Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

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Abstract

Introduction

Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI).

Objective

To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.

Design

Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.

Methods

All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.

Results

CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥16 (OR = 6.94, CI _95% = 2.34–20.58, p<0.0001), and liver disease (OR = 186.11, CI _95% = 7.61–4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.

Conclusions

The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.

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Most cited references 24

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Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.

Kevin W. Garey, Milind Rege, Manjunath Pai … (2006)

Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.

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A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.

Peter Pappas, John H Rex, Jeannette Lee … (2003)

We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.

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Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006).

Jean-Pierre Gangneux, Jean-Paul Mira, Jean Carlet … (2009)

To describe the evolving epidemiology, management, and risk factors for death of invasive Candida infections in intensive care units (ICUs). Prospective, observational, national, multicenter study. One hundred eighty ICUs in France. Between October 2005 and May 2006, 300 adult patients with proven invasive Candida infection who received systemic antifungal therapy were included. None. One hundred seven patients (39.5%) with isolated candidemia, 87 (32.1%) with invasive candidiasis without documented candidemia, and 77 (28.4%) with invasive candidiasis and candidemia were eligible. In 37% of the cases, candidemia occurred within the first 5 days after ICU admission. C. albicans accounted for 57.0% of the isolates, followed by C. glabrata (16.7%), C. parapsilosis (7.5%), C. krusei (5.2%), and C. tropicalis (4.9%). In 17.1% of the isolates, the causative Candida was less susceptible or resistant to fluconazole. Fluconazole was the empirical treatment most commonly introduced (65.7%), followed by caspofungin (18.1%), voriconazole (5.5%), and amphotericin B (3.7%). After identification of the causative species and susceptibility testing results, treatment was modified in 86 patients (31.7%). The case fatality ratio in ICU was 45.9% and did not differ significantly according to the type of episode. Multivariate analysis showed that factors independently associated with death in ICU were type 1 diabetes mellitus (odds ratio [OR] 4.51; 95% confidence interval [CI] 1.72-11.79; p = 0.002), immunosuppression (OR 2.63; 95% CI 1.35-5.11; p = 0.0045), mechanical ventilation (OR 2.54; 95% CI 1.33-4.82; p = 0.0045), and body temperature >38.2 degrees C (reference, 36.5-38.2 degrees C; OR 0.36; 95% CI 0.17-0.77; p = 0.008). More than two thirds of patients with invasive candidiasis in ICU present with candidemia. Non-albicans Candida species reach almost half of the Candida isolates. Reduced susceptibility to fluconazole is observed in 17.1% of Candida isolates. Mortality of invasive candidiasis in ICU remains high.

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Author and article information

Contributors

David R. Andes: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 15 May 2014

Volume: 9

Issue: 5

Electronic Location Identifier: e97325

Affiliations

[1 ]Department of Medicine, Salvador Zubiran National Institute of Medical Sciences and Nutrition, Mexico City, Mexico

[2 ]Hospital Escuela, Tegucigalpa, Honduras

[3 ]Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

[4 ]Division of Infectious Diseases, National Cancer Institute, Mexico City, Mexico

[5 ]Department of Internal Medicine, Universidad Nacional de Colombia, Bogota, Colombia

[6 ]Department of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru

[7 ]Infectious Diseases, Hospital Vargas de Caracas and Centro Medico de Caracas, Caracas, Venezuela

[8 ]University Hospital, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

[9 ]Department of Medicine, Memorial Hermann Texas Medical Center, University of Texas Medical School at Houston, Houston, Texas, United States of America

[10 ]Hospital de Clinicas, Universidade Federal do Parana, Curitiba, Brazil

[11 ]Department of Pediatrics, Hospital Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile

[12 ]Department of Medicine, Clinica Alemana, Universidad del Desarrollo, Santiago, Chile

[13 ]Infectious Diseases Unit, Hospital de Clinicas Jose de San Martin, Buenos Aires, Argentina

[14 ]Hospital Vozandes, Facultad de Medicina, Pontificia Universidad Catolica del Ecuador, Quito, Ecuador

University of Wisconsin Medical School, United States of America

Author notes

* E-mail: jose.sifuenteso@ 123456innsz.mx

Competing Interests: The authors have read the journal's policy and have the following conflicts: D. Corzo-Leon has no diclosures; A.L. Colombo has received research grants from Pfizer, MSD, United Medical and Luminex, medical education grants from Pfizer, MSD, United Medical and Astellas. He has also been a consultant for MSD, Pfizer, and Gilead; J.A. Cortes has received research grants and support to attend educational meetings from Pfizer and MSD; M. Nucci has received research grants from Pfizer and MSD and has acted as a consultant and speaker for Pfizer, MSD, Astellas and Gilead; P. Cornejo-Juarez has been a speaker for Merck, Stendhal and Astra Zeneca. She is in an advisory board in Astra-Zeneca and has received research grant from MSD; A Macias has no disclosures; F. de Queiroz-Telles has participated in Continuing education activities in laboratories for Astellas, MSD, Pfizer and United Medical, and in research activities in laboratories for Astellas, MSD and Pfizer; L. Ostrosky-Zeichner has received honoraria for speaking and consulting for Pfizer, Merck, Astellas. He has also recived research grants from Pfizer, Merck, and Astellas; I.N. Tiraboschi has been a speaker for Pfizer and Gilead; J. Zurita has been advisory board member and consultant for Pfizer and has received medical grants from Wyeth and MSD for participating in the SMART study; A. Ponce-de-Leon is speaker on behalf of MSD, Pfizer, Jannsen-Cilag, and Novartis, in addition, he received medical grants funded by MSD and Pfizer and has been an advisory board member for Pfizer, MSD and Jannsen-Cilag; J. Sifuentes-Osornio received grants from Astra-Zeneca, Senosian, Pfizer, MSD, and Sanofi-Pasteur, and is member of advisory board for Pfizer and MSD. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: ALC MN JSO. Performed the experiments: DECL PCJ. Analyzed the data: DECL MN JSO TAM JC JIE MGB FQT MES LTM INT JZ. Contributed reagents/materials/analysis tools: LOZ APL JSO MN ALC. Wrote the paper: DECL PCJ MEM APL MN LOZ JSO.

Article

Publisher ID: PONE-D-13-51355

DOI: 10.1371/journal.pone.0097325

PMC ID: 4022628

PubMed ID: 24830654

SO-VID: 65cb0ca3-d0e1-4bfc-93aa-53eb20101783

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 20 December 2013

Date accepted : 17 April 2014

Page count

Pages: 6

Funding

This study was fully supported by Pfizer Inc. (institutional grant number INF-168). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

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Abstract

Introduction

Objective

Design

Methods

Results

Conclusions

Related collections

PLOS Climate

Most cited references 24

Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.

A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.

Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006).

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