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Impact of Therapeutic Strategies on the Prognosis of Candidemia in the ICU*

Puig-Asensio, Mireia MD1; Pemán, Javier MD2; Zaragoza, Rafael MD3; Garnacho-Montero, José PhD4; Martín-Mazuelos, Estrella MD5; Cuenca-Estrella, Manuel MD6; Almirante, Benito MD1

doi: 10.1097/CCM.0000000000000221
Clinical Investigations

Objectives: To determine the epidemiology of Candida bloodstream infections, variables influencing mortality, and antifungal resistance rates in ICUs in Spain.

Design: Prospective, observational, multicenter population-based study.

Setting: Medical and surgical ICUs in 29 hospitals distributed throughout five metropolitan areas of Spain.

Patients: Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during admission to any surveillance area ICU from May 2010 to April 2011.

Interventions: Candida isolates were sent to a reference laboratory for species identification by DNA sequencing and susceptibility testing using the methods and breakpoint criteria promulgated by the European Committee on Antimicrobial Susceptibility Testing. Prognostic factors associated with early (0–7 d) and late (8–30 d) mortality were analyzed using logistic regression modeling.

Measurements and Main Results: We detected 773 cases of candidemia, 752 of which were included in the overall cohort. Among these, 168 (22.3%) occurred in adult ICU patients. The rank order of Candida isolates was as follows: Candida albicans (52%), Candida parapsilosis (23.7%), Candida glabrata (12.7%), Candida tropicalis (5.8%), Candida krusei (4%), and others (1.8%). Overall susceptibility to fluconazole was 79.2%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 16.5% and 47%, respectively. Multivariate analysis showed that early appropriate antifungal treatment and catheter removal (odds ratio, 0.27; 95% CI, 0.08–0.91), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.11; 95% CI, 1.04–1.19), and abdominal source (odds ratio, 8.15; 95% CI, 1.75–37.93) were independently associated with early mortality. Determinants of late mortality were age (odds ratio, 1.04; 95% CI, 1.01–1.07), intubation (odds ratio, 7.24; 95% CI, 2.24–23.40), renal replacement therapy (odds ratio, 6.12; 95% CI, 2.24–16.73), and primary source (odds ratio, 2.51; 95% CI, 1.06–5.95).

Conclusions: Candidemia in ICU patients is caused by non-albicans species in 48% of cases, C. parapsilosis being the most common among these. Overall mortality remains high and mainly related with host factors. Prompt adequate antifungal treatment and catheter removal could be critical to decrease early mortality.

1Infectious Diseases Department, Hospital Universitari Vall d´Hebron, Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain.

2Microbiology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

3Intensive Care Medicine Department, Hospital Universitario Dr. Peset, Valencia, Spain.

4Critical Care and Emergency Department, Hospital Universitario Virgen del Rocío, Seville, Spain.

5Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Instituto de Biomedicina de Sevilla (IbiS), Seville, Spain.

6Department of Mycology, Spanish National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

* See also p. 1554.

Members of the CANDIPOP Project, GEIH, GEMICOMED (SEIMC), and Spanish Network for Research in Infectious Diseases are listed in the Acknowledgments section.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

The Spanish Society of Infectious Diseases and Clinical Microbiology-Spanish Aids Study Group (SEIMC-GESIDA) Foundation provided methodological support. Supported by research grants from Gilead, MSD, Astellas and Pfizer and by funding from Ministerio de Economia y Competitividad, Instituto de Salud Carlos III, - cofinanced by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD 12/0015).

Dr. Pemán has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, and Astellas and a grant support from Pfizer and Astellas. Dr. Zaragoza provided expert testimony for MSD and lectured for MSD, Pfizer, Astellas, and Gilead. Dr. Zaragoza has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, and Astellas and grant support from Pfizer. Dr. Garnacho-Montero has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, and Astellas. Dr. Cuenca-Estrella consulted for, lectured for, received grant support from, and received support for development of educational presentations from MSD, Gilead, Pfizer, and Astellas. His institution received grant support from MSD, Gilead, Pfizer, and Astellas. Dr. Cuenca-Estrella has received grant support from Astellas Pharma, bioMerieux, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Schering Plough, Soria Melguizo SA, Ferrer International, the European Union, the ALBAN program, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, The Spanish Health Research Fund, The Instituto de Salud Carlos III, The Ramon Areces Foundation, and The Mutua Madrileña Foundation. He has been an advisor/consultant to the Panamerican Health Organization, Astellas Pharma, Gilead Sciences, Merck Sharp and Dohme, Pfizer, and Schering Plough. He has been paid for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, Astellas Pharma, and Schering Plough. Dr. Almirante lectured for Gilead Sciences, Merck Sharp and Dohme, Pfizer, Astellas, and Novartis. Dr. Almirante and his institution received grant support from Gilead Sciences, Pfizer, and the Instituto de Salud Carlos III. He has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, Astellas, and Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: balmirante@vhebron.net

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins