COMMENT|ONLINE FIRST
Guidelines adherence as a major protective aspect to increase survival rate in patients with candidaemia in Europe
Mohammad Sadegh Rezai, Fatemeh Ahangarkani
Lancet Infect Dis Published:February 15, 2023
DOI:https://doi.org/10.1016/S1473-3099(23)00046-4
Despite improvements in medical interventions and new antifungal drugs, candidaemiais widely recognised as a major cause of morbidity and mortality worldwide.1, 2 Notably, the shift from typical candidaemia due to Candida albicans towards candidaemia caused by various other Candida spp is associated with increased mortality and reduced susceptibility to antifungal drugs.3 Recommendations for diagnosing and managing candidaemia can be found in the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the Infectious Diseases Society of America (IDSA) guidelines.4, 5
In a multicentre study published in The Lancet Infectious Diseases, Martin Hoenigl and colleagues6 provide data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to candidaemia guideline recommendations is associated with outcomes. The authors assessed adherence to the ESCMID and the IDSA guidelines using the European Confederation of Medical Mycology Quality of Clinical Candidaemia Management (EQUAL Candida) score.6 Higher EQUAL Candida scores reflect increased adherence to clinical guideline suggestions.7
The study included 632 patients with candidaemia from 64 institutions in 20 European countries recruited after July 1, 2018. The majority of patients (58%) were male, and the median age was 65 years (IQR 53–73). The most common underlying conditions were haematological or oncological malignancy (39% of patients), intensive care unit (ICU) admission (37%), and recent major surgery (26%). Catheter-related candidaemia was observed in 21% of patients. Echocardiography was done in 35% of patients, showing cardiac involvement in 11%, whereas ophthalmoscopy was done in 27% of patients, showing ocular involvement in 11%. C albicans (46%), C glabrata (21%), C parapsilosis (13%), and C tropicalis (7%) were the most commonly isolated Candida spp. Emerging Candidaspp were less common (eg, C auris in 3% of patients). Initial echinocandin treatment was the first-line antifungal treatment in 56% of patients, and step-down therapy to fluconazole was given to 29% of patients. The all-cause (overall) mortality was 46%, of which 37% was attributable to candidaemia, and the overall 90-day mortality was 43%.
Hoenigl and colleagues6 reported that the EQUAL Candida scores were associated with the duration of hospital stay (p<0·0001), and even after excluding patients hospitalised for 7 days or less, the EQUAL Candida scores were higher in survivors than in non-survivors (p<0·0001). In the Cox regression analysis, increasing age, ICU admission, point increases in the Charlson comorbidity index score, and C tropicalis as causative pathogenwere independent baseline predictors of mortality.
Moreover, after adjusting for the baseline predictors in the multivariable Cox regressionanalyses, the EQUAL Candida score remained an independent predictor of mortality. The authors stated that mortality in patients for whom guideline-recommended diagnostic or therapeutic measures were not performed was higher (51–71%) than mortality in the overall cohort (46%). In the multivariable Cox model comparing the effect of guideline-recommended diagnostic or therapeutic measures for patients who survived for more than 7 days and adjusted for the baseline predictors, the following not-performed or not-completed measures were predictors of mortality: ophthalmoscopy, echocardiography, treatment for 14 days or more after the first negative blood culture, and step-down therapy to fluconazole.6
Hoenigl and colleagues comprehensively described how adherence to guidelines might be promising for the survival of patients with candidaemia. The authors found that initial echinocandin treatment was associated with reduced overall mortality and increased hospital stay among survivors despite the possibility of associated risks, such as hospital-acquired infections and increased costs. Notably, although treatment with echinocandins in patients with candidaemia has higher efficacy than treatment with other antifungals,8the emergence of pan-echinocandin-resistant Candida spp should be considered.9Additionally, in some situations, echinocandins are not an appropriate treatment option for the empirical treatment of candidaemia. For example, in patients in whom candidaemia has a renal origin, fluconazole is preferable to other antifungal drugs, whereas in cases of suspected fungal infection and absence of microbiological diagnosis results (due to the lack of access to appropriate laboratory facilities and equipment in low-income countries10), broad-spectrum antifungals should be used instead of echinocandins.
The importance of the study by Hoenigl and colleagues originates from several factors. First, the study, which was done on a large scale across Europe, showed that overall 90-day mortality was high in European countries, suggesting that candidemia remains a medical emergency. Second, the study clearly showed the importance of individual, guideline-recommended diagnostic and therapeutic measures in the successful management of candidaemia. Finally, Hoenigl and colleagues showed the promising role of adherence to guidelines in increasing survival in patients with candidaemia in Europe.
