(1→3)-β-d-Glucan (BDG) is a biomarker for invasive fungal disease. Until now, all BDG data in the Western Hemisphere were obtained using the Fungitell assay (FA). How it compares to the Wako β-glucan test (GT), which was recently launched in Europe, is largely unknown. We conducted a case-control study to compare the two assays in serum samples from 120 candidemia and 63 pneumonia (PCP) patients. Two hundred patients with bacteremia or negative blood cultures served as candidemia control group. In patients with candidemia the median BDG values of the FA and the GT were 351 and 8.4 pg/ml, respectively. With both assays, the BDG levels in candidemia were significantly higher than those measured in the control group ( < 0.001). The sensitivity, specificity, and positive and negative predictive values for the diagnosis of candidemia were 86.7%, 85.0%, 6.0%, and 99.8% for the FA and 42.5%, 98.0%, 19.0%, and 99.4% for the GT, respectively. In PCP patients the median BDG values of the FA and the GT were 963 and 57.7 pg/ml, respectively. The sensitivities for PCP diagnosis were 100% for the FA and 88.9% for the GT. In practical terms, the GT proved to be robust and applicable for testing single samples, whereas for economic reasons the FA required the samples to be tested in batch. The sensitivity of the FA is superior to that of the GT. However, the GT is a valuable alternative to the FA, especially for patients with suspected PCP and in laboratories with low sample throughput.

bWe conducted a case-control study using the Fungitell assay, the novel Platelia Candida Antigen (Ag) Plus and Candida Antibody (Ab) Plus assays, and the Cand-Tec latex agglutination test to evaluate the usefulness of (1¡3)-␤-D-glucan (BDG), mannan antigen with/without anti-mannan antibody, and Cand-Tec Candida antigen measurement for the diagnosis of candidemia. A total of 56 patients fulfilled the inclusion criteria and were enrolled. One hundred patients with bacteremia and 100 patients with sterile blood cultures served as negative controls. In the candidemia group, median (1¡3)-␤-D-glucan, mannan antigen, and anti-mannan antibody levels were 427 pg/ml, 190 pg/ml, and 18.6 antibody units (AU)/ml, respectively. All three parameters were significantly elevated in patients with candidemia. The sensitivity and specificity were, respectively, 87.5% and 85.5% for (1¡3)-␤-D-glucan, 58.9% and 97.5% for mannan antigen, 62.5% and 65.0% for anti-mannan antibody, 89.3% and 63.0% for mannan antigen plus anti-mannan antibody, 89.3% and 85.0% for BDG plus mannan antigen, and 13.0% and 93.9% for CandTec Candida antigen. The low mannan antigen sensitivity was in part caused by Candida parapsilosis and Candida guilliermondii fungemias, which were not detected by the Platelia Candida Ag Plus assay. When the cutoff was lowered from 125 pg/ml to 50 pg/ml, mannan antigen sensitivity increased to 69.6% without severely affecting the specificity (93.5%). Contrary to recently published data, superficial candidiasis was not associated with elevated mannan antigen levels, not even after the cutoff was lowered. Combining procalcitonin (PCT) with (1¡3)-␤-D-glucan to increase specificity provided a limited advantage because the benefit of the combination did not outweigh the loss of sensitivity. Our results demonstrate that the Cand-Tec Candida antigen and the mannan antigen plus anti-mannan antibody measurements have unacceptably low sensitivity or specificity. Of the four tests compared, (1¡3)-␤-D-glucan and mannan antigen are the superior biomarkers, depending on whether a sensitivity-driven or specificity-driven approach is used.

Mucorales (subphylum Mucoromycotina) are well-known agents of invasive mucormycosis, whereas Entomophthorales (subphylum Entomophthoromycotina) are rarely encountered in human diseases in temperate zones. Here we report a fatal case of invasive rhino-orbitocerebral entomophthoramycosis caused by Conidiobolus incongruus in a 78-year-old woman with myelodysplastic syndrome. CASE REPORTA 78-year-old woman with known hypoplastic myelodysplastic syndrome (MDS) with trilinear pancytopenia was admitted to our hospital for further evaluation and treatment of refractory fever. Two months earlier she had been diagnosed with hypoplastic MDS without cytogenetic alterations. Because of her good clinical presentation and her age, chemotherapy was not initiated. Other known comorbidities were arterial hypertension and non-insulin-dependent diabetes mellitus without signs of hyperglycemia. Five weeks before admission, she had developed cellulitis on the right side of the forehead and treatment with cefuroxime intravenously (i.v.) (3 doses of 1.5 g/day) had been initiated, because of an initial swab from which methicillin-sensitive Staphylococcus aureus was cultured. At the time of referral, the patient was in a reduced general state of health and she was unable to open the right eye. Hemogram showed leukocyte counts of 700/l, a hemoglobin level of 6.9 g/dl, thrombocyte counts of 2,000/l, and a C-reactive protein level of 476 mg/liter. Blood cultures remained sterile. Galactomannan and (133)-beta-D-glucan detection in serum was attempted repeatedly with negative results. However, fever persisted and antibiotic therapy was switched to piperacillintazobactam i.v. (3 doses of 4.5 g/day) and finally to imipenem i.v. (3 doses of 1 g/day). Trimethoprim-sulfamethoxazole orally (p.o.) (2 doses of 960 mg twice per week) was given regularly as anti-Pneumocystis jirovecii prophylaxis, and fluconazole (1 dose of 200 mg/day p.o.) was given as antimycotic prophylaxis. Supportive therapy with granulocyte colony-stimulating factor and transfusion of erythrocytes and thrombocytes were started, but cellulitis progressed. A computed tomography (CT) scan of the skull and midface showed frontal hypodensity, suggestive of intracerebral abscess formation; signs of pansinusitis; and periorbital edema with orbital inflammation (Fig. 1A). Sinus surgery was performed. Samples of all affected bones were sent for microbiological and pathological examination. Anti-infective therapy was changed to levofloxacin i.v. (1 dose of 500 mg/day) and liposomal amphotericin B i.v. (1 dose of 200 mg/day). Histological examination of the ethmoidal cells revealed a chronic inflammatory infiltrate containing lymphocytes, plasma cells, and a few dispersed granulocytes. Hyphae with almost orthogonal branches, which invaded the mucosal stroma, were seen (Fig. 1B). Invasion into the bones or vascular structures could not be verified. No signs of SplendoreHoeppli phenomenon were found.Direct fluorescence microscopy using calcofluor white (fluorescent fungal cell wall stain; Bay...