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Candidemia in non-ICU surgical wards: Comparison with medical wards

  • Antonio Vena ,

    Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Writing – original draft, Writing – review & editing

    pmunoz@micro.hggm.es (PM); anton.vena@gmail.com (AV)

    Affiliations Clinical Microbiology and Infectious Disease Division, Hospital General Universitario Gregorio Marañón, Madrid, Spain, Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain, Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain, Clinica Malattie Infettive AOU Santa Maria della Misericordia Piazzale Santa Maria della Misericordia, Udine, Italy

  • Emilio Bouza,

    Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Resources, Supervision, Validation, Writing – original draft, Writing – review & editing

    Affiliations Clinical Microbiology and Infectious Disease Division, Hospital General Universitario Gregorio Marañón, Madrid, Spain, Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain, Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain

  • Maricela Valerio,

    Roles Data curation

    Affiliations Clinical Microbiology and Infectious Disease Division, Hospital General Universitario Gregorio Marañón, Madrid, Spain, Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain, Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain

  • Belén Padilla,

    Roles Data curation

    Affiliation Clinical Microbiology and Infectious Disease Division, Hospital General Universitario Gregorio Marañón, Madrid, Spain

  • José Ramón Paño-Pardo,

    Roles Data curation

    Affiliation Hospital Universitario La Paz, Madrid, Spain

  • Mario Fernández-Ruiz,

    Roles Data curation

    Affiliation Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain

  • Ana Díaz Martín,

    Roles Data curation

    Affiliation Servicio Andaluz de Salud, UGC-SCCU, Sevilla, Andalucía, Spain

  • Miguel Salavert,

    Roles Data curation

    Affiliation Hospital Universitario y Politécnico La Fe, Valencia, Spain

  • Alessandra Mularoni,

    Roles Data curation

    Affiliation Istituto mediterraneo per i trapianti e terapie ad alta specializzazione ISMETT-UPMC, Palermo, Italy

  • Mireia Puig-Asensio,

    Roles Data curation

    Affiliation Hospital Universitario Vall d'Hebron, Barcelona, Spain

  • Patricia Muñoz ,

    Roles Data curation, Formal analysis, Funding acquisition, Project administration, Resources, Writing – original draft, Writing – review & editing

    pmunoz@micro.hggm.es (PM); anton.vena@gmail.com (AV)

    Affiliations Clinical Microbiology and Infectious Disease Division, Hospital General Universitario Gregorio Marañón, Madrid, Spain, Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain, Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain

  • for the CANDIPOP Project

    Complete membership of the author group can be found in the Acknowledgments section.

Candidemia in non-ICU surgical wards: Comparison with medical wards

  • Antonio Vena, 
  • Emilio Bouza, 
  • Maricela Valerio, 
  • Belén Padilla, 
  • José Ramón Paño-Pardo, 
  • Mario Fernández-Ruiz, 
  • Ana Díaz Martín, 
  • Miguel Salavert, 
  • Alessandra Mularoni, 
  • Mireia Puig-Asensio
PLOS
x

Abstract

Candidemia acquired outside critical care or hematological areas has received much attention in recent years; however, data on candidemia in surgical departments are very scarce. Our objectives were to describe episodes of candidemia diagnosed in surgical wards and to compare them with episodes occurring in medical wards. We performed a post hoc analysis of a prospective, multicenter study implemented in Spain during 2010–2011 (CANDIPOP project). Of the 752 episodes of candidemia, 369 (49.1%) occurred in patients admitted to surgical wards (165, 21.9%) or medical wards (204, 27.2%). Clinical characteristics associated with surgical patients were solid tumor as underlying disease, recent surgery, indwelling CVC, and parenteral nutrition. Candidemia was more commonly related to a CVC in the surgical than in the medical wards. The CVC was removed more frequently and early management was more appropriate within 48 hours of blood sampling in the surgical patients. Overall, 30-day mortality in the surgical departments was significantly lower than in medical wards (37.7% vs. 15.8%, p<0.001). Multivariate analysis revealed admission to a surgical ward and appropriate early management of candidemia as factors independently associated with a better outcome. We found that approximately 50% of episodes of candidemia occurred in non-hematological patients outside the ICU and that clinical outcome was better in patients admitted to surgical wards than in those hospitalized in medical wards. These findings can be explained by the lower severity of underlying disease, prompt administration of antifungal therapy, and central venous catheter removal.

Introduction

Candidemia is a leading cause of nosocomial bloodstream infections[1, 2] and has a high attributable mortality[36]. Most series have addressed the characteristics and management of the disease in onco-hematological[79] or critically ill patients[1020], although in recent years, attention has shifted towards episodes of candidemia in internal medicine departments[2125].

Data on candidemia in surgical departments are very scarce and only episodes occurring in specific surgical setting have been studied[26]. Furthermore, to our knowledge, candidemia in surgical wards has never been directly compared with episodes in medical wards.

