Candidemia in Adults at a Tertiary Hospital in China: Clinical Characteristics, Species Distribution, Resistance, and Outcomes
Candidemia is one of the most common nosocomial bloodstream infections. Early diagnosis and antifungal treatment improve clinical outcomes in some studies but not all, with diverse data reported from different institutions. Similarly, antifungal resistance is more common in the USA than in Europe, but there is little data regarding the microbiology and clinical course of candidemia in adult patients in Asia.
(1) To capture species distribution and drug resistance rates among Candida bloodstream isolates, (2) to describe clinical features of candidemia, and (3) to identify factors associated with all-cause mortality, with emphasis on early initiation of antifungal treatment, at a large tertiary University Hospital in China.
In this single-center retrospective study, we identified all patients with candidemia, between 2008 and 2014. Demographic and clinical characteristics, microbiological information, details of antifungal therapy and clinical outcomes were collected.
We studied 166 patients. 71 (42.8%) had cancer. Candida albicans was the most frequent species (37.3%), followed by C. parapsilosis (24.1%), C. tropicalis (22.8%), and C. glabrata (14.5%). Antifungal resistance was more frequent in non-albicans strains and especially C. glabrata. Twenty patients received inappropriate treatment with all-cause mortality of 35%. The remaining 146 patients had significantly lower mortality (21.9%, P = 0.045). Among patients who received antifungal treatment, mortality rate increased with time to appropriate antifungal therapy (AAT): 13.7%, for < 24 h, 21.1% for 24–48 h, 23.1% for > 48 h, and 32.4% among patients who received no AT (χ2 for trend P = 0.039). Initiating AAT more than 24 h after blood culture collection was an independent risk factor for mortality, after adjustment for other confounders (OR 7.1, 95% CI 1.3–39.4, P = 0.024).
Candida albicans was the most frequent cause of candidemia at a large tertiary hospital in China, but antifungal resistance is a growing concern among non-albicans Candida species. The mortality rate of patients treated with ineffective antifungal agents based on in vitro susceptibilities was similar to that of patients who received no treatment at all, and delayed initiation of antifungal treatment was associated with increased risk of death.
KeywordsCandida bloodstream infection Candidemia Antifungal therapy Antifungal resistance Risk factors Clinical outcomes
Appropriate antifungal therapy
Acute physiology and chronic health evaluation
Candida bloodstream infection
Electronic medical record
Inappropriate antifungal therapy
Intensive care unit
Minimal inhibitory concentration(s)
Sequential organ failure assessment
White blood cell count
Charlson weighted index of comorbidities
This work was supported by the Guangdong Natural Science Foundation (Grants 2014A030313305), Science and Technology Planning Project of Guangzhou, Guangdong Province, P. R. China (Grants 201510010046), Science and Technology Planning Project of Guangdong Province, P. R. China (Grants 2015A050502026) and National Natural Science Foundation of China (Grants 81570012) to Xiaojiang Tan. Dr. Farmakiotis has received research support from Astellas Pharma and consultant fees from Viracor. Dr. Mylonakis has received research support from Astellas Pharma and T2 Biosystems. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors have no financial disclosures.
Compliance with Ethical Standards
Conflict of interest
The authors report no conflict of interest. The authors alone are responsible for the content and the writing of the paper.
- 4.Farmakiotis D, Kyvernitakis A, Tarrand JJ, Kontoyiannis DP. Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: a potential benefit from infectious disease consultation. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2015;21(1):79–86.Google Scholar
- 5.Wang E, Farmakiotis D, Yang D, McCue DA, Kantarjian HM, Kontoyiannis DP, et al. The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality. J Antimicrob Chemother. 2015;70(8):2362–8.CrossRefPubMedGoogle Scholar
- 17.Alexander BD, Johnson MD, Pfeiffer CD, Jimenez-Ortigosa C, Catania J, Booker R, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;56(12):1724–32.CrossRefGoogle Scholar
- 20.Vallabhaneni S, Cleveland AA, Farley MM, Harrison LH, Schaffner W, Beldavs ZG, et al. Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based candidemia surveillance program, 2008–2014. Open Forum Infect Dis. 2015;2(4):ofv163.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Delliere S, Healey K, Gits-Muselli M, Carrara B, Barbaro A, Guigue N, et al. Fluconazole and echinocandin resistance of Candida glabrata correlates better with antifungal drug exposure rather than with MSH2 mutator genotype in a French cohort of patients harboring low rates of resistance. Front Microbiol. 2016;7:2038.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Shields RK, Nguyen MH, Press EG, Kwa AL, Cheng S, Du C, et al. The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata. Antimicrob Agents Chemother. 2012;56(9):4862–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J, et al. Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus—United States, May 2013-August 2016. MMWR Morb Mortal Wkly Rep. 2016;65(44):1234–7.CrossRefPubMedGoogle Scholar
- 33.Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, et al. Implementing an antibiotic stewardship program: guidelines by the infectious diseases society of America and the society for healthcare epidemiology of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62(10):e51–77.CrossRefGoogle Scholar
- 34.Lopez-Medrano F, San Juan R, Lizasoain M, Catalan M, Ferrari JM, Chaves F, et al. A non-compulsory stewardship programme for the management of antifungals in a university-affiliated hospital. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2013;19(1):56–61.Google Scholar
- 36.Sipsas NV, Lewis RE, Tarrand J, Hachem R, Rolston KV, Raad II, et al. Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001–2007): stable incidence but changing epidemiology of a still frequently lethal infection. Cancer. 2009;115(20):4745–52.CrossRefPubMedGoogle Scholar
- 40.Le A, Kubiak D, Koo S, Farmakiotis D. Epidemiology of candidemia in hospitalized patients with acute leukemia in the absence of routine antifungal prophylaxis. Open Forum Infect Dis. 2016;3(suppl 1):1597.Google Scholar
- 42.Chiotos K, Vendetti N, Zaoutis TE, Baddley J, Ostrosky-Zeichner L, Pappas P, et al. Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis: a retrospective observational cohort study of the Mycoses Study Group (MSG-12). J Antimicrob Chemother. 2016;71(12):3536–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Fernandez-Ruiz M, Aguado JM, Almirante B, Lora-Pablos D, Padilla B, Puig-Asensio M, et al. Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: a propensity score analysis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2014;58(10):1413–21.CrossRefGoogle Scholar
- 46.Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;54(8):1110–22.CrossRefGoogle Scholar
- 48.Arendrup MC, Boekhout T, Akova M, Meis JF, Cornely OA, Lortholary O, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infections. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2014;20(Suppl 3):76–98.Google Scholar
- 52.Ramos JT, Villar S, Bouza E, Bergon-Sendin E, Perez Rivilla A, Collados CT, et al. Performance of a quantitative PCR-based assay and beta-d-Glucan detection for the diagnosis of invasive candidiasis in very low birth weight preterm neonatal patients (CANDINEO study). J Clin Microbiol. 2017;55(9):2752–64.CrossRefPubMedPubMedCentralGoogle Scholar