Are prophylactic antifungals in highly colonized patients safe and effective?

Excerpt

The selection of an antifungal regimen is based on multiple factors, including patients’ characteristics, hospital setting, strain of Candida, and site of infection. The most appropriate antifungal regimen can be chosen from three main groups of antifungals: the azoles (mainly fluconazole), the polyenes (lipid formulation of amphotericin B), and the echinocandins (caspofungin, micafungin, anidulafungin). Although different antifungals can show comparable efficacy in treating candidemia and invasive candidiasis, their differences in terms of toxicity, drug–drug interactions, and selection of resistance remain significant and can impact the clinical outcome of fragile patient populations such as the critically ill. Thus, specific guidelines have been created in order to direct the clinicians in the challenging selection of the optimal antifungal therapy [1, 2]. Among patients in the intensive care unit (ICU), crude mortality rates for invasive candidiasis can range from 25 to 60 % [3, 4]. Although risk factors associated with ICU, e.g., use of broad-spectrum antibiotics, intravascular catheters, parenteral nutrition, and high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, are frequently present in patients with candidemia [5], other hospital settings such as the internal medicine wards have shown increasing rates of Candida infections [6]. Candida colonization at one or more deep anatomical sites represents an important risk factor and frequently precedes invasive infections in non-neutropenic patients, and the rate of colonized patients in ICU increases as exposure to risk factors is prolonged [5]. In this regard, Pittet et al. have shown a relationship between the intensity of fungal colonization and the risk of invasive fungal infections (IFI) in ICU patients [7]. Several studies have reported the benefit of antifungal prophylactic therapy in colonized ICU patients to reduce IFI incidence, while many others failed to demonstrate any benefit in the same population [8‐11]. The current study by Ferreira et al. [12] casts more significant doubts whether the extensive use of prophylactic antifungals in highly colonized patients can be considered safe and effective as a routine measure. In their retrospective observational study, the authors demonstrated that Candida colonization-based pre-emptive antifungal prescription of fluconazole and caspofungin generated a significant change in acquired colonization, especially with C. glabrata and C. parapsilosis, without any impact on incidence of candidemia and on Candida-related mortality. Furthermore it led to consumption of fluconazole and caspofungin of up to 240 and 170 DDD/1000 ICU days, respectively, by far higher than those reported usually in ICU [13]. …