We performed a sub-analysis of the CANDIPOP study in order to describe episodes of candidemia diagnosed in surgical wards, to compare them with episodes occurring in medical wards and to analyze the impact of therapeutic strategies on mortality.

Materials and methods

Patients’ cohort

The findings reported here comprise a sub-analysis of the multicenter Population Study on Candidemia in Spain (CANDIPOP). The period of candidemia surveillance was May 2010 through April 2011 and included all patients who developed an episode of candidemia (regardless of the hospital ward in which the infection occurred) in 29 participating hospitals, located in five of the largest municipal areas of Spain (population 9 498 980, or 20% of the Spanish population). The inclusion criteria, study population, methodology, microbiological studies, and outcomes have been extensively described elsewhere[15, 27]. Briefly, during the study period local laboratories daily identified patients and reported them to study coordinators, who collected data using a standardized case report form. Data included demographic and clinical characteristics, risk factors for candidemia, antifungal management and source control. Thirty-day follow-up outcome was recorded for each patient. Given the observational nature of the study, patients were managed according to routine clinical care.

The local institutional review boards of each participating center (Hospital General Universitario Gregorio Marañón, Madrid; Hospital Universitario La Paz, Madrid; Hospital Universitario Ramón y Cajal, Madrid; Hospital Infanta Leonor, Madrid; Hospital Universitario La Princesa, Madrid; Hospital Universitario del Niño Jesús, Madrid; Hospital Universitario “12 de Octubre,” Madrid; Hospital Clínico San Carlos, Madrid; Fundación Jiménez Díaz, Madrid; Hospital de Alcorcón, Madrid; Hospital Universitario Puerta de Hierro-Majadahonda, Madrid; Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid; Hospital Universitario Virgen Macarena, Sevilla; Hospital Universitario Virgen de Valme, Sevilla; Hospital Universitario Virgen del Rocío, Sevilla; Hospital Quirón Sagrado Corazón, Sevilla; Hospital San Juan de Dios de Aljarafe, Sevilla; Hospital Universitari La Fe, Valencia; Hospital Clínico Universitario de Valencia; Hospital Universitario Dr. Peset, Valencia; Consorcio Hospital General Universitario de Valencia; Hospital de Basurto, Bilbao; Hospital Universitario de Cruces, Bilbao; Hospital de Galdakano, Bilbao; Hospital Universitario Vall d’Hebron, Barcelona; Hospital Clínico IDIBAPS, Barcelona; Hospital Universitario de Sant Pau i Santa Creu, Barcelona; Hospital de Barcelona, Barcelona; Hospital del Mar, Barcelona; Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona) approved this study, and written informed consent was obtained from each patient before enrollment. The IRB of the coordinating center for this study was Comité Ético de Investigación Clínica, Hospital General Universitario Gregorio Marañón.

Definitions

Surgical patients were those admitted to a general or specialist surgical ward when the first blood sample yielding Candida spp. was taken. Medical patients were those admitted to an internal medicine ward or to a subspecialty ward of internal medicine at the time the positive sample was drawn.

Proven catheter-related candidemia was defined according to current guidelines [28], whereas secondary episodes required microbiological documentation of the same Candida species at the onset of the infection[15]. When there were no apparent infections at other sites, candidemia was classed as primary.

We defined initial therapy as the first systemic antifungal drug administered after a positive sample drawn from a peripheral vein. Neutropenia was defined as a neutrophil count ≤500/mm3.

Severity of illness was classified according to the Pitt score[29]. Sepsis, severe sepsis or septic shock were recorded on the day of candidaemia [30]. An episode of candidemia was defined as persistent when patients had positive follow-up blood cultures at least 48 hours after the initiation of antifungal therapy.

In order to assess the impact of therapeutic measures on outcome, antifungal therapy and removal of the central venous catheter (CVC) were evaluated according to previous definitions[15], as follows:

  1. Early antifungal treatment was defined as adequate if a recommended dose of an antifungal drug was administered within 48 hours after candidemia onset and it was found to be effective by in-vitro susceptibility testing.
  2. Early CVC removal was defined as removal of the indwelling catheter within 48 hours after the index blood sample was drawn. In patients who had multiple CVCs, removal of at least the responsible CVC within this timeframe was required.
  3. Early, appropriate management of candidemia was defined as administration of one or more appropriate antifungal drugs (according to in-vitro susceptibility testing) and removal of the CVC within 48 hours of blood sampling. The primary outcome of the study was the 30-day mortality rate.

Data collection

Data were prospectively recorded on a standardized case report form that included demographics, predisposing risk factors within the preceding 30 days, and clinical management. Patients were followed for 30 days and managed according to routine clinical care. No specific recommendations were provided. Laboratories were regularly audited to ensure that all cases were reported.

