Blood and intra-abdominal Candida spp. from a multicentre study conducted in Madrid using EUCAST: emergence of fluconazole resistance in Candida parapsilosis, low echinocandin resistance and absence of Candida auris

Abstract

Objectives We prospectively monitored the epidemiology and antifungal susceptibility of Candida spp. from blood cultures and intra-abdominal samples in patients admitted to hospitals in the Madrid area. Methods Between 2019 and 2021, we prospectively collected incident isolates [one per species, patient and compartment (blood cultures versus intra-abdominal samples)] from patients admitted to any of 16 hospitals located in Madrid. We studied the antifungal susceptibilities to amphotericin B, triazoles, micafungin, anidulafungin and ibrexafungerp following the EUCAST E.Def 7.3.2 procedure. Results A total of 2107 Candida spp. isolates (1895 patients) from blood cultures (51.7%) and intra-abdominal samples were collected. Candida albicans, the Candida glabrata complex, the Candida parapsilosis complex, Candida tropicalis and Candida krusei accounted for 96.9% of the isolates; in contrast, Candida auris was undetected. Fluconazole resistance in Candida spp. was higher in blood cultures than in intra-abdominal samples (9.1% versus 8.2%; P > 0.05), especially for the C. parapsilosis complex (16.6% versus 3.6%, P < 0.05), whereas echinocandin resistance tended to be lower in blood cultures (0.5% versus 1.0%; P > 0.05). Resistance rates have risen, particularly for fluconazole in blood culture isolates, which increased sharply in 2021. Ibrexafungerp showed in vitro activity against most isolates. Species distributions and resistance rates varied among hospitals. Conclusions Whereas no C. auris isolates were detected, fluconazole-resistant C. parapsilosis isolates have been spreading across the region and this has pulled up the rate of fluconazole resistance. In contrast, the rate of echinocandin resistance continues to be low.

Multicentre Surveillance of Candida Species from Blood Cultures during the SARS-CoV-2 Pandemic in Southern Europe (CANCoVEU Project)

“…Although the agreement between the commercial and reference methods for Candida species susceptibility has been described as variable, since it may depend on the antifungals, the species, and the incubation time [ 22 , 23 , 24 , 25 ], our results provided relevant indications. In fact, the remarkable resistance rates to: 1) fluconazole in C. parapsilosis complex (up to 31.2%), C. glabrata (up to 13.5%), and C. guilliermondii (up to 33.3%); 2) EUCAST voriconazole in C. parapsilosis complex (up to 11%); 3) EUCAST and/or CLSI echinocandin in C. tropicalis (up to 12.5%), C. krusei (up to 25%), and C. guilliermondii (up to 33.3%) were consistent with those of both the ARIA project and recent reports analyzing clinical samples from Greece and the Madrid region that highlighted the emergence of fluconazole resistance in C. parapsilosis complex (up to 23%) and a low rate of resistance to echinocandins (up to 1–3%) [ 7 , 15 ]. Our results went into further detail by also highlighting an increase in resistance to fluconazole in C. albicans (up to 4.5%), and fluconazole (up to 24.5%) and echinocandin (up to 5.1%) in C. parapsilosis complex, respectively, despite the reduced frequency of C. parapsilosis complex in 2021.…”

“…Candidemia is one of the most frequent health care-associated bloodstream infections (BSIs) and represents a global clinical challenge, especially given the burden of associated morbidity and mortality [ 1 , 2 ]. Several authors have reported an increase in the incidence of Candida species BSIs during the SARS-CoV-2 pandemic, highlighting the need for active surveillance especially in patients with severe COVID-19 [ 3 , 4 , 5 , 6 , 7 ]. Antibiotic therapy, corticosteroids, immunosuppressive therapy, intravascular devices, long hospital stays, and direct disruption of the intestinal barrier caused by SARS-CoV-2 have been deemed to pave the way to Candida species BSIs [ 4 , 5 ].…”

“…Candida species identification is of paramount importance to promptly optimize antifungal therapy, safeguard the use of more expensive antifungals, de-escalate treatment whenever possible and steer antifungal stewardship efforts. In fact, in addition to C. krusei being intrinsically resistant, resistance to fluconazole was also reported to be remarkable only for C. glabrata [ 12 ], C. guilliermondii [ 13 ], C. auris [ 14 ], and, more recently, in C. parapsilosis complex [ 6 , 7 , 15 ].…”

Questioning the 14‐day dogma in candidemia treatment duration

“…This approach becomes particularly pertinent in light of the increasing prevalence of Candida glabrata , Candida parapsilosis and multiresistant Candida auris 6,16 . And this concern becomes even more pronounced when transitioning from newer antifungal agents like echinocandins to oral alternatives such as fluconazole in which the emergence of drug resistance is a more obvious phenomenon 7,8,28 . A well‐considered approach to adequate antifungal selection 29 is crucial to forestall the potential development of resistant strains, especially in the context of fluconazole usage, which has already been associated with the emergence of multiresistant species.…”

Clonal spread of fluconazole‐resistant C. parapsilosis in patients admitted to a referral hospital located in Burgos, Spain, during the COVID‐19 pandemic

“…8 Isolates harbouring the G458S substitution were recently detected in a hospital located in Madrid in late 2021. [9][10][11] Phenotypic FRCP was detected for the first time in April 2021, in patients admitted to a referral hospital in Burgos, a city located in Northern Spain. We here report the spread of such isolates across the hospital and describe a new outbreak caused by FCRP isolates in a hospital in Spain.…”