How to interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST)

Arendrup, Maiken Cavling; Friberg, Nathalie; Mareș, Mihai; Kahlmeter, Gunnar; Meletiadis, Joseph; Guinea, Jesús; Andersen, Cecilie Torp; Arıkan-Akdağlı, Sevtap; Barchiesi, Francesco; Chryssanthou, Erja; Hamal, Petr; Järv, H.; Климко, Н Н; Kurzai, Oliver; Lagrou, Katrien; Lass‐Flörl, Cornelia; Matos, Tadeja; Müehlethaler, Konrad; Rogers, Thomas R.; Velegraki, Aristea; Arıkan, Sevtap

doi:10.1016/j.cmi.2020.06.007

Cited by 143 publications

(141 citation statements)

References 36 publications

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“…The A. nomiae isolate in our patient was resistant to AMB (S ≤ / > R = 1/1) according to the latest drug resistance criteria (Arendrup et al, 2020). This resistance permitted angioinvasion by the fungus, which led to treatment failure.…”

Section: Discussionmentioning

confidence: 76%

“…The MIC endpoints for itraconazole, voriconazole, posaconazole, and AMB were determined using a reading mirror as the lowest concentration of the drug that prevented any recognizable growth (100% inhibition). The MIC results were interpreted according to the revised clinical breakpoints v. 10.0 of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), who defines new criteria for resistance to AMB (S ≤ / > R = 1/1) (Arendrup et al, 2020). The other revised breakpoints include itraconazole (ATU = 2) and isavuconazole against A. flavus (S usvuszolevucoATU = 2); isavuconazole (S ≤ / > R = 1/2, ATU = 2), itraconazole [S conazole (S oATU = 2)], posaconazole (ATU = 0.25), and voriconazole [S conazole (S iATU = 2)] against A. fumigatus, itraconazole (S conazoletracoATU = 2), and voriconazole [S conazole (S nATU = 2)] against Aspergillus nidulans, AMB against Aspergillus niger (S rgerst n B) against itraconazole [S conazole (S gATU = 2)], and posaconazole (ATU = 0.25) against Aspergillus terreus.…”

Section: Antifungal Susceptibility Testingmentioning

confidence: 99%

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Fatal Rhinofacial Mycosis Due to Aspergillus nomiae: Case Report and Review of Published Literature

Zhou

Houbraken

et al. 2020

Front. Microbiol.

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BackgroundA 73-year-old female suffering from acute myeloid leukemia presented with progressive rhinofacial mycosis. Suspecting it to be mucormycosis, the antifungal amphotericin B (AMB) was administered empirically, but the patient did not respond as planned. The fungus was then isolated from the biopsied tissue and morphologically identified as a species of Aspergillus. Necrosis progressed and she died of cerebral hemorrhage. Since Aspergillus flavus is susceptible to AMB, and several other Aspergillus species can be misidentified as A. flavus, the observed resistance necessitated a re-examination of the fungal isolate.MethodsThe fungal strain was re-isolated and re-examined morphologically. Additionally, genomic DNA was extracted from the fungus and sequences were obtained from three genomic regions [the rDNA internal transcribed spacer (ITS) region, and portions of the β-tubulin and calmodulin genes] to more accurately identify this Aspergillus strain. Its antifungal susceptibility was assessed using multiple compounds and our findings were compared with literature data.ResultsThe fungal culture again yielded an Aspergillus isolate morphologically identical to A. flavus. Molecular analyses, however, revealed the strain to be A. nomiae, a close relative of A. flavus in section Flavi, and it exhibited resistance to AMB. Reviewing the literature, only five other cases of A. nomiae infection in humans have been reported worldwide.Conclusion and Clinical ImportanceThe rhinofacial mycosis of the patient was actually due to A. nomiae. The initial misidentification of the fungus, coupled with its resistance to AMB, could be the reason treatment did not help the patient. We postulate that clinical A. nomiae infections may be underreported and that accurate and speedy pathogen identification is important so that an effective antifungal regimen can be administered.

