Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution

Díaz-García, Judith; Gómez, Ana; Alcalá, Luís; Reigadas, Elena; Sánchez‐Carrillo, Carlos; Balzola, Ana Perez-Ayala; Pedrosa, Elia Gómez-García de la; González-Romo, Fernando; Merino-Amador, Paloma; Cuétara, María Soledad; García-Esteban, Coral; Quiles-Melero, Inmaculada; Zurita, Nelly Daniela; Muñoz-Algarra, María; Sánchez-Romero, Isabel; Durán-Valle, María Teresa; Sánchez-García, Aída; Alcoceba, Eva; Muñoz, Patricia; Escribano, Pilar; Guinea, Jesús

doi:10.1128/aac.00710-22

Cited by 26 publications

(46 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both C. parapsilosis isolates were resistant to FLU ( Table 2 ) and harbored the Y132F and R398I mutations due to the following nucleotide substitutions A395T and G1193T, respectively. This observation is in good agreement with other studies [ 29 , 30 , 31 ].…”

Section: Resultssupporting

confidence: 94%

“…C. parapsilosis isolates share a common antimicrobial profile in which the high MIC to fluconazole (FLU > 256 mg/L) stands out. Azole resistance in C. parapsilosis is well documented, being at the molecular level associated with two multidrug transporters (Cdr1 and Mdr1) and an enzyme involved in ergosterol biosynthesis (lanosterol 14α-demethylase coded by the ERG11 gene) [ 27 , 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, this is the first report in Portugal of the detection of these two mutations linked to azole resistance, although previously described for C. parapsilosis responsible for BSI in other countries [ 30 , 31 ]. Moreover, a recent study monitoring the antifungal resistance in C. parapsilosis isolates at Madrid metropolitan area hospitals for the last three years proved that isolates used for sequencing the ERG11 gene mainly harbored the Y132F Erg11p amino acid substitution [ 29 ]. Results obtained from qPCR analysis of both C. parapsilosis isolates suggested that regulation of tested genes does not play an important role in FLU resistance, and probably, found mutations in the ERG11 gene (Y132F and R398I) were responsible for resistance to FLU.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

et al. 2022

View full text Add to dashboard Cite

Biofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility of central venous catheters (CVCs) and hemoculture (HC) isolates was evaluated, including whole genome sequencing (WGS) resistome analysis and evaluation of gene expression to obtain insight into their AMR determinants. Crystal violet assay was used to assess dual biofilm biomass and microscopy was used to elucidate a microorganism’s distribution within biofilms assembled on different materials. Bacteria were multidrug-resistant including resistance to colistin and beta-lactams, likely linked to the mcr-9-like phosphoethanolamine transferase and to an ACT family cephalosporin-hydrolyzing class C beta-lactamase, respectively. The R398I and Y132F mutations in the ERG11 gene and its differential expression might account for C. parapsilosis resistance to fluconazole. The phenotype of dual biofilms assembled on glass, polystyrene and polyurethane depends on the material and how biofilms were initiated by one or both pathogens. Biofilms assembled on polyurethane were denser and richer in the extracellular polymeric matrix, and microorganisms were differently distributed on the inner/outer surface of the CVC.

show abstract

Section: Resultssupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In particular, genotype 10 has disseminated through different hospitals and Cataluña, genotype 96 was first found in Madrid and Burgos, and genotype 67 was found in the Balearic Islands and Cantabria. Similar findings have recently been described from hospitals in Madrid [ 32 ]. When analyzing the sample isolation dates, our data suggest that the major clone that circulated in hospitals in Madrid disseminated to Burgos Hospital.…”

