In vitro activity of ibrexafungerp against Candida species isolated from blood cultures. Determination of wild type populations using the EUCAST method

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.

Updated analysis on yeast isolates causing fungaemia in patients admitted to a tertiary hospital in Madrid, Spain, over a 13-year period. We studied 896 isolates associated to 872 episodes of fungaemia in 857 hospitalized patients between January 2007 and December 2019. Antifungal susceptibility was assessed by EUCAST EDef 7.3.2. Mutations conferring azole and echinocandin resistance were further studied, and genotyping of resistant clones performed with species-specific microsatellite markers. Candida albicans (45.8%) was the most frequently identified species, followed by the Candida parapsilosis complex (26.4%), Candida glabrata (12.3%), Candida tropicalis (7.3%), Candida krusei (2.3%), other Candida spp. (3.1%), and non-Candida yeasts (2.8%). Rate of fluconazole resistance in Candida spp. was 4.7%, ranging from 0% (C. parapsilosis) to 9.1% (C. glabrata). The overall rate of echinocandin resistance was 3.1%. Resistance was highly influenced by the presence of intrinsically resistant species. Although the number of isolates between 2007 and 2013 was almost two-fold higher than that of the 2014-2019 period (566 vs. 330), fluconazole resistance in Candida spp. was greater in the second period (3.5% vs. 6.8%; P < 0.05), while overall resistance to echinocandins remained stable (3.5% vs. 2.4%; P > 0.05). Resistant clones were collected from different wards and/or time points, suggesting no epidemiological links. The number of fungaemia episodes has been decreasing over the last 13 years, with a slight increase in the rate of fluconazole resistance and stable echinocandin resistance. Antifungal resistance is not the cause of the spread of resistant clones.

Aims: The mechanisms of coronary thrombosis can influence prognosis after STEMI and allow for different treatment groups to be identified; an association between neutrophil extracellular traps (NETs) and unfavorable clinical outcomes has been suggested. Our aim was to determine the role played by NETs in coronary thrombosis and their influence on prognosis. The role of other histological features in prognosis and the association between NETs and bacteria in the coronary thrombi were also explored. Methods and Results: We studied 406 patients with STEMI in which coronary thrombi were consecutively obtained by aspiration during angioplasty between 2012 and 2018. Analysis of NETs in paraffin-embedded thrombi was based on the colocalization of specific NET components by means of confocal microscopy. Immunohistochemistry stains were used to identify plaque fragments. Fluorescence in situ hybridization was used to detect bacteria. NETs were detected in 51% of the thrombi [NET density, median (IQR): 25% (17–38%)]. The median follow-up was 47 months (95% CI 43-51); 105 (26%) patients experienced major adverse cardiac events (MACE). A significant association was found between the presence of NETs in coronary aspirates and the occurrence of MACE in the first 30 days after infarction (HR 2.82; 95% CI 1.26–6.35, p=.012), mainly due to cardiac deaths and stent thrombosis. Conclusions: The presence of NETs in coronary thrombi was associated with a worse prognosis soon after STEMI. In some patients, NETs could be a treatment target and a feasible way to prevent reinfarction.