Pseudomonas aeruginosaas a Cause of 1,3‐β‐d‐Glucan Assay Reactivity

To the Editor—The fungal component 1,3-β-d-glucan is increasingly used to diagnose invasive fungal infection in immunocompromised patients [1]. Some studies showed false-positive results (i.e., positive findings not related to invasive fungal infection) in bacteremic patients, which were not related to known causes of reactivity, such as 1,3-β-d-glucan in fungal-derived antibiotics [1–4]. We also observed 1,3-β-d-glucan reactivity in tests (Fungitell; Associates of Cape Cod) of plasma samples obtained from bacteremic patients. For 2 (22%) of 9 hematology patients with Pseudomonas bacteremia and 1 (20%) of 5 patients with Streptococcus pneumoniae bacteremia, 1,3-β-d-glucan reactivity (i.e., the 1,3-β-d-glucan level of the plasma samples is higher than the cutoff value of 80 pg/mL) was found in plasma that was obtained on the same day that the blood culture specimen was taken. All known causes of 1,3-β-d-glucan reactivity were ruled out in these patients, including the presence of invasive fungal disease or treatment with glucan-containing antibiotics. We then determined 1,3-β-d-glucan reactivity of different bacteria, including those that are commonly isolated from the blood of immunocompromised patients (figure 1). No reactivity was observed for most of the clinical isolates tested. However, in addition to Alcaligenes faecalis and S. pneumoniae, which are known to produce 1,3-β-d-glucan [2], we found that Pseudomonas aeruginosa also showed 1,3-β-d-glucan reactivity. The reactivity in the supernatant of all 7 P. aeruginosa cultures increased during growth and decreased after treatment with 1,3-β-d-glucanase, demonstrating the specificity of the reaction. Although a recent study showed the presence of osmoregulated periplasmic 1,2-β-glucan and 1,6-β-glucan in P. aeruginosa [5], this is the first study that suggests the presence of 1,3-β-d-glucan in this bacterial species. The 1,3-β-d-glucan reactivity of different bacteria and other strains. The reactivity of several bacterial culture supernatants was tested with the Fungitell assay (Associates of Cape Cod) in accordance with the manufacturer's instructions. Bacteria, including those isolated from cultures of blood from immunocompromised patients and those isolated from human gut, were cultured in human serum from healthy donors supplemented with glucose (100 mmol/L) for 72 h at 120 rpm and 37°C. All isolates were tested at least twice in duplicate. Bacterial strains are clinical isolates from the Radboud University Nijmegen Medical Center collection. In addition, Pseudomonas aeruginosa American Type Culture Collection 10145 was tested. Alcaligenes faecalis was used as a positive control, and culture medium was used as a negative control. Our findings suggest that the Fungitell assay cross-reacts with bacterial 1,3-β-d-glucans of P. aeruginosa and that this might result in positive test results in patients with bacteremia due to this bacteria. Because the Fungitell assay is increasingly used to diagnose invasive fungal infection in immunocompromised patients, it is important for physicians to be aware of the potential cross-reactivity with P. aeruginosa, which are bacteria that can cause rapidly lethal infection in this patient group. Potential conflicts of interest. All authors: no conflicts.