Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge

Abstract

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.

Increasing Incidence and Shifting Epidemiology of Candidemia in Greece: Results from the First Nationwide 10-Year Survey

“…These factors may be associated with the high rate of FLC-resistant C. parapsilosis SC bloodstream isolates reported in the present study. Worryingly, a significant increase in their incidence rate was identified over time (from 0% in 2009 to 32% in 2018, p < 0.0001), as previously described [74,87], whereas FLC-VRC cross-resistance occurred in a high proportion of such isolates, being consistent with previous findings [54,74,85,92,98]. Notably, a trend of higher mortality rates in candidemic patients infected with FLC-resistant C. parapsilosis SC than in those with FLC-susceptible (42-50% versus 16-26%, respectively) has been described [87,92].…”

“…While the phenomenon had appeared to be restricted to certain geographic regions, an ever-growing number of FLC-resistant clinical isolates have been reported worldwide from Brazil [57,83,84], France [85], India [86], Korea [87,88], Kuwait [32], North America [82], and South Africa [56,89], whilst the problem is already broadly disseminated in Italy [48,82,90] and Turkey [91][92][93]. FLC resistance C. parapsilosis SC has been well associated with selective drug pressure attributable to the extensive use of FLC as prophylaxis and treatment or even to exposure to systemic antimicrobials [94,95] with subsequent patient-to-patient spread in an epidemic way with clonal transmission and establishment of persistent resistant isolates within the hospital environment [83][84][85]92]. In the present study, FLC-resistant C. parapsilosis SC strains were found in all medical units of hospitals geographically distributed all over the country.…”

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

“…While R398I has been considered only a compensatory Erg11 alteration, Y132F is the main one detected in FRCP isolates and seems to confer potential for dissemination [35]. Moreover, it has been associated with high mortality rates [13,18]. Thus, the inter-hospital spread of FRCP clonal isolates with Erg11-Y132F during the COVID-19 pandemic makes this pathogen an even more evident emerging public health problem.…”

“…In contrast to the prior colonization-dependent vertical transmission of C. albicans, the horizontal transmission of C. parapsilosis is supported by its propensity to colonize the hands of healthcare workers, to form biofilm on CVC, and to grow rapidly in TPN, making it a Candida species of high concern in ICUs [7,8]. Even more worrisome are the increasingly frequent candidemia outbreaks caused by C. parapsilosis resistant to fluconazole (FLC) [9][10][11][12][13], the main antifungal drug used for candidemia treatment in developing countries [5].…”

Participation of the ABC Transporter CDR1 in Azole Resistance of Candida lusitaniae

“…In C. albicans , TAC1 regulates the ABC transporter genes CDR1 and CDR2 , while MRR1 regulates the major facilitator MDR1 [ 10 , 18 , 27 , 28 ]. In the past few years, TAC1 and MRR1 homologs have been described in several other fungal pathogens including Candida parapsilosis , Candida tropicalis and C. auris [ 29 , 30 , 31 ]. A TAC1 homolog exists in C. lusitaniae (CLUG_02369) with about 55% similarity to the C. albicans TAC1 .…”