scholarly journals Molecular Epidemiology and Antifungal Susceptibility of Trichophyton Isolates in Greece: Emergence of Terbinafine-Resistant Trichophytonmentagrophytes Type VIII Locally and Globally

2021 ◽  
Vol 7 (6) ◽  
pp. 419
Author(s):  
Maria Siopi ◽  
Ioanna Efstathiou ◽  
Konstantinos Theodoropoulos ◽  
Spyros Pournaras ◽  
Joseph Meletiadis
Keyword(s):  
Molecular Epidemiology ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Cross Resistance ◽  
Squalene Epoxidase ◽  
In Vitro Susceptibility ◽  
Type Viii ◽  
In Vitro Antifungal Susceptibility ◽  
Resistance Rates

Trichophyton isolates with reduced susceptibility to antifungals are now increasingly reported worldwide. We therefore studied the molecular epidemiology and the in vitro antifungal susceptibility patterns of Greek Trichophyton isolates over the last 10 years with the newly released EUCAST reference method for dermatophytes. Literature was reviewed to assess the global burden of antifungal resistance in Trichophyton spp. The in vitro susceptibility of 112 Trichophyton spp. molecularly identified clinical isolates (70 T. rubrum, 24 T. mentagrophytes, 12 T. interdigitale and 6 T. tonsurans) was tested against terbinafine, itraconazole, voriconazole and amorolfine (EUCAST E.DEF 11.0). Isolates were genotyped based on the internal transcribed spacer (ITS) sequences and the target gene squalene epoxidase (SQLE) was sequenced for isolates with reduced susceptibility to terbinafine. All T. rubrum, T. interdigitale and T. tonsurans isolates were classified as wild-type (WT) to all antifungals, whereas 9/24 (37.5%) T. mentagrophytes strains displayed elevated terbinafine MICs (0.25–8 mg/L) but not to azoles and amorolfine. All T. interdigitale isolates belonged to ITS Type II, while T. mentagrophytes isolates belonged to ITS Type III* (n = 11), VIII (n = 9) and VII (n = 4). All non-WT T. mentagrophytes isolates belonged to Indian Genotype VIII and harbored Leu393Ser (n = 5) and Phe397Leu (n = 4) SQLE mutations. Terbinafine resistance rates ranged globally from 0–44% for T. rubrum and 0–76% for T. interdigitale/T. mentagrophytes with strong endemicity. High incidence (37.5%) of terbinafine non-WT T. mentagrophytes isolates (all belonging to ITS Type VIII) without cross-resistance to other antifungals was found for the first time in Greece. This finding must alarm for susceptibility testing of dermatophytes at a local scale particularly in non-responding dermatophytoses.

Molecular epidemiology and in vitro antifungal susceptibility ofTrichophyton schoenleinii,agent of tinea capitis favosa

Mycoses ◽  
2019 ◽  
Vol 62 (5) ◽  
pp. 466-474
Author(s):  
Yangmin Gao ◽  
Ping Zhan ◽  
Ferry Hagen ◽  
Steph B. J. Menken ◽  
Jiufeng Sun ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Tinea Capitis ◽  
Antifungal Susceptibility ◽  
In Vitro Antifungal Susceptibility

scholarly journals In Vitro Antifungal Susceptibility Testing of Candida Isolates with the EUCAST Methodology, a New Method for ECOFF Determination

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
J. Meletiadis ◽  
I. Curfs-Breuker ◽  
J. F. Meis ◽  
J. W. Mouton
Keyword(s):  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Second Derivative ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
In Vitro Antifungal Susceptibility ◽  
Resistance Rates

