{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:01:20Z","timestamp":1789621280265,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Candida spp. can cause bloodstream infection and is associated with significant mortality. The proportion of fluconazole-resistant Candida non-albicans has increased over the years, and empirical fluconazole maybe inappropriate. In this retrospective study, we analyzed clinical characteristics, antifungal resistance patterns, and mortality in children with candidemia treated at a tertiary medical center in Jerusalem between 2009 and 2022. A total of 122 children developed 127 candidemia episodes with 132 Candida isolates. Half the episodes occurred in immunocompromised children. Septic shock was present in 27 (21.3%). Candida non-albicans was responsible for 71\/132 (56.5%) episodes; 16\/132 (12.1%) of isolates were fluconazole-resistant. The rate of Candida non-albicans was significantly higher in fluconazole-resistant episodes (90 vs. 50.5%, p = 0.02). Prolonged severe neutropenia and previous fluconazole exposure were more frequent in fluconazole-resistant episodes. Thirty-day mortality was 25 (19.7%). Greater mortality, as shown by multivariate analysis, was associated with candidemia contracted in the pediatric intensive care unit (PICU), previous use of azoles or carbapenems, and in the presence of shock. In conclusion, mortality rates in our study were higher than those previously reported. In suspected infection associated with factors which we found to increase the probability of mortality\u2014PICU admission, shock, and earlier azole or carbapenems exposure\u2014empirical antifungals should be considered.<\/jats:p>","DOI":"10.3390\/jof9121171","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T03:48:41Z","timestamp":1701834521000},"page":"1171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A 14-Year Cohort of Candidemia in the Pediatric Population in a Tertiary Center in Jerusalem: Clinical Characteristics, Antifungal Susceptibility, and Risk Factors for Mortality"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-0963","authenticated-orcid":false,"given":"Maya","family":"Korem","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Department of Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher","family":"Taragin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Infectious Diseases, Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danna","family":"Dror","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Department of Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Temper","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Department of Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Averbuch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Infectious Diseases, Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e78","DOI":"10.1093\/jpids\/piy009","article-title":"Neonatal and Pediatric Candidemia: Results from Population-Based Active Laboratory Surveillance in Four US Locations, 2009\u20132015","volume":"7","author":"Benedict","year":"2018","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/clind\/15.3.414","article-title":"Candidemia in a tertiary care hospital: Epidemiology, risk factors, and predictors of mortality","volume":"15","author":"Fraser","year":"1992","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/INF.0000000000002207","article-title":"Pediatric Candidemia Epidemiology and Morbidities: A Nationwide Cohort","volume":"38","author":"Lausch","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/s41598-017-01123-6","article-title":"Clinical and microbiological characteristics, and impact of therapeutic strategies on the outcomes of children with candidemia","volume":"7","author":"Tsai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kumar, R., and Srivastava, V. (2023). Application of anti-fungal vaccines as a tool against emerging anti-fungal resistance. Front. Fungal Biol., 4.","DOI":"10.3389\/ffunb.2023.1241539"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1590\/0074-02760150335","article-title":"New insights on the development of fungal vaccines: From immunity to recent challenges","volume":"110","author":"Medici","year":"2015","journal-title":"Mem. Do Inst. Oswaldo Cruz"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Walker, J., Edwards, W.S., Hall, N.M., and Pappas, P.G. (2023). Challenges in management of invasive fungal infections in stem cell transplant. Transpl. Infect. Dis. Off. J. Transplant. Soc., e14175.","DOI":"10.1111\/tid.14175"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S394","DOI":"10.1093\/cid\/ciaa1523","article-title":"Clinical Characteristics and Outcomes of Breakthrough Candidemia in 71 Hematologic Malignancy Patients and\/or Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-Center Retrospective Study from China, 2011\u20132018","volume":"71","author":"Chen","year":"2020","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Brunetti, G., Navazio, A.S., Giuliani, A., Giordano, A., Proli, E.M., Antonelli, G., and Raponi, G. (2019). Candida blood stream infections observed between 2011 and 2016 in a large Italian University Hospital: A time-based retrospective analysis on epidemiology, biofilm production, antifungal agents consumption and drug-susceptibility. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224678"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Israel, S., Amit, S., Israel, A., Livneh, A., Nir-Paz, R., and Korem, M. (2019). The Epidemiology and Susceptibility of Candidemia in Jerusalem, Israel. