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

Abstract Introduction: Surveillance of Candida 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. Methods: We performed a multicentric retrospective study including all consecutive BC Candida 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. Results: C. albicans was the dominant species (45.1%), while C. auris was undetected. Candida 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 C. albicans (fluconazole from 0.7% to 4.5%, p = 0.03) and C. parapsilosis complex (fluconazole up to 24.5% and voriconazole up to 8.9%), respectively. Resistance to caspofungin was remarkable in C. tropicalis (10%) and C. krusei (20%), while resistance to at least one echinocandin increased in 2021, especially in C. parapsilosis complex (from 0.8% to 5.1%, p = 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. Conclusions: Antifungal stewardship activities aimed at monitoring resistance to echinocandin in C. tropicalis and C. krusei, and against the spread of fluconazole resistant C. parapsilosis complex isolates are highly desirable. In COVID-19 patients, antifungal resistance was mostly present when the illness had a critical course.

[1]  Sameer S. Kadri,et al.  Epidemiology of ICU-Onset Bloodstream Infection: Prevalence, Pathogens, and Risk Factors Among 150,948 ICU Patients at 85 U.S. Hospitals* , 2022, Critical care medicine.

[2]  S. Hawser,et al.  P476 Monitoring antifungal resistance in a global collection of Candida spp. surveillance isolates, including C. auris—analysis of resistance in antifungals (ARIA) 2020 study , 2022, Medical Mycology.

[3]  P. Escribano,et al.  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. , 2022, The Journal of antimicrobial chemotherapy.

[4]  J. Guinea,et al.  Impact of the COVID-19 Pandemic on the Clinical Profile of Candidemia and the Incidence of Fungemia Due to Fluconazole-Resistant Candida parapsilosis , 2022, Journal of fungi.

[5]  K. Pentapati,et al.  Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID‐19) patients: A systematic review , 2022, Mycoses.

[6]  P. Pelosi,et al.  Candida auris Candidemia in Critically Ill, Colonized Patients: Cumulative Incidence and Risk Factors , 2022, Infectious Diseases and Therapy.

[7]  E. Tacconelli,et al.  Surveillance of Antifungal Resistance in Candidemia Fails to Inform Antifungal Stewardship in European Countries , 2022, Journal of fungi.

[8]  Roberto Montalti,et al.  Candidemia in Internal Medicine: Facing the New Challenge , 2021, Mycopathologia.

[9]  P. Le Pape,et al.  Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study , 2021, The Lancet Respiratory Medicine.

[10]  J. Boelens,et al.  Comparison of Two Commercial Colorimetric Broth Microdilution Tests for Candida Susceptibility Testing: Sensititre YeastOne versus MICRONAUT-AM , 2021, Journal of fungi.

[11]  Erica Anderson,et al.  Candida auris Outbreak in a COVID-19 Specialty Care Unit — Florida, July–August 2020 , 2021, MMWR. Morbidity and mortality weekly report.

[12]  P. Pelosi,et al.  Spread of Carbapenem-Resistant Gram-Negatives and Candida auris during the COVID-19 Pandemic in Critically Ill Patients: One Step Back in Antimicrobial Stewardship? , 2021, Microorganisms.

[13]  M. Nucci,et al.  Increased incidence of candidemia in a tertiary care hospital with the COVID‐19 pandemic , 2020, Mycoses.

[14]  A. Lazzarin,et al.  Candidemia in COVID-19 patients: incidence and characteristics in a prospective cohort compared to historical non-COVID-19 controls , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  Mina Kim,et al.  Evaluation of Two Commercial Broth Microdilution Methods Using Different Interpretive Criteria for the Detection of Molecular Mechanisms of Acquired Azole and Echinocandin Resistance in Four Common Candida Species , 2020, Antimicrobial Agents and Chemotherapy.

[16]  S. Pournaras,et al.  Epidemiological Trends of Fungemia in Greece with a Focus on Candidemia during the Recent Financial Crisis: a 10-Year Survey in a Tertiary Care Academic Hospital and Review of Literature , 2019, Antimicrobial Agents and Chemotherapy.

[17]  A. Espinel-Ingroff,et al.  Antifungal Susceptibly Testing by Concentration Gradient Strip Etest Method for Fungal Isolates: A Review , 2019, Journal of fungi.

[18]  M. Wolff,et al.  Diagnosis and Treatment of Candidemia in the Intensive Care Unit , 2019, Seminars in Respiratory and Critical Care Medicine.

[19]  R. Manuel,et al.  Candida auris: a Review of the Literature , 2017, Clinical Microbiology Reviews.

[20]  Ronald N. Jones,et al.  Comparison of EUCAST and CLSI broth microdilution methods for the susceptibility testing of 10 systemically active antifungal agents when tested against Candida spp. , 2014, Diagnostic microbiology and infectious disease.

[21]  J. Guinea Global trends in the distribution of Candida species causing candidemia. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[22]  M. Castanheira,et al.  Frequency of Decreased Susceptibility and Resistance to Echinocandins among Fluconazole-Resistant Bloodstream Isolates of Candida glabrata , 2012, Journal of Clinical Microbiology.

[23]  M. Arendrup Epidemiology of invasive candidiasis , 2010, Current opinion in critical care.

[24]  M. Arendrup,et al.  Echinocandin Susceptibility Testing of Candida Species: Comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, Disk Diffusion, and Agar Dilution Methods with RPMI and IsoSensitest Media , 2009, Antimicrobial Agents and Chemotherapy.

[25]  M. Pfaller,et al.  Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem , 2007, Clinical Microbiology Reviews.

[26]  C. Kibbler,et al.  Candida guilliermondii, an Opportunistic Fungal Pathogen with Decreased Susceptibility to Fluconazole: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program , 2006, Journal of Clinical Microbiology.