New Insights into the Cyp51 Contribution to Azole Resistance in
            <i>Aspergillus</i>
            Section
            <i>Nigri</i>

Pérez-Cantero, Alba; López-Fernández, Loida; Guarro, Josep; Capilla, Javier

doi:10.1128/aac.00543-19

Cited by 11 publications

(9 citation statements)

References 53 publications

(69 reference statements)

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“…A. tubingensis, A. welwitschiae and A. luchuensis/awamori in section Nigri also responded to high MICs of ITR (>16 μg ml −1 ). The considerable prevalence of A. tubingensis and some other cryptic species with different antifungal susceptibility patterns in clinical samples, which was observed here and in other studies from different countries [39][40][41], emphasizes the importance of the correct identification of Aspergillus species.…”

Section: Discussionsupporting

confidence: 79%

Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri

Nargesi

Jafarzadeh

Najafzadeh

et al. 2022

Journal of Medical Microbiology

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Introduction. Aspergillus sections Flavi and Nigri comprise clinically relevant and cryptic species that differ significantly in drug susceptibility, meaning that effective treatment depends on correct species identification. Hypothesis/Gap Statement. There are no comprehensive data for molecular identification and antifungal susceptibility testing (AFST) of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri as the main agents of invasive and non-invasive aspergillosis in Iran. We aimed to perform molecular identification and AFST of 213 clinical Aspergillus isolates belonging to sections Flavi and Nigri. Molecular identification of isolates was performed using sequencing of the β-tubulin gene and in vitro AFST was conducted according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 guidelines. Results. The most common isolates in sections Flavi and Nigri were Aspergillus flavus (110/113, 97.3 %) and Aspergillus tubingensis (49/100, 49.0 %), respectively. A total of 62/213 (29.1 %) isolates belonging to cryptic species were identified; among them, A. tubingensis was the most prevalent (49/62, 79.0%). Aspergillus flavus and A. niger isolates that responded to the minimum inhibitory concentrations (MICs) of itraconazole above the epidemiological cutoff values were the most frequently detected: 8/110 (7.3 %) and 3/41 (7.3 %), respectively. In section Flavi, Aspergillus alliaceus responded to amphotericin B at a high MIC (>16 µg mL−1) and in section Nigri, one of the three Aspergillus luchuensis/awamori isolates responded to itraconazole at an MIC >16 µg ml−1. Interestingly, for all Aspergillus welwitschiae isolates, the MIC50 and MIC90 of itraconazole were both 16 µg ml−1. Conclusion. A considerable presence of A. flavus and A. niger isolates showing non-wild-type responses to azoles in clinical cases of aspergillosis indicates the importance of classifying clinical Aspergillus isolates at the species level and performing antifungal susceptibility testing on the isolates, which would ensure appropriate treatment.

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Section: Discussionsupporting

confidence: 79%

Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri

Nargesi

Jafarzadeh

Najafzadeh

et al. 2022

Journal of Medical Microbiology

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“…For A. fumigatus , A. flavus , A. niger and A. terreus , they are in general susceptible to amphotericin B, itraconazole and voriconazole. Although azole resistance has been reported for these Aspergillus species, it is still relatively uncommon 27‐30 . However, in this study, we observed that a number of the rare/cryptic Aspergillus species isolates do not possess similar antifungal susceptibility patterns as the classical pathogenic Aspergillus species.…”

Section: Discussioncontrasting

confidence: 53%

Rare/cryptic Aspergillus species infections and importance of antifungal susceptibility testing