ABSTRACT The in vitro susceptibilities of 1,099 molecularly identified clinical Candida isolates against 8 antifungal drugs were determined using the EUCAST microdilution method. A new simple, objective, and mathematically solid method for determining epidemiological cutoff values (ECOFFs) was developed by derivatizing the MIC distribution and determining the derivatized ECOFF (dECOFF) as the highest MIC with the maximum second derivative. The dECOFFs were similar (95% agreement within 1 dilution) to the EUCAST ECOFFs. Overall, low non-wild-type/resistance rates were found. The highest rates were found for azoles with C. parapsilosis (2.7 to 9.8%), C. albicans (7%), and C. glabrata (1.7 to 2.3%) and for echinocandins with C. krusei (3.3%), C. albicans (1%), and C. tropicalis (1.7%).

scholarly journals Isolation of Candida africana in oral candidiasis: First report among cancer patients in Iran

2020 ◽  
Author(s):  
Ensieh Lotfali ◽  
Masoud Mardani ◽  
Sara Abolghasemi ◽  
David Darvishnia ◽  
Mohammad Mahdi Rabiei ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Amphotericin B ◽  
Oral Candidiasis ◽  
Antifungal Susceptibility ◽  
Empirical Therapy ◽  
Antifungal Prophylaxis ◽  
In Vitro Susceptibility ◽  
Molecular Tests ◽  
In Vitro Antifungal Susceptibility

Background and Purpose: Oropharyngeal candidiasis (OPC) is a fungal infection of the oral cavity caused by the members of C. albicans complex. Although C. africana, as a part of the complex, is considered to be mostly responsible for the development of vulvovaginal candidiasis, it may be associated with a wider clinical spectrum. Case report: This report described two cases diagnosed with oral candidiasis during the receipt of treatment for malignancies. Conventional and molecular tests were performed on the samples collected from the patients’ oral cavities. The test results revealed C. africana as the causative agent of oral candidiasis. Furthermore, in vitro antifungal susceptibility test indicated the full susceptibility of all C. africana isolates to caspofungin. However, the data were also suggestive of the resistance against fluconazole and amphotericin B. Caspofungin was used as the main antifungal agent for the treatment of oral candidiasis, resulting in the improvement of thrush in patients. The resistance of C. africana to fluconazole and amphotericin B suggests the necessity of performing in vitro susceptibility testing on the isolates for the selection of appropriate antifungal agents. Conclusion: As the findings indicated, the achievement of knowledge regarding C. africana as an emerging non-albicans Candida species and its antifungal susceptibility profile is crucial to select antifungal prophylaxis and empirical therapy for oral candidiasis in cancer patients undergoing chemotherapy.

scholarly journals Antifungal Susceptibility Testing of Dermatophytes: Establishing a Medium for Inducing Conidial Growth and Evaluation of Susceptibility of Clinical Isolates

2000 ◽  
Vol 38 (1) ◽  
pp. 341-344
Author(s):  
C. J. Jessup ◽  
J. Warner ◽  
N. Isham ◽  
I. Hasan ◽  
M. A. Ghannoum
Keyword(s):  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Antifungal Susceptibility Testing ◽  
Optimal Conditions ◽  
In Vitro Susceptibility ◽  
Conidial Formation ◽  
The Mean ◽  
Optimal Medium

ABSTRACT A standardized reference method for dermatophyte in vitro susceptibility testing is lacking. In a previous study, Norris et al. (H. A. Norris, B. E. Elewski, and M. A. Ghannoum, J. Am. Acad. Dermatol. 40(6, part 2):S9–S13) established the optimal medium and other growth variables. However, the earlier study did not address two issues: (i) selection of an optimal medium for conidial formation by dermatophytes and (ii) validation of the method with a large number of dermatophytes. The present study addresses these two points. To select which agar medium best supported conidial growth, representative isolates of dermatophytes were grown on different agars. Preliminary experiments showed that only oatmeal cereal agar supported the production of conidia by Trichophyton rubrum . We tested the abilities of 251 T. rubrum isolates to form conidia using three different cereal agars and potato dextrose agar. Overall, oatmeal cereal and rice agar media were comparable in their abilities to support T. rubrum conidial growth. Next, we used the oatmeal cereal agar for conidial formation along with the optimal conditions for dermatophyte susceptibility testing proposed by Norris et al. and determined the antifungal susceptibilities of 217 dermatophytes to fluconazole, griseofulvin, itraconazole, and terbinafine. Relative to the other agents tested, terbinafine possessed the highest antifungal activity against all of the dermatophytes. The mean ± standard error of the mean MICs of fluconazole, itraconazole, terbinafine, and griseofulvin were 2.07 ± 0.29, 0.13 ± 0.01, 0.002 ± 0.0003, and 0.71 ± 0.05 μg/ml, respectively. This study is the first step in the identification of optimal conditions that could be used for the standardization of the antifungal susceptibility testing method for dermatophytes. Inter- and intralaboratory agreement as well as clinical correlations need to be established.