Section: Resultssupporting

confidence: 91%

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic

Trevijano-Contador

Torres-Cano

Carballo-González

et al. 2022

Open Forum Infectious Diseases

Self Cite

View full text Add to dashboard Cite

Background Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole non-susceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last two years at the Spanish Mycology Reference Laboratory. Methods Yeast were identified by molecular biology and antifungal susceptibility testing was performed using EUCAST protocol. ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results We examined the susceptibility profile of 1,315 C. parapsilosis isolates available at our Reference Laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole and voriconazole has increased in at least eight different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia, and clone 96 in Castilla-Leon and Madrid, wereas clone 67 was found in two geographically unrelated regions, Cantabria and Balearic Islands). Conclusions Our data suggests that concurrently with the COVID-19 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

show abstract

“…Some fluconazole-resistant C. parapsilosis isolates presented a wild-type ERG11 gene sequence (Arastehfar et al, 2020a, Arastehfar et al, 2020b, thus suggesting alternative ( Grossman et al, 2015;Souza et al, 2015;Asadzadeh et al, 2017;Magobo et al, 2017;Choi et al, 2018;Thomaz et al, 2018;Alobaid and Khan, 2019;Singh et al, 2019, Arastehfar et al, 2020a, Arastehfar et al, 2020b, Castanheira et al, 2020Magobo et al, 2020;Martini et al, 2020;Arastehfar et al, 2021;Corzo-Leon et al, 2021;Demirci-Duarte et al, 2021;Fekkar et al, 2021;Thomaz et al, 2021;Alcoceba et al, 2022, Diaz-Garcia et al, 2022a, Hare et al, 2022Thomaz et al, 2022;Zaragoza et al, 2022) K143R** R S ( Singh et al, 2019, Arastehfar et al, 2020a, Castanheira et al, 2020 G458S*** R R o r I ( Arastehfar et al, 2020a, Demirci-Duarte et al, 2021 (Grossman et al, 2015). **The K143R substitution may be present in combination with Y132F substitutions.…”

Section: Molecular Basis Of Fluconazole Resistance In C Parapsilosismentioning

confidence: 99%

Fluconazole-resistant Candida parapsilosis: A new emerging threat in the fungi arena

Escribano

Guinea

2022

Front. Fungal Biol.

Self Cite

View full text Add to dashboard Cite

Candida parapsilosis is a leading cause of invasive candidiasis in southern Europe, Latin America and Asia. C. parapsilosis has been mostly considered susceptible to triazoles, but fluconazole resistance is on the rise in some countries. The main mechanism related to fluconazole resistance is the presence of ERG11p substitutions, dominated by the Y132F amino acid substitution. Isolates harbouring this substitution mimic C. auris given that they may cause hospital outbreaks, become endemic, and emerge simultaneously in distant areas around the world. At the moment, Spain is experiencing a brusque emergence of fluconazole resistance in C. parapsilosis; isolates harbouring the Y132F substitution were detected for the first time in 2019. A recent study on Candida spp isolates from blood cultures collected in 16 hospitals located in the Madrid metropolitan area (2019 to 2021) reported that fluconazole resistance in C. parapsilosis reached as high as 13.6%. Resistance rates rose significantly during those three years: 3.8% in 2019, 5.7% in 2020, and 29.1% in 2021; resistant isolates harboured either the dominant Y132F substitution (a single clone found in four hospitals) or G458S (another clone found in a fifth hospital). The COVID-19 pandemic may have increased the number of candidaemia cases. The reason for such an increase might be a consequence of uncontrolled intra-hospital patient-to-patient transmission in some hospitals, as an increase not only in C. parapsilosis candidaemia episodes but also in the spread of clonal fluconazole-resistant isolates might have occurred in other hospitals during the pandemic period. Patients affected with fluconazole-resistant C. parapsilosis harbouring the Y132F substitution presented a mortality rate ranging from 9% to 78%, were mainly admitted to intensive care wards but did not have differential risk factors compared to those infected by susceptible isolates. With scarce exceptions, few patients (≤20%) infected with fluconazole-resistant isolates had previously received fluconazole, thus supporting the fact that, although fluconazole might have been a key factor to promote resistance, the main driver promoting the spread of fluconazole-resistant isolates was patient-to-patient transmission.

show abstract

Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution

Abstract: We have been monitoring the antifungal resistance in Candida parapsilosis isolates collected from inpatients at Madrid metropolitan area hospitals for the last 3 years. The study aimed to elucidate the presence of fluconazole-resistant C. parapsilosis genotypes in Madrid.

Cited by 26 publications

References 30 publications

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic

Fluconazole-resistant Candida parapsilosis: A new emerging threat in the fungi arena

Contact Info

Product

Resources

About