Microbiological methods

Blood cultures were processed at each participating hospital. Species were identified using routine methods at the local laboratories and Candida isolates were forwarded to the Mycology Reference Laboratory (MRL), National Center for Microbiology (Madrid, Spain), where species identification was confirmed by sequencing the internal transcribed spacer (ITS) regions from ribosomal DNA. ITS1 and ITS2 regions were directly amplified by PCR from yeast suspensions and sequenced using universal primers. Antifungal susceptibility testing was performed according to the EUCAST- method [31]. C. parapsilosis ATCC 22019 and C. krusei ATCC 6258 were used as quality control strains for antifungal drug susceptibility testing.

Statistical analysis

Descriptive statistics were used to summarize the data. Quantitative variables are reported as median and interquartile range (IQR), and categorical variables as counts (%). The chi-square test or Fisher exact tests were used to compare the distribution of categorical variables, including the clinical characteristics of medical and surgical patients and the association between individual risk factors and mortality rate. The t test or Mann-Whitney test was used to compare quantitative variables. Statistical significance was set at p<0.05. Only the first episode of candidemia recorded for an individual patient was considered in the analysis of mortality. The Kaplan-Meier curve was constructed to show the relationship between therapeutic strategies and 30-day survival. Factors that occurred in >10% of patients in the univariate analysis were evaluated in a logistic regression model to test their relationship with mortality. The statistical analyses were performed using Microsoft SPSS PC+, version 15.0 (SPSS, Chicago, Illinois, USA).

Results

During the 1-year study period, a total of 752 episodes of Candida BSI were included in the CANDIPOP study. Of these, 273 (36.3%) were in the ICU, 37 (4.9%) in the emergency department, 36 (4.8%) in hematology wards, 24 (3.2%) pediatric units, and 13 (1.7%) in other wards. The remaining 369 cases (49.1%) occurred in adult patients admitted to either surgical (165 episodes, 21.9%) or medical wards (204 episodes, 27.2%) and are the subject of the present study.

Clinical characteristics of patients admitted to surgical wards

The demographics and clinical features of the 165 patients hospitalized in a surgical ward at the time of their episode are shown in Table 1. Mean age was 65.2 years (range 16–94 years), and 103 patients were men (62%). Most candidemia episodes in surgical wards were diagnosed in a general surgery department (104, 63.0%), followed by urology (13.3%), vascular surgery (7.3%), neurosurgery (5.4%), and traumatology (4.2%).

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Table 1. Comparison of the main demographic and clinical characteristics between patients admitted to surgical and medical wards.

https://doi.org/10.1371/journal.pone.0185339.t001

The most common underlying condition was solid tumor (52.1%) followed by cardiac disease (55 patients, 33.3%). Almost all patients had recently undergone surgery (within the previous 3 months). A CVC was in place in 127 patients (77%), and 94 (57%) were receiving total parenteral nutrition at the time of their episode. The most prevalent source of infection was the CVC (43%); only 9 patients (5.5%) had an abdominal infection. Candidemia was managed early and appropriately within the first 48 hours after blood sample collection in 39.4% of patients. Fluconazole was the preferred therapy in most cases, and 30-day mortality was 15.8%.

Comparison between medical and surgical patients

The main demographic characteristic and risk factors for candidemia in medical and surgical patients are compared in Table 1. Age and sex were similar between groups.

In the surgical wards, candidemia affected significantly more patients with solid tumors (52.1% vs 41.3%, p = 0.04), and significantly fewer with diabetes (16.4% vs 28.9%, p = 0.02), pulmonary disease (18.2% vs 27.0%, p = 0.04), liver disease (15.0% vs 24.0%, p<0.001), neurological disease (16.4% vs 28.9%, p = 0.005), and renal insufficiency (15.8% vs 35.8, p<0.001).

Risk factors for candidemia were also different between the two groups. In the surgical wards, the main factors were surgical intervention (83.6% vs 27.5%, p<0.001), presence of a long term CVC (77% vs 61.8%, p = 0.02), and administration of total parenteral nutrition (57% vs 34.8%, p<0.001); whereas in the medical wards the most frequent factors were previous treatment with corticosteroids (18.8% vs 31.4%, p = 0.004) and other immunosuppressive agents (11.5% vs 30.1%, p<0.001).

Median time to onset of candidemia after admission was significantly longer for surgical patients (26 days) than for medical patients (19 days, p = 0.003). As for source of infection, surgical patients were more likely to have CVC-related candidemia (43% vs 28.4%, p = 0.004) and an intra-abdominal origin (5.5% vs 2%, p = 0.09), whereas medical patients were likely to have candidemia of primary origin (41.8% vs 64.2%, p<0.001). No further significant differences were found between the groups regarding clinical manifestations of the diseases, species distribution, or severity of illness except for the median Pitt score, which was lower in surgical patients than in medical patients (p = 0.004).

In terms of antifungal treatment (Table 2), the only significant difference between the surgical and medical wards was that a higher percentage of medical patients never received an antifungal drug (7.3% vs 15.2%, p = 0.02), because the diagnosis was made peri- or post-mortem.

