Hospital outbreak of fluconazole-resistant Candida parapsilosis: arguments for clonal transmission and long-term persistence

Abstract

The worldwide emergence of multidrug-resistant pathogenic fungi is a threat to human health. At this very moment, an emergence of Candida parapsilosis isolates harbouring a resistance to fluconazole, one of the most popular antifungal drugs, is being described in several countries. We seek to better understanding the epidemiology, pathogenicity and transmission of resistant Candida parapsilosis Faced with an outbreak of invasive infections due to resistant isolates of C. parapsilosis, we performed a 7-year retrospective and prospective analysis of 283 C. parapsilosis isolates collected in 240 patients, among who 111 had invasive candidiasis. Study included review of hospital records, genotyping analysis and susceptibility testing that allow determining the type and outcome of infections, as well as the spatial and temporal spread of clusters. Overall the incidence of azole resistance was 7.5%. Genotyping analysis unveiled several previously undetected outbreaks and clonal spread of susceptible and resistant isolates over a long period of time. In comparison with susceptible isolates, resistant ones have a more restricted genetic diversity and seem to be more likely to spread and more frequently associated with invasive infections. In intensive care units, patients with invasive infections due to resistant isolates had poorer outcome (overall mortality at day 30 of 40%; 4/10) than susceptible ones (overall mortality at day 30 of 26.5%; 9/34). Our results suggest that the propensity of C. parapsilosis to spread on an epidemic fashion is underestimated, which warrants reinforced control and epidemiological survey of this species.

FIG 1

UPGMA (unweighted pair group method with arithmetic mean) dendrogram of 93 Candida parapsilosis isolates typed by microsatellite approach. Fluconazole-resistant isolates (n = 26) are highlighted in yellow. Isolates from a single intensive care unit are in red. R1 and R2 represent 2 clusters of fluconazole-resistant isolates responsible for 2 outbreaks in 4 and 10 patients, respectively. S1 to S3 represent clusters of susceptible isolates.

FIG 2

Spatial and temporal circulation of Candida parapsilosis fluconazole-resistant isolates belonging to a single cluster (R1) among patients with invasive candidiasis hosted in different buildings of a single hospital between 2012 and 2017.