Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis

Intensive Care Medicine (Impact Factor: 5.54). 35(1):55-62. DOI: 10.1007/s00134-008-1338-7

ABSTRACT BackgroundInvasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care
unit (ICU).

Objectives and methodsTo review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review
of the literature and a European expert panel discussion.

Results and conclusions
Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific.
One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need
of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive
blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3
β-d glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases
with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult
and is usually based on the evaluation of risk factors.

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    ABSTRACT: Candidaemia and other forms of invasive candidiasis (C/IC) are serious and costly events for hospitalized patients, particularly those in the ICU. Both fluconazole and the echinocandins are recommended as first-line therapy for C/IC. Resource use and cost considerations are important in selecting appropriate treatment but little information is available on the economic implications of using echinocandins in this setting. To compare resource utilization and treatment costs (in $US) associated with the echinocandin anidulafungin (200 mg intravenously on day 1, then 100 mg intravenously daily) versus those of fluconazole (800 mg intravenously on day 1, then 400 mg intravenously daily) as first-line treatment for C/IC. Available charts from patients enrolled in a recent clinical trial comparing anidulafungin and fluconazole for C/IC were reviewed. Patients who were in the ICU at study entry were identified, and the following data, collected during the 13-week study period, were compared between treatment groups: global response at end of study treatment, number of days patients survived after hospital discharge ('hospital-free' days), hospital resource use, and C/IC-related costs (year 2008 values) to a US hospital payer. These comparisons were also conducted for all non-ICU hospitalized patients, and for survivors in both study populations. Sensitivity analyses explored the cost impact of variability in the hospitalization costs between ICUs and non-ICU wards and of reduced duration intravenous therapy. Statistical comparisons between the two treatment groups were conducted for clinical outcomes, resource use and cost measures, using regression models. All statistical comparisons were adjusted for baseline co-variates (Acute Physiology and Chronic Health Evaluation [APACHE] II score, absolute neutrophil count and catheter removal status). For ICU patients with C/IC (n = 63), global response was significantly higher for anidulafungin than fluconazole (68.6% vs 42.9%; p = 0.03). ICU patients treated with anidulafungin had an average of 13.9 more hospital-free days (18.2 vs 4.3 days; p = 0.04) than those treated with fluconazole. After adjustment for co-variates, although lower costs were observed for anidulafungin vs fluconazole in ICU patients and in ICU patients who survived, no statistical differences were found. For all hospitalized patients (n = 159), global response was also higher for anidulafungin (78.3% vs 60.5%; p < 0.01). There was no difference in average length of hospitalization (29.6 days) or hospital-free days. After adjustment for co-variates, anidulafungin treatment resulted in an incremental C/IC-related cost of $US2680 (p = 0.73). For hospitalized patients who survived (anidulafungin 81.9%, fluconazole 69.7%), anidulafungin treatment was associated with an incremental cost of $US231 (p = 0.98). Anidulafungin as first-line treatment of C/IC appears to be of particular benefit to ICU patients, improving clinical outcomes and possibly decreasing costs, driven by reduced ICU and hospital stay, when compared with fluconazole. Anidulafungin also yielded significantly improved treatment outcomes in the general inpatient population, with total costs similar to fluconazole.
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