating infections due to these species by inhibiting their squalene epoxidase (SQLE) enzyme, but increasing numbers of clinically resistant cases and mutations in the SQLE gene have been documented recently. Resistance to antimycotics is phenotypically determined by antifungal susceptibility testing (AFST). However, AFST is not routinely performed for dermatophytes and no breakpoints classifying isolates as susceptible or resistant are available, making it difficult to interpret the clinical impact of a minimal inhibitory concentration (MIC). <b><i>Summary:</i></b> PubMed was systematically searched for terbinafine susceptibility testing of dermatophytes on October 20, 2020, by two individual researchers. The inclusion criteria were <i>in vitro</i> terbinafine susceptibility testing of <i>Trichophyton (T.) rubrum</i>, <i>T. mentagrophytes</i> and <i>T. interdigitale</i> with the broth microdilution technique. The exclusion criteria were non-English written papers. Outcomes were reported as MIC range, geometric mean, modal MIC and MIC<sub>50</sub> and MIC<sub>90</sub> in which 50 or 90% of isolates were inhibited, respectively. The reported MICs ranged from &#x3c;0.001 to &#x3e;64 mg/L. The huge variation in MIC is partly explained by the heterogeneity of the <i>Trichophyton</i> isolates, where some originated from routine specimens (wild types) whereas others came from non-responding patients with a known SQLE gene mutation. Another reason for the great variation in MIC is the use of different AFST methods where MIC values are not directly comparable. High MICs were reported particularly in isolates with SQLE gene mutation. The following SQLE alterations were reported: F397L, L393F, L393S, H440Y, F393I, F393V, F415I, F415S, F415V, S443P, A448T, L335F/A448T, S395P/A448T, L393S/A448T, Q408L/A448T, F397L/A448T, I121M/V237I and H440Y/F484Y in terbinafine-resistant isolates.

2020 ◽  
Author(s):  
Jie Liu ◽  
Lanting Liu ◽  
Xiaoyun Liu ◽  
Bo Yu ◽  
Xiaoping Hu

Abstract The research on antifungal resistance in dermatophytoses lags behind that on systemic mycose. Lack of datas of antifungal susceptibility testing in dermatophytoses is one reasion. 121 clinical dermatophytes isolates were tested against 6 azole antifungal agents according to the Clinical and Laboratory Standards Institute (CLSI) method. Geometric mean MIC of all isolates were in increasing order: isavuconazole (GM 0.06 mg/L), posaconazole (GM 0.10 mg/L), itraconazole (GM 0.22 mg/L), voriconazole (GM 0.32 mg/L), ketoconazole (GM 0.40 mg/L), fluconazole (GM 10.18 mg/L).


2001 ◽  
Vol 45 (6) ◽  
pp. 1828-1835 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Bartlett ◽  
V. Chaturvedi ◽  
M. Ghannoum ◽  
K. C. Hazen ◽  
...  

ABSTRACT The most important role of susceptibility testing is to identify potentially resistant isolates for the agent being evaluated. Standard testing guidelines recently have been proposed for antifungal susceptibility testing of filamentous fungi (molds). This collaborative (eight centers) study evaluated further newly proposed guidelines (NCCLS, proposed standard M38-P, 1998) and other testing conditions for antifungal susceptibility testing of Aspergillus spp. to itraconazole and three new triazoles, posaconazole (SCH56592), ravuconazole (BMS-207147), and voriconazole. MICs of itraconazole, posaconazole, ravuconazole, and voriconazole for 15 selected isolates of three species of Aspergillus (A. fumigatus, A. flavus, and A. terreus) with well documented in vitro, clinical, or animal data were determined in each center by using four medium formulations (standard RPMI-1640 [RPMI], RPMI with 2% dextrose, antibiotic medium 3 [M3], and M3 with 2% dextrose) and two criteria of MIC determination (complete [MIC-0s] and prominent [MIC-2s] growth inhibition) at 24, 48, and 72 h. The highest reproducibility (92 to 99%) was seen with the standard RPMI and M3 media. Moreover, the distinction between itraconazole-resistant (MICs of >8 μg/ml for clinically resistant strains) and -susceptible (MICs of 0.03 to 1 μg/ml) isolates, as well as between a voriconazole-resistant laboratory mutant and other isolates (voriconazole MICs of 2 to >8 versus 0.12 to 2 μg/ml), was more consistently evident with the standard RPMI medium and when MIC-0s were determined at 48 h. These results provide further refinement of the testing guidelines for susceptibility testing ofAspergillus spp. and warrant consideration for inclusion in the future NCCLS document M38-A.


