Diagnostic-driven antifungal approach in neutropenic patients at high risk for chronic disseminated candidiasis: preliminary observations on the role of 1,3-beta-D-glucan antigenemia and multiphasic contrast-enhanced computed tomography

Chronic disseminated candidiasis (CDC) is a critical form of invasive fungal infection (IFI) that affects mainly the liver, spleen, and, occasionally, kidneys [1]. Typical clinical, microbiological, and/or radiological manifestations have late onset, leading frequently to misdiagnosis [1, 2]. A late diagnosis leads to a delay in starting an effective antifungal therapy against Candida infection resulting in a severe morbidity and high mortality [3]. Recent studies have shown effective alternatives to traditional microbiological and radiological procedures for the diagnosis of CDC, in particular, 1,3-?-Dglucan (BDG) antigenemia and contrast-enhanced computed tomography (CE-CT) [4, 5]. The preemptive approach, based on the routine surveillance with serum BDG and hepatosplenic CE-CT, has been proposed for obtaining a reliable and early diagnosis of CDC, and for establishing a proper antifungal treatment [6]. However, guidelines give moderate evidence to support recommendation for the use of such approach in clinical practice [7]. In our institution, patients with acute leukemia at high-risk for CDC underwent diagnosticdriven approach, which was based on the identification of the clinical settings requiring intensive diagnostic efforts. Between January 2013 and December 2014, 20 of 24 consecutive patients older than 18 years with several risk factors for Candida infection (and on fluconazole prophylaxis), who underwent intensive chemotherapy or autologous stem cell transplantation (SCT), developed febrile neutropenia (FN). In the event of FN, a standard diagnostic work-up (SDWU) was performed as already reported [8]. Patients with persisting fever after 4-6 days of broad-spectrum antibiotics or patients with fever relapsing after 48 h of defervescence underwent a baseline diagnostic work-up (BDWU) including serum BDG antigenemia (Fungitell, manufacturer; Associated of Cape Cod, Inc., East Falmouth, MA). An intensive diagnostic work-up (IDWU) was performed in patients with a positive BDG test (>= 80 pg/mL). It included multiphasic CE helical CT of the liver and spleen, as already described [9]. Among this series of 24 patients, we report a patient suffering from CDC, which was definitively proven by ultrasonography (US)-guided core needle cutting biopsy (CNCB) of the liver. The most important aspect, revealed by the clinical case herein described, is the crucial role of the serum BDG test and the hepatosplenic multiphasic CE helical CT for the early diagnosis of deep-seated Candida infection.