The Extended Prevalence of Infection in Intensive Care (EPIC II) study highlighted the importance of infections by Candida species in patients in intensive care units (ICU). In this point prevalence study including critically ill patients in 1265 ICUs worldwide, Candida species were isolated in 17% of all positive cultures,1 and the prevalence of candidemia was 6.87 episodes per 1000 patients admitted to an ICU.2 The prevalence of invasive Candida infections varies with place and time, and methodological differences make it difficult to compare epidemiological reports. Thus, the real prevalence of Candida infections in non-neutropenic critically ill patients is unknown.

Invasive Candida infections are associated with high morbidity and mortality, especially in ICU patients. The crude mortality rate of patients who develop candidemia ranges between 40% and 60%.3–6 A French study found no significant differences in mortality (45.9%) between patients with invasive Candida infections without candidemia and those with candidemia.7 An Italian study found 40.2% overall mortality and pointed out that mortality varied widely with the species causing the infection, from 26.5% for C. parapsilosis to 77.8% for C. tropicalis.8 Nevertheless, underlying disease and comorbidities make it difficult to determine mortality directly attributable to Candida infection. Moreover, early detection and early appropriate treatment have an important impact on mortality.9–11

Although antifungal drugs approved in recent years may improve effectiveness against invasive candidiasis, scientific societies’ recommendations vary widely,12–14 and the best management strategy remains controversial. For this reason, five scientific societies in Spain collaborated in the EPICO Project, program of continued improvement in the quality of care of critically ill patients, in which the Delphi method was used to elaborate consensus guidelines for the diagnosis and treatment of invasive candidiasis in critically ill patients, developing twelve recommendations focused on epidemiology, scores, diagnostic tools, treatment and de-escalation strategies;15 and for the treatment of the invasive candidiasis in critically ill adult patients in special situations, developing 13 recommendations to improve the clinical management of this population in different specific scenarios.16

We aimed to determine whether a multifaceted educational intervention including serious games based on the EPICO Project recommendations could improve physicians’ management of neutropenic or non-neutropenic critically ill adult patients with invasive candidiasis in different scenarios. We hypothesized that the intervention would bring physicians’ attitude and behavior closer in line with the recommendations.

A total of 980 specialists attended the educational sessions of Epico 1; 617 of these had completed the preintervention survey and 276 went on to complete the postintervention survey. Both surveys were completed by 255 specialists, of whom 137 (53.7%) were intensivists, 116 (45.5%) were anesthesiologists, 1 (0.4%) was an internist, and 1 (0.4%) was a cardiologist.

Meanwhile, 551 specialists attended the educational sessions of Epico 2.0; 550 of these completed the preintervention survey and 249 went on to complete the postintervention survey. Both surveys were completed by 248 specialists, of whom 155 (62.5%) were intensivists, 35 (14.1%) were anesthesiologists, 5 (2.0%) were internists, 2 (0.8%) were gastroenterologists, 1 (0.4%) was a microbiologist, and 1 (0.4%) was a pulmonologist. 49 participants (19.8%) did not indicate their specialty.

Tables 1 and 2 summarize the results of the McNemar tests comparing the preintervention and postintervention responses by the specialists who completed both surveys. The preintervention surveys showed that many specialists were unaware of the best approach to manage invasive candidiasis. Specialists’ knowledge and practices after the educational intervention were more in line with nearly all the recommendations specified in the EPICO Project consensus. After the educational intervention of the Epico 1 Study, physicians caring for critically ill patients were more prone to use the Candida Score and biomarkers for early identification of patients, and to obtain blood cultures or intraabdominal specimens in cases of suspected invasive candidiasis. The assessment of antifungal susceptibility in culture reports did also improve. Specialists reported also a shorter time to start of therapy, increased use of echinocandins in unstable patients, more frequent ophthalmic evaluations, and improved source control (central catheter removal). De-escalation from echinocandins to fluconazole also improved after the intervention for infections by C. albicans. The only issues for which the responses did not show a statistically significant shift toward the recommendations were de-escalation from echinocandins to fluconazole in Candida glabrata infections, where a trend (p=0.055) toward increased agreement with the recommendations was observed, and the duration of antifungal treatment in both candidemia and peritoneal candidiasis.

