Exposure of Cryptococcus neoformans to Seven Commonly Used Agricultural Azole Fungicides Induces Resistance to Fluconazole as Well as Cross-Resistance to Voriconazole, Posaconazole, Itraconazole and Isavuconazole

Drakulovski, Pascal; Krasteva, Donika; Bellet, Virginie; Randazzo, Sylvie; Roger, Frédéric; Pottier, Cyrille; Bertout, Sébastien

doi:10.3390/pathogens12050662

Cited by 5 publications

(1 citation statement)

References 73 publications

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“…The use of fluconazole as primary antifungal prophylaxis in the prevention of cryptococcal meningitis further drives the uncontrolled use of this azole, which could also potentially lead to the development of antifungal resistance ( 13 ). Recently, the exposure to azole pesticides used in agriculture was as well reported to be responsible for the appearance of resistance to medical azoles in C. neoformans , as has been well documented for other environmental pathogenic fungi, such as A. fumigatus ( 56 ).…”

Section: Discussionmentioning

confidence: 91%

Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase

et al. 2023

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Section: Discussionmentioning

confidence: 91%

Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase

et al. 2023

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Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex from China, including the diploid VNIII isolates from HIV-infected patients in Chongqing region

Zhang,

Wang,

Hong

et al. 2023

Medical Mycology

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Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information about the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines. Among 171 isolates, six sequence types (STs) were identified, including the dominant ST5 isolates, the newly reported ST15, and four diploid VNIII isolates (ST632/ST636). Moreover, a total of 1019 CNSC isolates with STs and HIV-status information were collected and analyzed from Mainland China in the present study. A minimum spanning analysis grouped these 1019 isolates into three main subgroups, which were dominated by the ST5 clonal complex (CC5), followed by the ST31 clonal complex (CC31) and ST93 clonal complex (CC93). The trend of resistance or decreasing susceptibility of clinical CNSC isolates to azole agents within HIV-infected patients from the Chongqing region is increasing, especially resistance to fluconazole.

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Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011–2021

Ordaya,

Abu Saleh,

Vergidis

et al. 2024

Mycoses

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BackgroundThere are no established clinical breakpoints for antifungal agents against Cryptococcus species; however, epidemiological cut‐off values can help distinguish wild‐type (WT) isolates without any acquired resistance from non‐WT strains, which may harbour resistance mechanisms.Patients/MethodsWe describe the trends of antifungal MICs and percentages of WT C. neoformans species complex (CNSC) isolates processed in our reference laboratory from November 2011 to June 2021. There were only nine isolates in 2011, thus, we included them in the year 2012 for data analysis. Clinical data is also described when available.ResultsWe identified 632 CNSC, the majority collected from blood (n = 301), cerebrospinal fluid (n = 230), and respiratory (n = 71) sources. The overall percentage of WT isolates for amphotericin B (AMB), 5‐flucytosine, and fluconazole was 77%, 98%, and 91%, respectively. We noticed a statistically significant change in the percentage of AMB WT isolates over the years, with 98% of isolates being WT in 2012 compared to 79% in 2021 (p < .01). A similar change was not observed for other antifungal agents. Clinical data was available for 36 patients, primarily non‐HIV immunocompromised patients with disseminated cryptococcosis. There were no statistically significant differences in the clinical characteristics and outcomes between patients with WT (58.3%) versus non‐WT (41.7%) isolates, but we noticed higher mortality in patients infected with an AMB non‐WT CNSC isolate.ConclusionsWe observed an increase in the percentage of AMB non‐WT CNSC isolates in the past decade. The clinical implications of this finding warrant further evaluation in larger studies.

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Exposure of Cryptococcus neoformans to Seven Commonly Used Agricultural Azole Fungicides Induces Resistance to Fluconazole as Well as Cross-Resistance to Voriconazole, Posaconazole, Itraconazole and Isavuconazole

Cited by 5 publications

References 73 publications

Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase

Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase

Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex from China, including the diploid VNIII isolates from HIV-infected patients in Chongqing region

Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011–2021

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