Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective studies show that shorter times to treatment are correlated with a lower risk of death. A number of factors can be used to predict which patients would benefit from antifungal prophylaxis or early (pre-emptive or empirical) therapy. Detection of the fungal cell wall component (1→3)-β-D-glucan (BDG) shows promise as an early biomarker of invasive fungal infection and may be useful in identifying patients who would benefit from early antifungal treatment. To date, no consistent early treatment strategy has evolved. Proof-of-concept studies are needed to assess the role of pre-emptive and empirical therapy in ICU patients and the relevance of BDG as an early marker of infection.
"Delays in initiating antifungal therapy may increase mortality rates in patients with candidemia [7, 8]. Consequently, serious attempts have been directed to validating predictive guidelines based on risk factors and/or the presence of fungal biomarkers in order to assist clinicians in their decision to provide early antifungal therapy to patients at high risk [9–12]. "
[Show abstract][Hide abstract] ABSTRACT: PurposeTo describe temporal trends in the epidemiology, clinical management and outcome of candidemia in intensive care unit (ICU) patients.MethodsThis study was a retrospective analysis of 1,392 episodes of candidemia in 647 adult ICU patients from 22 Brazilian hospitals. The characteristics of candidemia in these ICU patients were compared in two periods (2003–2007, period 1; 2008–2012, period 2), and the predictors of 30-day mortality were assessed.ResultsThe proportion of patients who developed candidemia while in the ICU increased from 44 % in period 1 to 50.9 % in period 2 (p = 0.01). Prior exposure to fluconazole before candidemia (22.3 vs. 11.6 %, p < 0.001) and fungemia due to Candida glabrata (13.1 vs. 7.8 %, p = 0.03) were more frequent in period 2, as was the proportion of patients receiving an echinocandin as primary therapy (18.0 vs. 5.9 %, p < 0.001). The 30-day mortality rate decreased from 76.4 % in period 1 to 60.8 % in period 2 (p < 0.001). Predictors of 30-day mortality by multivariate analysis were older age, period 1, treatment with corticosteroids and higher APACHE II score, while treatment with an echinocandin were associated with a higher probability of survival.
ConclusionsWe found a clear change in the epidemiology and clinical management of candidemia in ICU patients over the 9-year period of the study. The use of echinocandins as primary therapy for candidemia appears to be associated with better outcomes.
Intensive Care Medicine 08/2014; 40(10). DOI:10.1007/s00134-014-3400-y · 7.21 Impact Factor
"Potential explanations for the high percentage of patients with prolonged antifungal treatment in our ICU include the difficult diagnosis of invasive fungal disease in ICU patients , and the absence of recommendations on optimal duration of treatment and de-escalation in this population . Prolonged use of antifungals is associated with high hospital cost , and increased risk for fungal resistance . "
[Show abstract][Hide abstract] ABSTRACT: To determine the incidence, risk factors, and impact on outcome of prolonged empirical antifungal treatment in ICU patients.
Retrospective observational study performed during a one-year period. Patients who stayed in the ICU >48 h, and received empirical antifungal treatment were included. Patients with confirmed invasive fungal disease were excluded. Prolonged antifungal treatment was defined as percentage of days in the ICU with antifungals > median percentage in the whole cohort of patients.
Among the 560 patients hospitalized for >48 h, 153 (27%) patients received empirical antifungal treatment and were included in this study. Fluconazole was the most frequently used antifungal (46% of study patients). Median length of ICU stay was 19 days (IQR 8, 34), median duration of antifungal treatment was 8 days (IQR 3, 16), and median percentage of days in the ICU with antifungals was 48% (IQR 25, 80). Seventy-seven patients (50%) received prolonged empirical antifungal treatment. Chemotherapy (OR [95% CI] 2.6 [1.07-6.69], p = 0.034), and suspected infection at ICU admission (3.1 [1.05-9.48], p = 0.041) were independently associated with prolonged empirical antifungal treatment.Duration of mechanical ventilation and ICU stay were significantly shorter in patients with prolonged empirical antifungal treatment compared with those with no prolonged empirical antifungal treatment. However, ICU mortality was similar in the two groups (46 versus 52%, p = 0.62).
Empirical antifungal treatment was prescribed in a large proportion of study patients. Chemotherapy, and suspicion of infection at ICU admission are independently associated with prolonged empirical antifungal treatment.
Annals of Clinical Microbiology and Antimicrobials 03/2014; 13(1):11. DOI:10.1186/1476-0711-13-11 · 2.19 Impact Factor
"Assays that detect fungal cell wall components in the blood of patients with early IFI are commercially available and have been used in Japan for many years. Attractive features of the FungitellTM BDG assay as a screening test are its sensitivity for the detection of early infection , , ,  and high negative predictive value . A few studies have evaluated the utility of serial BDG monitoring in the ICU , , , but none have used biomarker surveillance to inform early treatment decisions. "
[Show abstract][Hide abstract] ABSTRACT: Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.
Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.
Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.
BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.
Clinical Trials.gov NCT00672841.
PLoS ONE 08/2012; 7(8):e42282. DOI:10.1371/journal.pone.0042282 · 3.23 Impact Factor
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