Trends in antifungal resistance in Candida from a multicenter study conducted in Madrid (CANDIMAD study): fluconazole-resistant C. parapsilosis spreading has gained traction in 2022

Abstract

We previously conducted a multicenter surveillance study on Candida epidemiology and antifungal resistance in Madrid (CANDIMAD study; 2019-2021), detecting an increase in fluconazole-resistant Candida parapsilosis. We here present data on isolates collected in 2022. Furthermore, we report the epidemiology and antifungal resistance trends during the entire period, including an analysis per ward of admission. Candida spp. incident isolates from blood cultures and intra-abdominal samples from patients cared for at 16 hospitals in Madrid, Spain, were tested with the EUCAST E.Def 7.3.2 method against amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp and were molecularly characterized. In 2022, we collected 766 Candida sp. isolates (686 patients; blood cultures, 48.8%). Candida albicans was the most common species found, and Candida auris was undetected. No resistance to amphotericin B was found. Overall, resistance to echinocandins was low (0.7%), whereas fluconazole resistance was 12.0%, being higher in blood cultures (16.0%) mainly due to fluconazole-resistant C. parapsilosis clones harboring the Y132F-R398I ERG11p substitutions. Ibrexafungerp showed in vitro activity against the isolates tested. Whereas C. albicans was the dominant species in most hospital wards, we observed increasing C. parapsilosis proportions in blood. During the entire period, echinocandin resistance rates remained steadily low, while fluconazole resistance increased in blood from 6.8% (2019) to 16% (2022), mainly due to fluconazole-resistant C. parapsilosis (2.6% in 2019 to 36.6% in 2022). Up to 7 out of 16 hospitals were affected by fluconazole-resistant C. parapsilosis. In conclusion, rampant clonal spreading of C. parapsilosis fluconazole-resistant genotypes is taking place in Madrid.

Keywords: C. parapsilosis; Candida; Madrid; Y132F; antifungal resistance.

Fig 1

Species distributions and resistance rates per year in Candida sp. isolates from (a) blood cultures and (b) intra-abdominal samples. *Isolates collected in 2022. Blood cultures: C. parapsilosis complex (C. parapsilosis sensu stricto, n = 134; and C. orthopsilosis, n = 1); Candida spp. (C. lusitaniae, n = 3; C. guilliermondii, n = 1; and C. pararugosa, n = 1); non-Candida (Saccharomyces cerevisiae, n = 2; Rhodotorula mucilaginosa, n = 2; and Cryptococcus neoformans, n = 1), which represented 1.3% of blood isolates. Intra-abdominal samples: C. parapsilosis complex (C. parapsilosis sensu stricto, n = 39; and C. orthopsilosis, n = 1); Candida spp. (C. lusitaniae, n = 11; C. dubliniensis, n = 4; C. guilliermondii, n = 3; C. pararugosa, n = 1; and C. inconspicua, n = 1); non-Candida (Pichia manshurica, n = 1; Wickerhamomyces onychis, n = 1), which represented 0.5% of intra-abdominal isolates. Non-Candida isolates were excluded from the analysis. Adapted from a previously reported publication (12); reprinted with the journal’s permission (license number: 5623520933072); data from 2022 are here newly reported.

Fig 2

Minimum spanning tree showing fluconazole-resistant C. parapsilosis genotypes found during the study period (2019–2022) per year of detection (A) or per hospital (B) Circles represent different genotypes, and circle size, the number of isolates belonging to the same genotype. Connecting lines between the circles show profile similarities. The solid bold line indicates differences in only one marker, and the dotted line indicates differences in four or more markers. Genotypes CP-673, CP-674, CP-707, and CP-795 differ from CP-451 at microsatellite markers B, CP6, CP4a, and CP6, respectively.

Fig 3

Species distributions and resistance rates of Candida spp. isolates from blood cultures per ward of admission during the 2019–2022 period.

Fig 4

Timeline of the detection of fluconazole-resistant C. parapsilosis isolates at each affected hospital over the 4-year study period. Colored symbols refer to fluconazole-resistant C. parapsilosis isolates from blood cultures, an asterisk represents isolates from intra-abdominal samples. Red indicates isolates within the clonal complex (CP-451, bar; CP-673, oval; CP-674, triangle; CP-707, star; and CP-795, moon) of genotypes harboring the Y132F-R398I ERG11p substitution. Blue indicates isolates within the CP-675 genotype harboring the G458S substitution. Arrow indicates the first time resistant isolates were detected. Adapted from a previously reported figure (11); reprinted with the journal’s permission (order license ID: 1397047–1); data from 2022 are here newly reported.