Detailed ß-(1→3)-D-glucan and mannan antigen kinetics in patients with candidemia.

Fungal antigens such as ß-(1→3)-D-glucan (BDG) or mannan (Mn) are useful for detection of candidemia. However, detailed data on serum levels before diagnosis and during treatment are scarce. We conducted a prospective study at two German tertiary care centers for 36 months. Sera from adult patients with candidemia were tested for BDG (Fungitell assay) and Mn (Platelia Candida Ag-Plus assay). For each patient, the clinical course and biomarker kinetics were closely followed and compared. 1,243 sera from 131 candidemia episodes and 15 relapses were tested. In 35% of episodes, empirical therapy included an antifungal drug. Before blood culture sampling, BDG and Mn levels were elevated in 62.4% and 30.8% of patients, respectively. Sensitivity at blood culture sampling was 78.6% (BDG) and 35.1% (Mn). BDG levels of non-survivors were significantly higher than those of survivors. During follow-up, a therapeutic response was associated with decreasing BDG and Mn levels in 84.3% or 70.5% of episodes, respectively. A median increase of 513 pg BDG/mL and 390 pg Mn/mL indicated a relapse of candidemia with a sensitivity of 80% or 46.7%, respectively. In 72.9% and 46.8% of patients, increasing BDG or Mn levels were associated with a fatal outcome. Prior to discharge, BDG and Mn levels had dropped or normalized in 65.7% or 82.1% of patients, respectively. Summarising, in patients with candidemia, biomarker positivity usually precedes culture positivity. Relapses are mostly accompanied by secondary biomarker increases. Rising concentrations of BDG and Mn predict lethality, whereas decreasing levels suggest a favorable outcome in the majority of patients.

Comparative Analysis of the Wako ß-Glucan Test and the Fungitell Assay for Diagnosis of Candidemia and Pneumocystis jirovecii Pneumonia.

(1→3)-ß-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 ß-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 Pneumocystis jirovecii 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 (P < 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.

Comparison of (1->3)-ß-D-glucan, mannan/anti-mannan antibodies, and Cand-Tec Candida antigen as serum biomarkers for candidemia.

We 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)-ß-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)-ß-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)-ß-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 Cand-Tec 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)-ß-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)-ß-D-glucan and mannan antigen are the superior biomarkers, depending on whether a sensitivity-driven or specificity-driven approach is used.

Rhino-orbitocerebral zygomycosis caused by Conidiobolus incongruus in an immunocompromised patient in Germany.

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.