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Section: Discussionmentioning

confidence: 76%

Section: Antifungal Susceptibility Testingmentioning

confidence: 99%

Fatal Rhinofacial Mycosis Due to Aspergillus nomiae: Case Report and Review of Published Literature

Zhou

Houbraken

et al. 2020

Front. Microbiol.

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“…The remaining ten voriconazole‐resistant isolates showed MIC values of 2 mg/L, falling within the Area of Technical Uncertainty (AUT), previously named ‘intermediate category’; however they can't be considered wild‐type (WT) according to EUCAST Epidemiological Cut‐OFF values (WT ECOFF ≤ 1 mg/L). 22 …”

Section: Resultsmentioning

confidence: 99%

Azole resistance in Aspergillus isolates by different types of patients and correlation with environment ‐ An Italian prospective multicentre study (ARiA study)

Prigitano

Esposto

Grancini

et al. 2021

Mycoses

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Background A wide range of frequency of azole‐resistance in A fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options. Objectives Estimate the prevalence of azole‐resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment. Methods Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole‐resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole‐resistant isolates from previous Italian studies. Results 425 Aspergillus isolates from 367 patients were analysed. The azole‐resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole‐resistant species were identified: A thermomutatus and A lentulus. The predominant resistance mechanism was TR34/L98H. No correlation between the clinical resistant strains and environmental isolates from patients’ home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole‐resistant genotypes starting from a founder azole‐resistant genotype. Conclusions This study confirms the trend of azole‐resistance rate in Italy, showing a geographical difference. Data reinforce the importance of surveillance programmes to monitor the local epidemiological situation.

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“…Using the former CB for micafungin of C. albicans, a frequent misclassification for borderline resistant strains was noted. Arendrup et al recently reported ten isolates of C. albicans with a micafungin MIC of 0.032 mg/L and an anidulafungin MIC of up to 0.032 mg/L without any target mutations in the hot spot regions [22], thus underlining that the former CB misclassified the genotypical wildtype strains as resistant. We observed the same phenomenon in an even higher number of C. albicans isolates (n = 86).…”

Section: Discussionmentioning

confidence: 99%

Do Candida albicans Isolates with Borderline Resistant Micafungin MICs Always Harbor FKS1 Hot Spot Mutations?

Spettel

Sonia

Kriz

et al. 2021

JoF

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Antifungal susceptibility testing is important in guiding patient therapy due to an increasing number of resistant Candida isolates. In the clinical strain collection of the Austrian resistance report (AURES), a high number of micafungin-resistant C. albicans isolates (18.2% 49/269) was detected in seven different centres in Austria from 2011–2016. Most of these isolates showed a micafungin MIC value that was just above the clinical breakpoint (CB) established by EUCAST (0.016 mg/L). The aim of this study was to analyse whether C. albicans strains showing a micafungin MIC value of 1–2 dilutions above the CB (0.032 mg/L and 0.064 mg/L) are associated with mutations in FKS1 hotspot (HS) regions. 115 C. albicans candidemia strains showing a micafungin MIC one or two dilutions above the EUCAST CB (0.032 mg/L and 0.064 mg/L) were categorized as borderline resistant and screened for mutations in FKS1 HS1, HS2, and HS3 regions, which are known locations for the development of echinocandin resistance. For this purpose, we implemented targeted resequencing utilizing a next generation sequencing technology. No missense mutations could be detected in FKS1 HS1, HS2, and HS3 in any of the 115 isolates, which indicated that resistance conferred by alteration of FKS1 seems unlikely.

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How to interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST)

Cited by 143 publications

References 36 publications

Fatal Rhinofacial Mycosis Due to Aspergillus nomiae: Case Report and Review of Published Literature

Fatal Rhinofacial Mycosis Due to Aspergillus nomiae: Case Report and Review of Published Literature

Azole resistance in Aspergillus isolates by different types of patients and correlation with environment ‐ An Italian prospective multicentre study (ARiA study)

Do Candida albicans Isolates with Borderline Resistant Micafungin MICs Always Harbor FKS1 Hot Spot Mutations?

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