Meanwhile, after the educational intervention of the Epico 2.0 Study, specialists caring for critically ill adult patients in special situations were more prone to initiate antifungal treatment in patients with tertiary peritonitis; administer echinocandins in patients with peritoneal candidiasis with previous exposure to azoles and in neutropenic patients with invasive candidiasis; discontinue the antifungal treatment 14 days following the first negative blood culture; and adjust the dose of azoles in patients with kidney failure without renal replacement therapy. In cases of patients undergoing hemodialysis, a significant shift toward dosage adjustment of all antifungals has been observed. Also, the educational intervention lead to a greater administration of echinocandins–caspofungin, micafungin–in patients with febrile neutropenia and suspected candidemia, and a greater withdrawal of central venous catheter in unstable patients. Finally, a greater tendency of initiating antifungal treatment in peritoneal candidiasis was observed, although it did not reach statistical significance (p=0.09).

As far as we know, this is the first time that multifaceted educational interventions based on previous Delphi recommendations about managing invasive candidiasis in critically ill patients and critically ill adult patients in special situations have been reported. More than a quarter of all ICUs in Spain participated in this study, underlining specialists’ recognition of the importance of invasive candidiasis in critical patients because of its high prevalence and associated morbidity and mortality. Before the EPICO Project, there was no strong consensus on the best approach to managing invasive candidiasis, so it is not surprising that many specialists’ responses on the preintervention survey were not in line with the recommendations specified in the Epico 1 and Epico 2.0 consensus.

After the educational interventions, specialists’ knowledge and practices were more in line with all the recommendations specified by the EPICO Project. However, the intervention was not successful in changing specialist's attitude in de-escalation of echinocandins in C. glabrata infections and treatment duration. Probably, the main reason explaining this lack of change is that the rationale supporting echinocandins de-escalation in this setting could be considered weak by the clinicians and that there is not a specific Epico recommendation for the duration of treatment.

Likewise, no change in the attitude regarding the time elapsed before initiation of treatment in patients with peritoneal candidiasis was observed.

One strength of our intervention was the use of serious games. Despite the evidence about the use of games as an educational strategy to improve health professionals’ performance (e.g. adherence to standards of care) through improving their knowledge, skills and attitudes is controversial,17 some studies have shown promising results to improve the treatment of severe infections.18

Educational programs have been successfully used to improve quality in many areas. Numerous programs in the ICU have achieved gains in both process of care variables and outcomes. Ferrer et al.19 showed that an educational program based on the Surviving Sepsis Campaign guidelines improved compliance with recommendations and reduced mortality in patients with severe sepsis or septic shock in a large group of Spanish ICUs. Another large-scale project carried out in Spanish ICUs, the Bacteremia Zero project, successfully reduced the number of catheter-related bloodstream infections, showing that it is possible to improve the safety culture.20

In a recent systematic review of knowledge translation interventions, Sinuff et al.21 concluded that the most important factors for improving process of care were establishing protocols rather than education per se. To establish useful protocols, the current evidence about best practices needs to be available. In the EPICO Project, a large number of experts in invasive candidiasis used the Delphi method to review the available evidence and reach a consensus about key issues to establish recommendations for the management of invasive candidiasis. These recommendations are a starting point for further studies aimed at improving care for this widespread infection.

Before the EPICO Project, there was no consensus about the best approach to diagnosing and treating invasive candidiasis. The preintervention surveys revealed that specialists involved in treating critical patients with invasive candidiasis often lacked knowledge about important specifics in managing these patients. These multifaceted educational interventions improved participants’ knowledge and attitudes about the management of invasive candidiasis.

EPICO Project Group: List of project coordinators, panel members and attending physicians are listed in the Online material.

EPICO Project Group: List of project coordinators, panel members and attending physicians are listed in the Online material.

These interventions have been sponsored by MSD Laboratories, Spain.