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Table 2. Therapeutic measures and outcome of patients admitted to medical vs surgical wards.

https://doi.org/10.1371/journal.pone.0185339.t002

Of note, early removal of the CVC and appropriate early management of candidemia were more common in patients in surgical wards than in medical wards (58.2% vs 37.4% [p<0.001] and 39.4% vs 28.4% [p = 0.035], respectively). As for other indicators of quality of care, control blood cultures were more frequently performed in surgical wards (73.3% vs 59.3%. p = 0.035), although the percentage of patients with persistent fungemia did not differ between the groups.

The 30-day mortality rate was 15.8% in the surgical wards and 37.7% in the medical wards (p<0.001).

Outcome and risks factors for mortality

As shown in Table 3, the variables associated with higher 30-day mortality in the univariate analysis were older age, liver disease, previous antifungal therapy, neutropenia, primary source of infection, higher Pitt score, severe sepsis or septic shock at onset and no treatment for candidemia. The variables associated with lower mortality were previous surgery, CVC-related candidemia, azole therapy, early adequate management of candidemia, and admission to a surgical ward.

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Table 3. Univariate analysis of factors associated with 30-day mortality in medical and surgical wards.

https://doi.org/10.1371/journal.pone.0185339.t003

Multivariate analysis (Table 4) showed that the variables associated with mortality were liver disease (OR, 2.68; 95%CI, 1.29–5.55; p = 0.008), neutropenia (OR, 14.80; 95%CI, 1.55–140.98; p = 0.01), higher Pitt score (OR, 1.37; 95%CI, 1.17–1.67; p<0.001), and absence of antifungal therapy (OR, 5.64; 95%CI, 1.94–16.35; p = 0.001). By contrast, the variables that were independently associated with a better outcome were admission to a surgical ward (OR, 0.51; 95%CI, 0.28–0.92; p = 0.03) and appropriate early management of candidemia (OR, 0.27; 95%CI, 0.13–0.55; p = 0.001).

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Table 4. Multivariate logistic regression analysis of prognostic factors associated with 30-day mortality.

https://doi.org/10.1371/journal.pone.0185339.t004

Discussion

Our findings suggest that approximately 50% of episodes of candidemia occur in non-hematological patients and outside the ICU and that patients admitted to surgical wards have a better clinical outcome than those hospitalized in medical wards, mainly because of the lower severity of the underlying disease and, prompt administration of antifungal therapy, and CVC removal.

Candidemia in non-ICU, non-hematological patients has received little attention in the literature. However, in a recent paper by Bassetti et al.[2123, 25], almost 75% of candidemic patients were hospitalized in surgical wards or internal medicine wards. Other studies have reported that 60–75% of episodes occur in non-ICU, non-hematological patients[2123, 25]. Our report, which is one of the largest contemporary epidemiological survey of candidemia, shows that candidemia in non-ICU, non-hematological patients is a major problem, accounting for almost 50% of candidemic episodes diagnosed in Spain. Of those episodes, half occurred in surgical wards and half in internal medicine wards. The circumstances responsible for the high prevalence of candidemia in these "non-classic" settings seem to be multifactorial, including rapid changes in medical practice, ageing of the population, the increasing number of patients with CVC, and the increased number of immunocompromised patients with more complex underlying disease.

Interestingly, when major risk factors for candidemia in adult patients were analyzed[11, 3234], significant differences were observed between surgical and medical patients. Compared with medical cases, surgical patients were much more likely to have undergone a previous surgical intervention or to have a long-term CVC in place at the time of candidemia. On the other hand, medical patients were more likely to have received treatment with corticosteroids and other immunosuppressive agents. These results suggest a different pathogenesis for candidemia between patients admitted to surgical wards and patients admitted to medical wards. Given that the sites most frequently colonized by yeasts are the gastrointestinal tract and skin[35, 36], surgical patients may have acquired fungemia because of rupture of the gastrointestinal barrier during abdominal surgery [37] or due to total parenteral nutrition or skin contamination at vascular insertion sites. Thus, attempts aimed at implementing adequate surgical procedures and optimal CVC care may have a higher impact on reducing episodes of Candida BSI in surgical departments. Conversely, in patients admitted to internal medicine wards, candidemia seems to be related to more frequent immune system dysfunction as a result of therapy with corticosteroids or other immunosuppressive agents. Corticosteroids are known to inhibit neutrophil ingestion and killing of Candida [38] and to promote microorganism translocation [39]. Therefore, since immunosuppressive treatment seems to play a critical role in the development of candidemia in the medical setting, physicians should anticipate the risk of infections and use the lowest possible dose of immunosuppressive drugs for the shortest possible time.

As for the etiology of candidemia, non-hematological patients outside the ICU present the typical distribution of Candida species in our geographical area, where C. albicans is predominant, followed by C. parapsilosis [21, 40], with a low frequency of fluconazole-non-susceptible strains, which in our study was only 4.6%. This finding has important implications for the selection of empirical antifungal therapy among non-hematological candidemic patients hospitalized outside ICUs.

