An Azole-Resistant Candida parapsilosis Outbreak: Clonal Persistence in the Intensive Care Unit of a Brazilian Teaching Hospital

Abstract

The incidence of candidemia by the Candida parapsilosis complex has increased considerably in recent decades, frequently related to use of indwelling intravascular catheters. The ability of this pathogen to colonize healthcare workers (HCW)' hands, and to form biofilm on medical devices has been associated with the occurrence of nosocomial outbreaks and high mortality rates. Fluconazole has been the leading antifungal drug for the treatment of invasive candidiasis in developing countries. However, azole-resistant C. parapsilosis isolates are emerging worldwide, including in Brazil. Few studies have correlated outbreak infections due to C. parapsilosis with virulence factors, such as biofilm production. We thus conducted a microbiological investigation of C. parapsilosis complex isolates from a Brazilian teaching hospital. Additionally, we identified a previously unrecognized outbreak caused by a persistent azole-resistant C. parapsilosis (sensu stricto) clone in the intensive care unit (ICU), correlating it with the main clinical data from the patients with invasive candidiasis. The molecular identification of the isolates was carried out by PCR-RFLP assay; antifungal susceptibility and biofilm formation were also evaluated. The genotyping of all C. parapsilosis (sensu stricto) was performed by microsatellite analysis and the presence of ERG11 mutations was assessed in the azole non-susceptible isolates. Fourteen C. parapsilosis (sensu stricto) isolates were recovered from patients with invasive candidiasis, eight being fluconazole and voriconazole-resistant, and two intermediate only to fluconazole (FLC). All non-susceptible isolates showed a similar pattern of biofilm formation with low biomass and metabolic activity. The A395T mutation in ERG11 was detected exclusively among the azole-resistant isolates. According to the microsatellite analysis, all azole non-susceptible isolates from the adult ICU were clustered together indicating the occurrence of an outbreak. Regarding clinical data, all patients infected by the clonal non-susceptible isolates and none of the patients infected by the susceptible isolates had been previously exposed to corticosteroids (p = 0.001), while the remaining characteristics showed no statistical significance. The current study revealed the persistence of an azole non-susceptible C. parapsilosis clone with low capacity to form biofilm over two years in the adult ICU. These results reinforce the need of epidemiological surveillance and monitoring antifungal susceptibility of C. parapsilosis isolates in hospital wards.

Fluconazole‐resistant Candida parapsilosis strains with a Y132F substitution in the ERG11 gene causing invasive infections in a neonatal unit, South Africa

“…Another substitution, R398I was identified in 92% (36/39) of Y132F isolates. This was a similar occurrence in other studies, suggesting that R398I alone cannot drive or facilitate fluconazole resistance in C parapsilosis isolates but may function to enhance resistance or to stabilise the conformational change derived from the other substitution 12,13,15,25 . Further analysis needs to be undertaken to ascertain the role played by R398I point mutation in fluconazole resistance.…”

Changing epidemiology of candidaemia: Increase in fluconazole‐resistant Candida parapsilosis

“…A possible horizontal yeast transmission by healthcare personnel, as already reported by Delfino et al, could not be excluded. Indeed, outbreaks due to C parapsilosis have been reported, especially in neonatal setting, and in such cases reduced sensitivity and cross‐resistance to triazoles was found . Therefore, patients with resistant C parapsilosis infection might require contact isolation precautions until the clearance of the pathogen.…”

Long-Chain Acyl-CoA Synthetase is Associated with the Growth of Malassezia spp.

“…For the clinical treatment of infectious diseases caused by Malassezia spp., azole drugs such as itraconazole, fluconazole, and ketoconazole, which interfere with sterol synthesis, are frequently used. However, a number of strains of other pathogenic fungi that are resistant to azole drugs have been isolated, like azole-resistant Candida parapsilosis and C. albicans [17,18], and azole-resistant Cryptococcus neoformans [19]. Various azole-resistant M. pachydermatis strains have also been isolated recently [20,21].…”