Clinical features of patients with candidemia in sepsis

To the Editor: Invasive candidiasis remains a critical problem in intensive care units (ICUs) throughout the developed world.1 Nonetheless, differentiating between those with and without invasive candidiasis among critically ill ICU patients, especially during the early phase of the clinical course, remains challenging. In these situations, it is helpful to be familiar with both the epidemiology of the disease and the typical clinical characteristics of patients with candidemia complicated by sepsis, one of the most common risk factors for candidemia.2 Our aim was to describe the characteristics and clinical features of patients with candidemia admitted to the ICU due to sepsis. This is a case series analysis from a sepsis substudy of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study, a multicenter, prospective cohort study of patients with sepsis. FORECAST was conducted in 59 ICUs from January 2016 to March 2017 in Japan.3 Adult patients (≥16 years) with severe sepsis or septic shock based on Sepsis‐2 criteria and admitted to a participating ICU were included. Among this population, we selected patients with candidemia diagnosed from blood culture results. Of 1184 patients with sepsis, fifteen patients with candidemia were identified (Table 1). Baseline characteristics are shown in Table S1. Six patients died prior to discharge from hospital. Among nine survivors, only one patient was able to return home after discharge (Table S2). The most common species among monomicrobial isolates was C. albicans (six patients). Three of the six patients with C. albicans and three of the nine patients with non–C. albicans died prior to discharge. Catheter‐related blood stream infection (CRBSI) was the most commonly identified source of infection (five patients), followed by lung and abdomen (four patients each). Among five patients with CRBSI, four patients were under 60 years old. All patients with CRBSI survived to discharge, while all patients with fungal pneumonia or empyema died. The incidence of candidemia among patients with sepsis in the FORECAST study 3 was 1.3%, which was comparable with previous studies4 despite significant geographical differences in the Candida species.5 Candidemia should always prompt a search for the source despite the possibility of reflecting colonization of an indwelling intravenous catheter. Our results showed differences in patients with candidemia complicated by sepsis. Deep‐seated infections, which lead to secondary candidemia, were associated with high mortality compared to CRBSI. However, underestimation of patients with candidemia is likely as rates of fungal blood culture positivity are lower than for bacteria. Although there is not yet a magic bullet for the diagnosis of this elusive disease, clinical information, such as comorbidities, need for mechanical ventilation, elevated severity score, and low albumin, remains crucially important in providing clues to the diagnosis of candidemia.1 In conclusion, this is the first report to provide a detailed description of septic patients with candidemia in ICU in Japan. In terms of nosocomial infections, candidemia from deep‐seated sources had poorer outcomes compared to those with candidemia caused by CRBSI. Early recognition of fungal infection remains key.


Clinical features of patients with candidemia in sepsis
To the Editor: Invasive candidiasis remains a critical problem in intensive care units (ICUs) throughout the developed world. 1 Nonetheless, differentiating between those with and without invasive candidiasis among critically ill ICU patients, especially during the early phase of the clinical course, remains challenging. In these situations, it is helpful to be familiar with both the epidemiology of the disease and the typical clinical characteristics of patients with candidemia complicated by sepsis, one of the most common risk factors for candidemia. 2 Our aim was to describe the characteristics and clinical features of patients with candidemia admitted to the ICU due to sepsis. This is a case series analysis from a sepsis substudy of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study, a multicenter, prospective cohort study of patients with sepsis. FORECAST was conducted in 59 ICUs from January 2016 to March 2017 in Japan. 3 Adult patients (≥16 years) with severe sepsis or septic shock based on Sepsis-2 criteria and admitted to a participating ICU were included. Among this population, we selected patients with candidemia diagnosed from blood culture results.
Of 1184 patients with sepsis, fifteen patients with candidemia were identified (Table 1). Baseline characteristics are shown in Table   S1. Six patients died prior to discharge from hospital. Among nine survivors, only one patient was able to return home after discharge (Table S2). The most common species among monomicrobial isolates was C. albicans (six patients). Three of the six patients with C. albicans and three of the nine patients with non-C. albicans died prior to discharge. Catheter-related blood stream infection (CRBSI) was the most commonly identified source of infection (five patients), followed by lung and abdomen (four patients each). Among five patients with CRBSI, four patients were under 60 years old. All patients with CRBSI survived to discharge, while all patients with fungal pneumonia or empyema died.
The incidence of candidemia among patients with sepsis in the FORECAST study 3 was 1.3%, which was comparable with previous studies 4 despite significant geographical differences in the Candida species. 5 Candidemia should always prompt a search for the source despite the possibility of reflecting colonization of an indwelling intravenous catheter. Our results showed differences in patients with candidemia complicated by sepsis. Deep-seated infections, which lead to secondary candidemia, were associated with high mortality compared to CRBSI. However, underestimation of patients with candidemia is likely as rates of fungal blood culture positivity are lower than for bacteria. Although there is not yet a magic bullet for the diagnosis of this elusive disease, clinical information, such as comorbidities, need for mechanical ventilation, elevated severity score, and low albumin, remains crucially important in providing clues to the diagnosis of candidemia. 1 In conclusion, this is the first report to provide a detailed description of septic patients with candidemia in ICU in Japan. In terms of nosocomial infections, candidemia from deep-seated sources had poorer outcomes compared to those with candidemia caused by CRBSI. Early recognition of fungal infection remains key.

ACKNOWLEDG EMENTS
We thank Prof. Gautam Deshpande, MD, for critical comments and English language editing for the first draft. We also thank the JAAM FORECAST Study Group for contribution of this study. JAAM FORECAST Study Group email address: jaam-6@bz04.plala.or.jp.

CO N FLI C T O F I NTE R E S T S
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