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00352"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1093\/ofid\/ofy358","article-title":"Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species from 1997\u20132016","volume":"6","author":"Pfaller","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1128\/AAC.00479-10","article-title":"Risk factors for fluconazole-resistant candidemia","volume":"54","author":"Cisneros","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","unstructured":"CLSI (2020). Performance Standards for Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute."},{"key":"ref_15","unstructured":"CLSI (2017). Reference Method for Broth Microdilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and Update of the Consensus Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1128\/JCM.40.3.852-856.2002","article-title":"Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000","volume":"40","author":"Pfaller","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.4103\/1947-2714.118919","article-title":"Emergence of non-albicans Candida species in neonatal candidemia","volume":"5","author":"Juyal","year":"2013","journal-title":"North Am. J. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/INF.0000000000003082","article-title":"Candidemia in Children: A 16-year Longitudinal Epidemiologic Study","volume":"40","author":"Silvester","year":"2021","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Whaley, S.G., Berkow, E.L., Rybak, J.M., Nishimoto, A.T., Barker, K.S., and Rogers, P.D. (2016). Azole Antifungal Resistance in Candida albicans and Emerging Non-Albicans Candida Species. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.02173"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"624","DOI":"10.3855\/jidc.4186","article-title":"Characteristics and risk factors of candidemia in pediatric intensive care unit of a tertiary care children\u2019s hospital in Egypt","volume":"8","author":"Hegazi","year":"2014","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/INF.0000000000002530","article-title":"Etiology and Outcome of Candidemia in Neonates and Children in Europe: An 11-Year Multinational Retrospective Study","volume":"39","author":"Warris","year":"2020","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Piqueras, A., Ganapathi, L., Carpenter, J.F., Rubio, T., Sandora, T.J., Flett, K.B., and Kohler, J.R. (2021). Trends in Pediatric Candidemia: Epidemiology, Anti-Fungal Susceptibility, and Patient Characteristics in a Children\u2019s Hospital. J. Fungi, 7.","DOI":"10.3390\/jof7020078"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1542\/peds.2008-2055","article-title":"Not just little adults: Candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients","volume":"123","author":"Blyth","year":"2009","journal-title":"Pediatrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1093\/infdis\/167.5.1247","article-title":"Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System","volume":"167","author":"Jarvis","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.jfma.2021.11.009","article-title":"Comparisons of the clinical and mycological characteristics of pediatric candidemia","volume":"121","author":"Chen","year":"2022","journal-title":"J. Formos. Med. Assoc. Taiwan Yi Zhi"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1111\/myc.13145","article-title":"Characteristics, outcome and risk factors for mortality of paediatric patients with ICU-acquired candidemia in India: A multicentre prospective study","volume":"63","author":"Chakrabarti","year":"2020","journal-title":"Mycoses"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1128\/AAC.05947-11","article-title":"Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection","volume":"56","author":"Krieger","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","first-page":"49","article-title":"Epidemiology, microbiology, clinical characteristics, and outcomes of candidemia in internal medicine wards-a retrospective study","volume":"52","author":"Babaoff","year":"2016","journal-title":"Int. J. Infect. Dis. IJID Off. Publ. Int. Soc. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1128\/JCM.06112-11","article-title":"Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata","volume":"50","author":"Pfaller","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.diagmicrobio.2014.02.008","article-title":"The impact of new epidemiological cutoff values on Candida glabrata resistance rates and concordance between testing methods","volume":"79","author":"Hilerowicz","year":"2014","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/IDR.S118892","article-title":"Fluconazole resistance in Candida species: A current perspective","volume":"10","author":"Berkow","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1128\/AAC.01177-15","article-title":"Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae","volume":"59","author":"Souza","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1007\/s00134-002-1540-y","article-title":"Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: A randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination","volume":"28","author":"Garbino","year":"2002","journal-title":"Intensive Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1097\/INF.0b013e3182737427","article-title":"Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates","volume":"31","author":"Steinbach","year":"2012","journal-title":"Pediatr. Infect. Dis. J."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/12\/1171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:50Z","timestamp":1760132030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/12\/1171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["jof9121171"],"URL":"https:\/\/doi.org\/10.3390\/jof9121171","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]}}}