scholarly journals 146. antifungal Susceptibility Patterns of candida Parapsilosis Bloodstream Isolates in the US, 2008–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S203-S203
Author(s):  
Brenda L Tesini ◽  
Meghan Lyman ◽  
Brendan R Jackson ◽  
Anita Gellert ◽  
William Schaffner ◽  
...  
Keyword(s):  
Candida Species ◽  
Regional Variation ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Emerging Infections ◽  
In Vitro Susceptibility ◽  
Fluconazole Resistance ◽  
The Us ◽  
Susceptibility Patterns

Abstract Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (< 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

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
Keyword(s):  
Gene Mutation ◽  
Susceptibility Testing ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Antifungal Susceptibility Testing ◽  
Squalene Epoxidase ◽  
Exclusion Criteria ◽  
Huge Variation

<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.

Use of spectrophotometric reading for in vitro antifungal susceptibility testing ofAspergillusspp.

1999 ◽  
Vol 45 (10) ◽  
pp. 871-874 ◽  
Author(s):  
Eric Dannaoui ◽  
Florence Persat ◽  
Marie-France Monier ◽  
Elisabeth Borel ◽  
Marie-Antoinette Piens ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Antifungal Susceptibility Testing ◽  
Aspergillus Species ◽  
National Committee ◽  
Broth Microdilution Method

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.

scholarly journals Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis

2000 ◽  
Vol 44 (8) ◽  
pp. 2081-2085 ◽  
Author(s):  
Beth A. Arthington-Skaggs ◽  
David W. Warnock ◽  
Christine J. Morrison
Keyword(s):  
Murine Model ◽  
Invasive Candidiasis ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Resistant Isolate ◽  
National Committee ◽  
Ergosterol Content ◽  
In Vitro Antifungal Susceptibility

ABSTRACT MIC end point determination for the most commonly prescribed azole antifungal drug, fluconazole, can be complicated by “trailing” growth of the organism during susceptibility testing by the National Committee for Clinical Laboratory Standards approved M27-A broth macrodilution method and its modified broth microdilution format. To address this problem, we previously developed the sterol quantitation method (SQM) for in vitro determination of fluconazole susceptibility, which measures cellular ergosterol content rather than growth inhibition after exposure to fluconazole. To determine if SQM MICs of fluconazole correlated better with in vivo outcome than M27-A MICs, we used a murine model of invasive candidiasis and analyzed the capacity of fluconazole to treat infections caused by C. albicansisolates which were trailers (M27-A MICs at 24 and 48 h, ≤1.0 and ≥64 μg/ml, respectively; SQM MIC, ≤1.0 μg/ml), as well as those which were fluconazole sensitive (M27-A and SQM MIC, ≤1.0 μg/ml) and fluconazole resistant (M27-A MIC, ≥64 μg/ml; SQM MIC, 54 μg/ml). Compared with the untreated controls, fluconazole therapy increased the survival of mice infected with a sensitive isolate and both trailing isolates but did not increase the survival of mice infected with a resistant isolate. These results indicate that the SQM is more predictive of in vivo outcome than the M27-A method for isolates that give unclear MIC end points due to trailing growth in fluconazole.

Sign in / Sign up

Export Citation Format

Share Document