Tsang

Tang

Yé

et al. 2020

Mycoses

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Summary Background The number of patients infected with Aspergillus rose dramatically in recent years. However, studies on the clinical spectrum and antifungal susceptibilities of non‐classical (non‐fumigatus, non‐flavus, non‐niger and non‐terreus) pathogenic Aspergillus species are very limited. Objectives We examined the clinical spectrum and antifungal susceptibilities of 34 non‐duplicated, non‐classical Aspergillus isolates collected from Hong Kong, Shenzhen and Shanghai. Methods The Aspergillus isolates were identified by internal transcribed spacer, partial BenA and partial CaM sequencing and phylogenetic analyses. Susceptibility testing against eight antifungals was performed following the European Committee for Antimicrobial Susceptibility Testing's methodology. Results The 34 Aspergillus isolates were identified as 14 different rare/cryptic species of four sections (Flavi [n = 8], Nidulantes [n = 8], Nigri [n = 17] and Restricti [n = 1]). Except for one patient whose clinical history could not be retrieved, 72.7% of the remaining patients had underlying conditions predisposing them to Aspergillus infections. The most common diseases were pulmonary infections (n = 15), followed by skin/nail infections (n = 6), chronic otitis externa and/or media (n = 5), wound infections (n = 2) and mastoiditis/radionecrosis (n = 1), while three were colonisations. Five patients succumbed due to the infections during the admission, and another two died 5 years later because of chronic pulmonary aspergillosis. Antifungal susceptibility testing showed that they possessed different susceptibility profiles compared to the classical Aspergillus species. The majority of isolates characterised were sensitive or wild‐type to amphotericin B. The minimum effective concentrations for all the three echinocandins were also low. Conclusion Susceptibility testing should be performed for infections due to these rare/cryptic Aspergillus species to guide proper patient management.

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“…In agreement with previous studies [ 3 , 34 ], Aspergillus alliaceus ( flavus complex) and Aspergillus tubingensis ( niger complex) show a variable susceptibility against azoles; A. alliaceus also yielding elevated MICs against amphotericin B. Ibrexafungerp was mostly inactive against A. alliaceus , as 75% (by EUCAST) and 40% (by CLSI) of the total number of isolates tested showed MECs > 2 mg/L. When tested in vitro against A. flavus strains in previous studies, this new drug did not display a homogenous effectiveness, being reported as active in some studies, with MEC values ranging from 0.06 mg/L to 0.25 mg/L [ 14 , 16 ], but as inactive in another (MEC range 2–16 mg/L) [ 15 ].…”

Section: Resultssupporting

confidence: 94%

In Vitro Activity of Ibrexafungerp against a Collection of Clinical Isolates of Aspergillus, Including Cryptic Species and Cyp51A Mutants, Using EUCAST and CLSI Methodologies

Rivero-Menéndez

Soto-Debrán

Cuenca‐Estrella

et al. 2021

JoF

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Ibrexafungerp is a new orally-available 1,3-β-D-glucan synthesis inhibitor in clinical development. Its in vitro activity and that of amphotericin B, voriconazole, and micafungin were evaluated against a collection of 168 clinical isolates of Aspergillus spp., including azole–susceptible and azole–resistant (Cyp51A mutants) Aspergillus fumigatus sensu stricto (s.s.) and cryptic species of Aspergillus belonging to six species complexes showing different patterns of antifungal resistance, using EUCAST and CLSI antifungal susceptibility testing reference methods. Ibrexafungerp displayed low geometric means of minimal effective concentrations (MECs) against A. fumigatus s.s. strains, both azole susceptible (0.040 mg/L by EUCAST and CLSI versus 1.231 mg/L and 0.660 mg/L for voriconazole, respectively) and azole resistant (0.092 mg/L and 0.056 mg/L, EUCAST and CLSI, while those for voriconazole were 2.144 mg/L and 2.000 mg/L). Ibrexafungerp was active against most of the cryptic species of Aspergillus tested, yielding MEC values only comparable to those of micafungin. Nevertheless, this new compound exhibited a moderate activity against A. ustus complex species, MECs ≥ 0.5 mg/L against Aspergillus insuetus and Aspergillus keveii strains, and was inactive against the Aspergillus alliaceus isolates tested (MEC90s ≥ 16 mg/L). All in all, ibrexafungerp shows encouraging in vitro results against cryptic species of Aspergillus and azole–susceptible and azole resistant strains of A. fumigatus, some of which are difficult to treat using the available therapeutic options.

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New Insights into the Cyp51 Contribution to Azole Resistance in Aspergillus Section Nigri

Cited by 11 publications

References 53 publications

Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri

Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri

Rare/cryptic Aspergillus species infections and importance of antifungal susceptibility testing

In Vitro Activity of Ibrexafungerp against a Collection of Clinical Isolates of Aspergillus, Including Cryptic Species and Cyp51A Mutants, Using EUCAST and CLSI Methodologies

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