An interesting finding in our study was the lower mortality rate in patients with candidemia hospitalized in surgical wards than in internal medicine wards. The overall mortality in patients with candidemia reported in the literature [2123, 25] ranges from 12.5% to 29.7% for those hospitalized in surgical wards [23, 25], and from 39% to 66% for those hospitalized in internal medicine wards [23, 24]. In our series, overall 30-day mortality was 15.8% and 37.7% in surgical and internal medicine wards, respectively. To date, no in-depth analysis of the prognostic factors of surgical patients with candidemia has been performed.

Our initial hypothesis was that the lower mortality rate associated with candidemia in surgical wards probably reflects differences in the severity of underlying diseases. Indeed, medical patients were sicker and had at least one severe underlying disease such as liver disease, renal failure, and diabetes.

Nonetheless, as recently highlighted in multicenter study by Luzzati et al [41], the difference in outcome could also be related to the low suspicion of fungal infection in medical wards, with a longer time required to confirm a diagnosis. Indeed, prompt antifungal therapy is one the most important factors influencing outcome in candidemia, so even a short delay can be associated with a worse outcome [17, 4244].

Although we do not have sufficient data, it seems that infectious disease specialists, who are more frequently consulted in surgical wards, could also have an impact on the better prognosis of surgical patients. Management of candidemia is clinically challenging, and previous studies showed that involvement of an infectious diseases consultant was associated with better management and even better prognosis [45, 46]. In our series, all indicators of quality of care (ie, follow-up blood sample collection, early antifungal therapy, catheter withdrawal) indicate that more patients in surgical than in medical wards were likely managed with an infectious diseases specialist, thus partially explaining the better prognosis observed in surgical patients. However, more studies are needed to clarify this aspect.

In the present study, we did not observe differences in mortality when echinocandin regimen were administered. Likewise, also other studies of candidemia did not find any association between outcome and treatment with azoles or echinocandins [41, 47], probably reflecting the bias of use echinocandins in the more severely ill patients. Despite this, the percentage of patients hospitalized in internal medicine wards who did not receive antifungal therapy was higher than that of patients admitted to surgical wards (15.2% vs. 7.3%), because blood cultures were observed to be positive late in the disease course. New diagnostic strategies investigating the role of serological biomarkers such as β-D-glucan [48, 49] should be applied in order to identify the medical and surgical patients at the highest risk of candidemia.

Besides adequate antifungal therapy, removal of the CVC within the first 48 hours after onset, is considered the most important determinant of outcome [50, 51]. Consistent with previous findings [43, 52], we also observed that appropriate early management of candidemia (antifungals and CVC removal within 48 hours) was the most important protective factor against mortality and was less commonly present in internal medicine wards. This observation could reflect a bias towards more catheter removal in patients who were less ill. Indeed, compared with patients hospitalized in internal medicine wards, surgical patients had a lower Pitt score and were less frequently affected by other comorbidities. Moreover, it must be acknowledged that CVC as the source of candidemia was more common among patients hospitalized in surgical wards. It has yet to be established whether there is an association between catheter removal and better outcome when the source of candidemia is not the CVC [52]. Although further evidence is needed to resolve this controversial issue, our findings indicate that the CVC should always be removed in medical and surgical patients, even when sources other than the CVC are suspected.

Our study is subject to a series of limitations. First, we did not have data regarding the overall population hospitalized in the internal medicine and surgical wards of the participating hospitals. Consequently, we were not able to calculate the incidence of candidemia in our study populations. Second, although the CANDIPOP study is a multicenter study including a large number of patients, the generalizability of the observations may be limited by differences in Candida epidemiology between geographical areas or by differences in medical practice or health system organization. Nevertheless, these data are important, because they reflect the most significant and robust experience of surgical patients developing candidemia in a large group of centers.

In conclusion, we found that approximately 50% of candidemic episodes occurred in non-hematological patients outside the intensive care unit and that clinical outcome was better in patients admitted to surgical wards than in those hospitalized in medical wards. These findings could be explained by the lower severity of underlying disease, prompt administration of antifungal therapy, and catheter removal.

Acknowledgments

We would like to ackolowedge GEIH-GEMICOMED, Grupo de Estudio de Infección Hospitalaria-Grupo de Estudio de Micología Médica, REIPI, Red Española de Investigación en Patología Infecciosa and SEIMC, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.

