| Summary: | <b>Introduction</b>: Surveillance of <i>Candida</i> species isolates from blood cultures (BCs) in Europe is considered fragmented, unable to allow the definition of targets of antifungal stewardship recommendations especially during the SARS-CoV-2 pandemic. <b>Methods</b>: We performed a multicentric retrospective study including all consecutive BC <i>Candida</i> isolates from six Southern European tertiary hospitals (1st January 2020 to 31st December 2021). Etiology, antifungal susceptibility patterns, and clinical setting were analyzed and compared. <b>Results</b>: <i>C. albicans</i> was the dominant species (45.1%), while <i>C. auris</i> was undetected. <i>Candida</i> species positive BC events increased significantly in COVID-19 ICUs in 2021 but decreased in other ICUs. Resistance to azole increased significantly and remained very high in <i>C. albicans</i> (fluconazole from 0.7% to 4.5%, <i>p</i> = 0.03) and <i>C. parapsilosis</i> complex (fluconazole up to 24.5% and voriconazole up to 8.9%), respectively. Resistance to caspofungin was remarkable in <i>C. tropicalis</i> (10%) and <i>C. krusei</i> (20%), while resistance to at least one echinocandin increased in 2021, especially in <i>C. parapsilosis</i> complex (from 0.8% to 5.1%, <i>p</i> = 0.05). Although no significant differences were observed over the study period, fluconazole and echinocandin resistance increased in COVID-19 ICUs by up to 14% and 5.8%, respectively, but remained undetected in non-intensive COVID-19 wards. <b>Conclusions</b>: Antifungal stewardship activities aimed at monitoring resistance to echinocandin in <i>C. tropicalis</i> and <i>C. krusei</i>, and against the spread of fluconazole resistant <i>C. parapsilosis</i> complex isolates are highly desirable. In COVID-19 patients, antifungal resistance was mostly present when the illness had a critical course.
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