1999 ◽  
Vol 45 (10) ◽  
pp. 871-874 ◽  
Author(s):  
Eric Dannaoui ◽  
Florence Persat ◽  
Marie-France Monier ◽  
Elisabeth Borel ◽  
Marie-Antoinette Piens ◽  
...  

A comparative study of visual and spectrophotometric MIC endpoint determinations for antifungal susceptibility testing of Aspergillus species was performed. A broth microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS) was used for susceptibility testing of 180 clinical isolates of Aspergillus species against amphotericin B and itraconazole. MICs were determined visually and spectrophotometrically at 490 nm after 24, 48, and 72h of incubation, and MIC pairs were compared. The agreement between the two methods was 99% for amphotericin B and ranged from 95 to 98% for itraconazole. It is concluded that spectrophotometric MIC endpoint determination is a valuable alternative to the visual reference method for susceptibility testing of Aspergillus species.Key words: antifungal, susceptibility testing, Aspergillus, spectrophotometric reading.


2021 ◽  
Vol 17 ◽  
Author(s):  
Zarifeh Adampour ◽  
Malihe Hasanzadeh ◽  
Hossein Zarrinfar ◽  
Maryam Nakhaei ◽  
Monika Novak Babič

Introduction: Endometrial cancer is one of the most common malignancies of the female genital tract, which can be serious or life-threatening. Microbial infections can be one of the underlying causes of this type of cancer. Case Presentation: The present study describes the isolation of Pichia fermentans (Candida firmentaria var. firmentaria) from the vaginal secretions of a 61-year-old woman affected by endometrial cancer. She reported abdominal pain and vaginal discharge for 3 months, and had a history of diabetes, hypertension, Deep Vein Thrombosis (DVT), and Acute Myeloid Leukemia (AML). The isolated yeast was identified based on nuclear ribosomal internal transcribed spacer (ITS1-ITS2 rDNA) sequence analysis. The in vitro antifungal susceptibility testing showed a higher effect for ketoconazole against P. fermentans than fluconazole, itraconazole and voriconazole. Conclusion: Correct differentiation between P. fermentans and other yeast should be considered. The in vitro antifungal susceptibility testing is recommended for rare yeast, and will help the physicians in providing the best treatment.


2001 ◽  
Vol 45 (9) ◽  
pp. 2475-2479 ◽  
Author(s):  
Gordon Ramage ◽  
Kacy Vande Walle ◽  
Brian L. Wickes ◽  
José L. López-Ribot

ABSTRACT Candida albicans is implicated in many biomaterial-related infections. Typically, these infections are associated with biofilm formation. Cells in biofilms display phenotypic traits that are dramatically different from those of their free-floating planktonic counterparts and are notoriously resistant to antimicrobial agents. Consequently, biofilm-related infections are inherently difficult to treat and to fully eradicate with normal treatment regimens. Here, we report a rapid and highly reproducible microtiter-based colorimetric assay for the susceptibility testing of fungal biofilms, based on the measurement of metabolic activities of the sessile cells by using a formazan salt reduction assay. The assay was used for in vitro antifungal susceptibility testing of severalC. albicans strains grown as biofilms against amphotericin B and fluconazole and the increased resistance of C. albicans biofilms against these antifungal agents was demonstrated. Because of its simplicity, compatibility with a widely available 96-well microplate platform, high throughput, and automation potential, we believe this assay represents a promising tool for the standardization of in vitro antifungal susceptibility testing of fungal biofilms.


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