Members of the CANDIPOP Project: Belén Padilla, Patricia Muñoz, and Jesús Guinea (Hospital General Universitario Gregorio Marañón, Madrid); José Ramón Paño Pardo, Julio García-Rodríguez, and Carlos García Cerrada (Hospital Universitario La Paz, Madrid); Jesús Fortún, Pilar Martín, and Elia Gómez (Hospital Universitario Ramón y Cajal, Madrid); Pablo Ryan and Carolina Campelo (Hospital Infanta Leonor, Madrid); Ignacio de los Santos Gil and Ventura Buendía (Hospital Universitario La Princesa, Madrid); Beatriz Perez Gorricho and Mercedes Alonso (Hospital Universitario del Niño Jesús, Madrid); Francisca Sanz Sanz and José María Aguado (Hospital Universitario “12 de Octubre,” Madrid); Paloma Merino and Fernando González Romo (Hospital Clínico San Carlos, Madrid); Miguel Gorgolas and Ignacio Gadea (Fundación Jiménez Díaz, Madrid); Juan Emilio Losa and Alberto Delgado-Iribarren (Hospital de Alcorcón, Madrid); Antonio Ramos, Yolanda Romero, and Isabel Sánchez Romero (Hospital Universitario Puerta de Hierro-Majadahonda, Madrid); Oscar Zaragoza and Manuel Cuenca-Estrella (Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid); Jesús Rodriguez-Baño and Ana Isabel Suarez (Hospital Universitario Virgen Macarena, Sevilla); Ana Loza, Ana Isabel Aller García, and Estrella Martín-Mazuelos (Hospital Universitario Virgen de Valme, Sevilla); Maite Ruiz Pérez de Pipaón and José Garnacho (Hospital Universitario Virgen del Rocío, Sevilla); Carlos Ortiz (Hospital Quirón Sagrado Corazón, Sevilla); Mónica Chávez and Fernando L. Maroto (Hospital San Juan de Dios de Aljarafe, Sevilla); Miguel Salavert and Javier Pemán (Hospital Universitari La Fe, Valencia); José Blanquer and David Navarro (Hospital Clínico Universitario de Valencia); Juan José Camarena and Rafael Zaragoza (Hospital Universitario Dr. Peset, Valencia); Vicente Abril and Concepción Gimeno (Consorcio Hospital General Universitario de Valencia); Silvia Hernáez and Guillermo Ezpeleta (Hospital de Basurto, Bilbao); Elena Bereciartua, José L. Hernández Almaraz, and Miguel Montejo (Hospital Universitario de Cruces, Bilbao); Rosa Ana Rivas and Rafael Ayarza (Hospital de Galdakano, Bilbao); Ana Ma Planes, Isabel Ruiz Camps, and Benito Almirante (Hospital Universitario Vall d’Hebron, Barcelona); José Mensa and Manel Almela (Hospital Clínico IDIBAPS, Barcelona); Mercè Gurgui and Ferran Sánchez-Reus (Hospital Universitario de Sant Pau i Santa Creu, Barcelona); Joaquin Martinez-Montauti and Montserrat Sierra (Hospital de Barcelona, Barcelona); Juan Pablo Horcajada, Luisa Sorli, and Julià Gómez (Hospital del Mar, Barcelona); Amadeu Gené and Mireia Urrea (Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona). Study collaborators: Maricela Valerio, Ana Díaz-Martín, Francesc Puchades, and Alessandra Mularoni.

