Prospective Evaluation of Serum β-Glucan Testing in Patients With Probable or Proven Fungal Diseases

Abstract

Background. Early diagnosis and treatment are crucial in invasive fungal diseases (IFD). Serum (1-3)-β-d-glucan (BG) is believed to be an early IFD marker, but its diagnostic performance has been ambiguous, with insufficient data regarding sensitivity at the time of IFD diagnosis (TOD) and according to outcome. Whether its clinical utility is equivalent for all types of IFD remains unknown. Methods. We included 143 patients with proven or probable IFD (49 invasive candidiasis, 45 invasive aspergillosis [IA], and 49 rare IFD) and analyzed serum BG (Fungitell) at TOD and during treatment. Results. (1-3)-β-d-glucan was undetectable at TOD in 36% and 48% of patients with candidemia and IA, respectively; there was no correlation between negative BG results at TOD and patients' characteristics, localization of infection, or prior antifungal use. Nevertheless, patients with candidemia due to Candida albicans were more likely to test positive for BG at TOD (odds ratio = 25.4, P = .01) than patients infected with other Candida species. In 70% of the patients with a follow-up, BG negativation occurred in >1 month for candidemia and >3 months for IA. A slower BG decrease in patients with candidemia was associated with deep-seated localizations (P = .04). Thirty-nine percent of patients with rare IFD had undetectable BG at TOD; nonetheless, all patients with chronic subcutaneous IFD tested positive at TOD. Conclusions. Undetectable serum BG does not rule out an early IFD, when the clinical suspicion is high. After IFD diagnostic, kinetics of serum BG are difficult to relate to clinical outcome.

Keywords: (1-3)-β-d-glucan; diagnostic tool; invasive fungal diseases; kinetics.

Figure 1.

Examples of the 4 main categories of (1-3)-β-d-glucan (BG) postdiagnosis kinetic profiles observed after a diagnosis of invasive aspergillosis (IA). For each example, the blue curve represents the BG kinetics before, at the time, and after a diagnosis of IA. The red cross represents the day of collection (D0) of the first biological sample that led to the diagnosis of IA: y-axis, BG values in pg/mL; x-axis, time relative to the day (D0) of collection of the sample that led to the diagnosis of IA, expressed in weeks. (A) Negative BG profile (N = 8 of 37): patients showing persistently negative BG test results after IA diagnosis. The kinetics shown are those of Patient 19 (hematology patient), who received a diagnosis of probable pulmonary IA, for whom 3 BG assays were performed before diagnosis and 6 BG assays were performed within 12 weeks of diagnosis. The first mycological result allowing for the diagnosis of probable IA was the detection of serum galactomannan antigens. (B) Unreliable BG profile (N = 5 of 37): patients showing alternating negative or low BG test results after IA diagnosis. The kinetics shown are those of Patient 2 (hematology patient), who received a diagnosis of probable pulmonary IA, for whom 2 BG assays were performed before diagnosis and 8 BG assays were performed within 16 weeks of diagnosis. The first mycological result allowing for diagnosis of probable IA was the detection of serum galactomannan antigens. (C) Rapid BG decrease profile (N = 6 of 37): patients with positive BG kinetics after IA diagnosis, who showed a rapid decrease in the BG level, with BG negativation in less than 1 month. The kinetics shown are those of Patient 7 (hematology patient), who received a diagnosis of probable pulmonary IA, for whom 2 BG assays were performed before diagnosis and 8 assays were performed within 13 weeks of diagnosis. The first mycological result allowing for diagnosis of probable IA was the detection of serum galactomannan antigens. (D) Slow BG decrease profile (N = 14 of 37): patients with positive BG kinetics after IA diagnosis, who showed persistently elevated BG levels for more than 3 months. The kinetics shown are those of Patient 32 (solid organ transplant), who received a diagnosis of proven multisite IA, for whom 15 BG assays were performed within 33 weeks of diagnosis. The first mycological result allowing for diagnosis of proven IA was a culture of a skin biopsy that tested positive for Aspergillus fumigatus.