Abstract
Purpose
Candida is the most common cause of severe yeast infections worldwide, especially in critically ill patients. In this setting, septic shock attributable to Candida is characterized by high mortality rates. The aim of this multicenter study was to investigate the determinants of outcome in critically ill patients with septic shock due to candidemia.
Methods
This was a retrospective study in which patients with septic shock attributable to Candida who were treated during the 3-year study period at one or more of the five participating teaching hospitals in Italy and Spain were eligible for enrolment. Patient characteristics, infection-related variables, and therapy-related features were reviewed. Multiple logistic regression analysis was performed to identify the risk factors significantly associated with 30-day mortality.
Results
A total of 216 patients (mean age 63.4 ± 18.5 years; 58.3 % males) were included in the study. Of these, 163 (75 %) were admitted to the intensive care unit. Overall 30-day mortality was 54 %. Significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, dysfunctional organs, and inadequate antifungal therapy were compared in nonsurvivors and survivors. No differences in survivors versus nonsurvivors were found in terms of the time from positive blood culture to initiation of adequate antifungal therapy. Multivariate logistic regression identified inadequate source control, inadequate antifungal therapy, and 1-point increments in the APACHE II score as independent variables associated with a higher 30-day mortality rate.
Similar content being viewed by others
References
Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C (2005) The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 41(9):1232–1239
Wenzel RP (1995) Nosocomial candidemia: risk factors and attributable mortality. Clin Infect Dis 20(6):1531–1534
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39(3):309–317
Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J, Calandra T, Glauser MP, Tauber MG, Pittet D et al (2004) Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis 38(3):311–320
Bassetti M, Taramasso L, Nicco E, Molinari MP, Mussap M, Viscoli C (2011) Epidemiology, species distribution, antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy. PLoS One 6(9):e24198
Horn DL, Neofytos D, Anaissie EJ, Fishman JA, Steinbach WJ, Olyaei AJ, Marr KA, Pfaller MA, Chang CH, Webster KM (2009) Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis 48(12):1695–1703
Ostrosky-Zeichner L, Pappas PG (2006) Invasive candidiasis in the intensive care unit. Crit Care Med 34(3):857–863
Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302(21):2323–2329
Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3(11):685–702
Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB (2006) Inflammatory response and clinical course of adult patients with nosocomial bloodstream infections caused by Candida spp. Clin Microbiol Infect 12(2):170–177
Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sa M, Johnson EM, Muller E, Putensen C, Rotstein C, Sganga G (2009) Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I. Epidemiology and diagnosis. Intensive Care Med 35(1):55–62
Gutierrez SM, Heredia M, Gomez E, Gomez JI, Tamayo E (2013) Candidemia in ICU patients with sepsis. Crit Care Med 41(11):e385
Delaloye J, Calandra T (2014) Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence 5(1):161–169
Guzman JA, Tchokonte R, Sobel JD (2011) Septic shock due to candidemia: outcomes and predictors of shock development. J Clin Med Res 3(2):65–71
Leroy O, Gangneux JP, Montravers P, Mira JP, Gouin F, Sollet JP, Carlet J, Reynes J, Rosenheim M, Regnier B et al (2009) Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med 37(5):1612–1618
Kollef M, Micek S, Hampton N, Doherty JA, Kumar A (2012) Septic shock attributed toCandida infection: importance of empiric therapy and source control. Clin Infect Dis 54(12):1739–1746
Bassetti M, Molinari MP, Mussap M, Viscoli C, Righi E (2013) Candidaemia in internal medicine departments: the burden of a rising problem. Clin Microb Infect 19(6):E281–E284
Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, Bearden DT (2006) Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 43(1):25–31
Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agenst Chemother 49(9):3640–3645
Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-Akdagli S et al (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microb Infect 18[Suppl 7]:19–37
Reboli AC, Shorr AF, Rotstein C, Pappas PG, Kett DH, Schlamm HT, Reisman AL, Biswas P, Walsh TJ (2011) Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome. BMC Infect Dis 11:261
Bassetti M, Merelli M, Righi E, Diaz-Martin A, Rosello EM, Luzzati R, Parra A, Trecarichi EM, Sanguinetti M, Posteraro B et al (2013) Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol 51(12):4167–4172
Kett DH, Azoulay E, Echeverria PM, Vincent JL (2011) Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in an intensive care unit study. Crit Care Med 39(4):665–670
Ferrada MA, Quartin AA, Kett DH, Morris MI (2013) Candidemia in the critically ill: initial therapy and outcome in mechanically ventilated patients. BMC Anesthesiol 13(1):37
Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, Sobel JD, Pappas PG, Kullberg BJ (2012) 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 54(8):1110–1122
Nucci M, Anaissie E, Betts RF et al (2010) Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin Infect Dis 51:295–303
Acknowledgments
This research was conducted in collaboration with the Critically Ill Patients Study Group (CIPSG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
Conflicts of interest
MB serves on scientific advisory boards for Pfizer Inc, Merck Serono, and Astellas Pharma Inc. and has received funding for travel or speaker honoraria from Pfizer Inc., Merck Serono, Gilead Sciences, Teva Inc and Astellas Pharma Inc. The other authors declare no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Take-home message: High mortality rates were confirmed in patients with Candida-induced septic shock. In this group, the administration of an adequate antifungal therapy along with adequate source control are key factors to improve clinical outcomes.
Rights and permissions
About this article
Cite this article
Bassetti, M., Righi, E., Ansaldi, F. et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 40, 839–845 (2014). https://doi.org/10.1007/s00134-014-3310-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-014-3310-z