, Volume 182, Issue 7–8, pp 665–672 | Cite as

Factors Influencing Non-albicans Candidemia: A Case–Case–Control Study

  • Diamantis P. Kofteridis
  • Antonis Valachis
  • Dimitra Dimopoulou
  • Angeliki M. Andrianaki
  • Athanasia Christidou
  • Sofia Maraki
  • Nikolaos A. Spernovasilis
  • George Samonis


The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case–case–control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.


Candidemia C. albicans Non-albicans Candida spp. Carbapenems b-Lactam-b-lactamase inhibitors Quinolones 



Presented in part at 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 9–12, 2012; San Francisco, California.


This study has been supported by the Hellenic Society for Medical Mycology (Grant number 557A / 07-04-2014).

Compliance with Ethical Standards

Conflict of interest



  1. 1.
    Wisplinhoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:309–17.CrossRefGoogle Scholar
  2. 2.
    Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41:1232–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Fraser VJ, Jones M, Dunkel J, et al. Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis. 1992;15:414–21.CrossRefPubMedGoogle Scholar
  4. 4.
    Nguyen MH, Peacock JE Jr, Tanner DC, et al. Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study. Arch Intern Med. 1995;155:2429–35.CrossRefPubMedGoogle Scholar
  5. 5.
    Nucci M, Colombo AL, Silveira F, et al. Risk factors for death in patients with candidemia. Infect Control Hosp Epidemiol. 1998;19:846–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Hajjeh RA, Sofair AN, Harrison LH, et al. Incidence of bloodstream infections due to Candida species and invitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol. 2004;42:1519–27.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hope W, Morton A, Eisen DP. Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use. J Hosp Infect. 2002;50:56–65.CrossRefPubMedGoogle Scholar
  8. 8.
    Yamamura DL, Rotstein C, Nicole LE, Ioannou S. Candidemia at selected Canadian sites: results from the Fungal Disease Registry, 1992–1994. Fungal Disease Registry of the Canadian Infectious Disease Society. Canadian Med Assoc J. 1999;160:493–9.Google Scholar
  9. 9.
    Viscoli C, Girmenia Marinus A, et al. Candidemia in cancer patients: a prospective, multicenter surveillance study by the invasive fungal infection group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis. 1999;28:1071–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Colombo AL, Nucci M, Salomao R, et al. High rate of non-albicans candidemia in Brazilian tertiary care hospitals. Diagn Microbiol Infect Dis. 1999;34:281–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Pfaller MA, Diekema DJ. Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida. Clin Microbiol Infect. 2004;10(Suppl 1):11–23.CrossRefPubMedGoogle Scholar
  12. 12.
    Orozco AS, Higginbotham LM, Hitchcock CA, et al. Mechanism of fluconazole resistance in Candida krusei. Antimicrob Agents Chemother. 1998;42:2645–9.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Spellberg BJ, Filler SG, Edwards JE Jr. Current treatment strategies for disseminated candidiasis. Clin Infect Dis. 2006;42:244–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Ben-Ami R, Olshtain-Pops K, Krieger M, Israeli Candidemia Study Group, et al. Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection. Antimicrob Agents Chemother. 2012;56:2518–23.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chi HW, Yang YS, Shang ST, et al. Candida albicans versus non-albicans bloodstream infections: the comparison of risk factors and outcome. J Microbiol Immunol Infect. 2011;44:369–75.CrossRefPubMedGoogle Scholar
  16. 16.
    Garnacho-Montero J, Díaz-Martín A, García-Cabrera E, et al. Risk factors for fluconazole-resistant candidemia. Antimicrob Agents Chemother. 2010;54:3149–54.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Rodríguez D, Almirante B, Cuenca-Estrella M, Rodríguez-Tudela JL, Mensa J, Ayats J, Sanchez F, Pahissa A, Barcelona Candidemia Project Study Group. Predictors of candidaemia caused by non-albicans Candida species: results of a population-based surveillance in Barcelona, Spain. Clin Microbiol Infect. 2010;16:1676–82.CrossRefPubMedGoogle Scholar
  18. 18.
    Davis SL, Vazquez JA, McKinnon PS. Epidemiology, risk factors, and outcomes of Candida albicans versus non-albicans candidemia in non neutropenic patients. Ann Pharmacother. 2007;41:568–73.CrossRefPubMedGoogle Scholar
  19. 19.
    Lin MY, Carmeli Y, Zumsteg J, et al. Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case–case–control study. Antimicrob Agents Chemother. 2005;49:4555–60.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Yapar N, Pullukcu H, Avkan-Oguz V, et al. Evaluation of species distribution and risk factors of candidemia: a multicenter case–control study. Med Mycol. 2011;49:26–31.CrossRefPubMedGoogle Scholar
  21. 21.
    Kaye KS, Harris AD, Samore M, Carmeli Y. The case–case–control study design: addressing the limitations of risk factor studies for antimicrobial resistance. Infect Control Hosp Epidemiol. 2005;26:346–51.CrossRefPubMedGoogle Scholar
  22. 22.
    Samonis G, Gikas A, Anaissie EJ, et al. Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob Agents Chemother. 1993;37:51–3.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Pultz NJ, Stiefel U, Ghannoum M, Helfand MS, Donskey CJ. Effect of parenteral antibiotic administration on establishment of intestinal colonization by Candida glabrata in adult mice. Antimicrob Agents Chemother. 2005;49:438–40.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cole GT, Halawa AA, Anaissie EJ. The role of the gastrointestinal tract in hematogenous candidiasis: from the laboratory to the bedside. Clin Infect Dis. 1996;22(Suppl 2):S73–88.CrossRefPubMedGoogle Scholar
  25. 25.
    Samonis G, Maraki S, Leventakos K, et al. Comparative effects of ertapenem, imipenem, and meropenem on the colonization of the gastrointestinal tract of mice by Candida albicans. Med Mycol. 2006;44:233–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Maraki S, Lionakis S, Ntaoukakis M, et al. Effects of levofloxacin, moxifloxacin and prulifloxacin on murine gut colonization by Candida albicans. Med Mycol. 2011;49:419–23.CrossRefPubMedGoogle Scholar
  27. 27.
    Chow JK, Golan Y, Ruthazer R, et al. Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit. Clin Infect Dis. 2008;46:1206–13.CrossRefPubMedGoogle Scholar
  28. 28.
    Dimopoulos G, Ntziora F, Rachiotis G, Armaganidis A, Falagas ME. Candida albicans versus non-albicans intensive care unit-acquired bloodstream infections: differences in risk factors and outcome. Anesth Analg. 2008;106:523–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Diamantis P. Kofteridis
    • 1
  • Antonis Valachis
    • 3
    • 4
  • Dimitra Dimopoulou
    • 1
  • Angeliki M. Andrianaki
    • 1
  • Athanasia Christidou
    • 2
  • Sofia Maraki
    • 2
  • Nikolaos A. Spernovasilis
    • 1
  • George Samonis
    • 1
  1. 1.Infectious Disease Unit, Department of Internal MedicineUniversity Hospital of HeraklionHeraklionGreece
  2. 2.Clinical MicrobiologyUniversity Hospital of HeraklionHeraklionGreece
  3. 3.Department of OncologyMälarsjukhusetEskilstunaSweden
  4. 4.University of UppsalaUppsalaSweden

Personalised recommendations