Abstract
Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW’s hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW’s hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW’s hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.
Highlights
Candidemia has shown a high mortality rate and increasing incidence mainly in patients with malignancy, immune impairment, and use of invasive devices
Candida parapsilosis is known to be susceptible to azole-class drugs; emerging studies have implicated the surge of clonal outbreaks as due to azole-resistant C. parapsilosis (ARCP) isolates in numerous countries [10,11,12,13,14,15], possibly fueled by azole overuse, which complicates the treatment of azole-naïve patients and is potentially associated with a higher mortality rate [16]
Antifungal susceptibility and genetic profiles were determined for 112 isolates obtained in 2019, including 73 clinical isolates (70 from blood cultures and 3 from pericatheter skins), 28 healthcare workers (HCW) isolates (27 from hands and 1 from a skin lesion), and 11 nosocomial surface isolates (7 from bedside carts, 2 from bedrails, 1 from an infusion pump, and 1 from a cardiac monitor)
Summary
Candidemia has shown a high mortality rate and increasing incidence mainly in patients with malignancy, immune impairment, and use of invasive devices. Treatment, prophylaxis, and infection control have improved, invasive infections caused by Candida parapsilosis are still regarded as a medical emergency for susceptible patients, including those suffering from cancer [1,2,3]. Candida albicans remains the most frequent cause of candidemia, the extensive antifungal exposure may lead to the emergence of non-albicans Candida species [4,5]. Candida parapsilosis is known to be susceptible to azole-class drugs; emerging studies have implicated the surge of clonal outbreaks as due to azole-resistant C. parapsilosis (ARCP) isolates in numerous countries [10,11,12,13,14,15], possibly fueled by azole overuse, which complicates the treatment of azole-naïve patients and is potentially associated with a higher mortality rate [16]. More alarming is the emergence of multidrug-resistant (MDR) C. parapsilosis isolates, resistant to both of the most widely used frontline antifungals, i.e., fluconazole and echinocandins [17], and the lack of effectiveness of these drugs against C. parapsilosis biofilms [18]
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