References

  1. 1. Tortorano AM, Kibbler C, Peman J, Bernhardt H, Klingspor L, Grillot R. Candidaemia in Europe: epidemiology and resistance. Int J Antimicrob Agents. 2006;27(5):359–66. Epub 2006/05/02. pmid:16647248.
  2. 2. Wisplinghoff 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(3):309–17. Epub 2004/08/13. pmid:15306996.
  3. 3. Pappas PG, Rex JH, Lee J, Hamill RJ, Larsen RA, Powderly W, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003;37(5):634–43. Epub 2003/08/28. pmid:12942393.
  4. 4. Fridkin SK. Candidemia is costly—plain and simple. Clin Infect Dis. 2005;41(9):1240–1. Epub 2005/10/06. pmid:16206096.
  5. 5. Bassetti M, Righi E, Costa A, Fasce R, Molinari MP, Rosso R, et al. Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis. 2006;6:21. Epub 2006/02/14. pmid:16472387
  6. 6. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198–208. Epub 2014/03/29. pmid:24670166.
  7. 7. Dewan E, Biswas D, Kakati B, Verma SK, Kotwal A, Oberoi A. Epidemiological and mycological characteristics of candidemia in patients with hematological malignancies attending a tertiary-care center in India. Hematol Oncol Stem Cell Ther. 2015. Epub 2015/07/15. pmid:26173033.
  8. 8. Cornely OA, Gachot B, Akan H, Bassetti M, Uzun O, Kibbler C, et al. Epidemiology and Outcome of Fungemia in a Cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031). Clin Infect Dis. 2015;61(3):324–31. Epub 2015/04/15. pmid:25870323.
  9. 9. Gamaletsou MN, Walsh TJ, Zaoutis T, Pagoni M, Kotsopoulou M, Voulgarelis M, et al. A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies. Clin Microbiol Infect. 2014;20(1):O50–7. Epub 2013/07/31. pmid:23889746.
  10. 10. Chakrabarti A, Sood P, Rudramurthy SM, Chen S, Kaur H, Capoor M, et al. Incidence, characteristics and outcome of ICU-acquired candidemia in India. Intensive Care Med. 2015;41(2):285–95. Epub 2014/12/17. pmid:25510301.
  11. 11. Lortholary O, Renaudat C, Sitbon K, Madec Y, Denoeud-Ndam L, Wolff M, et al. Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med. 2014;40(9):1303–12. Epub 2014/08/07. pmid:25097069
  12. 12. Colombo AL, Guimaraes T, Sukienik T, Pasqualotto AC, Andreotti R, Queiroz-Telles F, et al. Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period. Intensive Care Med. 2014;40(10):1489–98. Epub 2014/08/02. pmid:25082359
  13. 13. Bruyere R, Quenot JP, Prin S, Dalle F, Vigneron C, Aho S, et al. Empirical antifungal therapy with an echinocandin in critically-ill patients: prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU. BMC Infect Dis. 2014;14:385. Epub 2014/07/13. pmid:25015848
  14. 14. Meyer E, Geffers C, Gastmeier P, Schwab F. No increase in primary nosocomial candidemia in 682 German intensive care units during 2006 to 2011. Euro Surveill. 2013;18(24). Epub 2013/06/22. pmid:23787164.
  15. 15. Puig-Asensio M, Peman J, Zaragoza R, Garnacho-Montero J, Martin-Mazuelos E, Cuenca-Estrella M, et al. Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med. 2014;42(6):1423–32. Epub 2014/02/22. pmid:24557426.
  16. 16. Kett DH, Azoulay E, Echeverria PM, Vincent JL. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011;39(4):665–70. Epub 2010/12/21. pmid:21169817.
  17. 17. Zilberberg MD, Kollef MH, Arnold H, Labelle A, Micek ST, Kothari S, et al. Inappropriate empiric antifungal therapy for candidemia in the ICU and hospital resource utilization: a retrospective cohort study. BMC Infect Dis. 2010;10:150. Epub 2010/06/08. pmid:20525301
  18. 18. Leroy O, Mira JP, Montravers P, Gangneux JP, Lortholary O. Comparison of albicans vs. non-albicans candidemia in French intensive care units. Crit Care. 2010;14(3):R98. Epub 2010/05/29. pmid:20507569
  19. 19. Bassetti M, Mikulska M, Viscoli C. Bench-to-bedside review: therapeutic management of invasive candidiasis in the intensive care unit. Crit Care. 2010;14(6):244. Epub 2010/12/15. pmid:21144007
  20. 20. Horasan ES, Ersoz G, Goksu M, Otag F, Kurt AO, Karacorlu S, et al. Increase in Candida parapsilosis fungemia in critical care units: a 6-years study. Mycopathologia. 2010;170(4):263–8. Epub 2010/06/05. pmid:20524154.
  21. 21. Bassetti M, Merelli M, Righi E, Diaz-Martin A, Rosello EM, Luzzati R, et al. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol. 2013;51(12):4167–72. Epub 2013/10/11. pmid:24108614
  22. 22. Bassetti M, Taramasso L, Nicco E, Molinari MP, Mussap M, Viscoli C. Epidemiology, species distribution, antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy. PLoS One. 2011;6(9):e24198. Epub 2011/09/22. pmid:21935385
  23. 23. Bassetti M, Merelli M, Ansaldi F, de Florentiis D, Sartor A, Scarparo C, et al. Clinical and therapeutic aspects of candidemia: a five year single centre study. PLoS One. 2015;10(5):e0127534. Epub 2015/05/27. pmid:26010361
  24. 24. De Rosa FG, Corcione S, Filippini C, Raviolo S, Fossati L, Montrucchio C, et al. The effect on mortality of fluconazole or echinocandins treatment in internal medicine wards. PLoS One. 2015;10(5):e0125149. Epub 2015/05/06. pmid:25938486
  25. 25. Bassetti M, Molinari MP, Mussap M, Viscoli C, Righi E. Candidaemia in internal medicine departments: the burden of a rising problem. Clin Microbiol Infect. 2013;19(6):E281–4. Epub 2013/02/19. pmid:23414070.
