A Brazilian Inter-Hospital Candidemia Outbreak Caused by Fluconazole-Resistant Candida parapsilosis in the COVID-19 Era

Abstract

Horizontal transmission of fluconazole-resistant Candida parapsilosis (FRCP) through healthcare workers’ hands has contributed to the occurrence of candidemia outbreaks worldwide. Since the first COVID-19 case in Brazil was detected in early 2020, hospitals have reinforced hand hygiene and disinfection practices to minimize SARS-CoV-2 contamination. However, a Brazilian cardiology center, which shares ICU patients with a cancer center under a FRCP outbreak since 2019, reported an increased FRCP candidemia incidence in May 2020. Therefore, the purpose of this study was to investigate an inter-hospital candidemia outbreak caused by FRCP isolates during the first year of the COVID-19 pandemic in Brazil. C. parapsilosis bloodstream isolates obtained from the cancer (n = 35) and cardiology (n = 30) centers in 2020 were submitted to microsatellite genotyping and fluconazole susceptibility testing. The ERG11 gene of all isolates from the cardiology center was sequenced and compared to the corresponding sequences of the FRCP genotype responsible for the cancer center outbreak in 2019. Unprecedentedly, most of the FRCP isolates from the cardiology center presented the same genetic profile and Erg11-Y132F mutation detected in the strain that has been causing the persistent outbreak in the cancer center, highlighting the uninterrupted horizontal transmission of clonal isolates in our hospitals during the COVID-19 pandemic.

Global emergence of resistance to fluconazole and voriconazole in Candida parapsilosis in tertiary hospitals in Spain during the COVID-19 pandemic

“…Recent emergence of FNS isolates in C. parapsilosis has been described in other countries in the literature [11-20], so our data supports that the increase of azole resistance in C. parapsilosis might be a global problem. In this study, the majority of resistant isolates harbored the Y132F mutation, which has been largely associated in the literature with the appearance of clonal outbreaks.…”

“…Acquired resistance to fluconazole in C. parapsilosis is a rare phenomenon, being less than 5% of isolates in different epidemiological studies [2,[7][8][9][10]. In recent years, however, a steady increase of resistance has been observed worldwide, mostly in the context of nosocomial outbreaks [11][12][13][14][15][16][17][18][19][20]. In many cases, these outbreaks are monoclonal, and are associated to mutations in ERG11 (mainly with the Y132F mutation), overexpression of efflux pumps (as Mdr1 and Cdr1) and mutations in MRR1, which encodes a transcription factor that regulates the expression of some efflux pumps [11-13, 16, 18, 21, 22].…”

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

“…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.…”

CRISPR-Cas9 editing induces Loss of Heterozygosity in the pathogenic yeast Candida parapsilosis

“…Unlike Candida albicans, C. parapsilosis has been associated with nosocomial infection outbreaks worldwide (3)(4)(5)(6). Severe C. parapsilosis infections are a concern in intensive care units and neonatal intensive care units, where they are associated with neonatal mortality (7,8).…”

“…The opportunistic fungal pathogen Candida parapsilosis is a member of the CUG-Ser1 clade (1), and the second or third most frequently isolated Candida species (2). Unlike Candida albicans, C. parapsilosis has been associated with nosocomial infection outbreaks worldwide (3-6). Severe C. parapsilosis infections are a concern in intensive care units and neonatal intensive care units, where they are associated with neonatal mortality (7, 8).…”