  26. 26. Pasero D, De Rosa FG, Rana NK, Fossati L, Davi A, Rinaldi M, et al. Candidemia after cardiac surgery in the intensive care unit: an observational study. Interact Cardiovasc Thorac Surg. 2011;12(3):374–8. Epub 2010/12/25. pmid:21183505.
  27. 27. Puig-Asensio M, Padilla B, Garnacho-Montero J, Zaragoza O, Aguado JM, Zaragoza R, et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014;20(4):O245–54. Epub 2013/10/16. pmid:24125548.
  28. 28. Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1–45. Epub 2009/06/06. pmid:19489710
  29. 29. Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, et al. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis. 2004;39(1):31–7. Epub 2004/06/19. pmid:15206050.
  30. 30. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55. 1303622.
  31. 31. Arendrup MC, Cuenca-Estrella M, Lass-Florl C, Hope W. EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST). Clin Microbiol Infect. 2012;18(7):E246–7. Epub 2012/05/09. pmid:22563750.
  32. 32. Arendrup MC, Sulim S, Holm A, Nielsen L, Nielsen SD, Knudsen JD, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol. 2011;49(9):3300–8. Epub 2011/07/01. pmid:21715585
  33. 33. Cleveland AA, Harrison LH, Farley MM, Hollick R, Stein B, Chiller TM, et al. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: results from population-based surveillance. PLoS One. 2015;10(3):e0120452. Epub 2015/03/31. pmid:25822249
  34. 34. Kullberg BJ, Arendrup MC. Invasive Candidiasis. N Engl J Med. 2015;373(15):1445–56. Epub 2015/10/09. pmid:26444731.
  35. 35. Miranda LN, van der Heijden IM, Costa SF, Sousa AP, Sienra RA, Gobara S, et al. Candida colonisation as a source for candidaemia. J Hosp Infect. 2009;72(1):9–16. Epub 2009/03/24. pmid:19303662.
  36. 36. Nucci M, Anaissie E. Revisiting the source of candidemia: skin or gut? Clin Infect Dis. 2001;33(12):1959–67. Epub 2001/11/10. pmid:11702290.
  37. 37. Clancy CJ, Barchiesi F, Falconi DiFrancesco L, Morris AJ, Snydman DR, Yu VL, et al. Clinical manifestations and molecular epidemiology of late recurrent candidemia, and implications for management. Eur J Clin Microbiol Infect Dis. 2000;19(8):585–92. Epub 2000/10/03. pmid:11014620.
  38. 38. Nohmi T, Abe S, Tansho S, Yamaguchi H. Suppression of anti-Candida activity of murine and human neutrophils by glucocorticoids. Microbiol Immunol. 1994;38(12):977–82. Epub 1994/01/01. pmid:7723691.
  39. 39. Alverdy J, Aoys E. The effect of glucocorticoid administration on bacterial translocation. Evidence for an acquired mucosal immunodeficient state. Ann Surg. 1991;214(6):719–23. Epub 1991/12/01. pmid:1741652
  40. 40. Luzzati R, Amalfitano G, Lazzarini L, Soldani F, Bellino S, Solbiati M, et al. Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital. Eur J Clin Microbiol Infect Dis. 2000;19(8):602–7. Epub 2000/10/03. pmid:11014622.
  41. 41. Luzzati R, Merelli M, Ansaldi F, Rosin C, Azzini A, Cavinato S, et al. Nosocomial candidemia in patients admitted to medicine wards compared to other wards: a multicentre study. Infection. 2016;44(6):747–55. pmid:27401690.
  42. 42. Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother. 2005;49(9):3640–5. Epub 2005/08/30. pmid:16127033
  43. 43. Labelle AJ, Micek ST, Roubinian N, Kollef MH. Treatment-related risk factors for hospital mortality in Candida bloodstream infections. Crit Care Med. 2008;36(11):2967–72. Epub 2008/10/01. pmid:18824910.
  44. 44. Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43(1):25–31. Epub 2006/06/08. pmid:16758414.
  45. 45. Takesue Y, Ueda T, Mikamo H, Oda S, Takakura S, Kitagawa Y, et al. Management bundles for candidaemia: the impact of compliance on clinical outcomes. J Antimicrob Chemother. 2015;70(2):587–93. Epub 2014/10/19. pmid:25326087
  46. 46. Antworth A, Collins CD, Kunapuli A, Klein K, Carver P, Gandhi T, et al. Impact of an antimicrobial stewardship program comprehensive care bundle on management of candidemia. Pharmacotherapy. 2013;33(2):137–43. Epub 2013/01/29. pmid:23355283.
  47. 47. Bassetti M, Righi E, Ansaldi F, Merelli M, Trucchi C, De Pascale G, et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med. 2014;40(6):839–45. pmid:24807083.
  48. 48. Cuenca-Estrella M, Verweij PE, Arendrup MC, Arikan-Akdagli S, Bille J, Donnelly JP, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect. 2012;18 Suppl 7:9–18. Epub 2013/01/04. pmid:23137134.
  49. 49. Lamoth F, Cruciani M, Mengoli C, Castagnola E, Lortholary O, Richardson M, et al. beta-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis. 2012;54(5):633–43. Epub 2011/12/27. pmid:22198786.
  50. 50. Puig-Asensio M, Ruiz-Camps I, Fernandez-Ruiz M, Aguado JM, Munoz P, Valerio M, et al. Epidemiology and outcome of candidaemia in patients with oncological and haematological malignancies: results from a population-based surveillance in Spain. Clin Microbiol Infect. 2015;21(5):491 e1–e10. Epub 2015/02/24. pmid:25703212.
  51. 51. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18 Suppl 7:19–37. Epub 2013/01/04. pmid:23137135.
  52. 52. Garnacho-Montero J, Diaz-Martin A, Garcia-Cabrera E, Ruiz Perez de Pipaon M, Hernandez-Caballero C, Lepe-Jimenez JA. Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother. 2013;68(1):206–13. Epub 2012/09/05. pmid:22945914.