Combination of serum and peritoneal 1.3-beta-D-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study

Abstract

Background: Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC.

Methods: This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako^® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell^® beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements.

Results: Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%.

Conclusion: In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure.

Trial registration: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Keywords: Beta-D-glucan; Candida; Critically ill patient; Diagnostic; Intra-abdominal candidiasis.

Fig. 1

Study design and inclusion criteria. Abbreviations: BDG: 1.3 beta-d-glucan; IAC: intra-abdominal infection; IAI: intra-abdominal infection. Risk factors according to [–22], Peritonitis score according to [23]

Fig. 2

Flow chart of the study

Fig. 3

Serum and peritoneal 1.3 beta-d-glucan concentrations in IAC patients versus non-IAC. A Box and whiskers with median, 10 and 90% percentile of peritoneal BDG between confirmed IAC and non-IAC patients (Wako^® beta-glucan test, Fujifilm Wako Chemicals Europe, Neuss, Germany). Dotted line represents the threshold of 45 pg/ml. B Box and whiskers with median, 10 and 90% percentile of serum BDG measured with the Wako^® beta-glucan test (Fujifilm Wako Chemicals Europe, Neuss, Germany) at Day 1 between confirmed IAC and non-IAC patients. Dotted line represents the threshold of 3.3 pg/ml (WT). C Box and whiskers with median, 10 and 90% percentile of serum BDG measured with the Fungitell^® beta-d-glucan assay (FA, Associate of Cape Cod, East Falmouth, Inc., United States of America) at Day 1 between confirmed IAC and non-IAC patients. Dotted line represents the threshold of 80 pg/ml (FA). Abbreviations: IAC: intra-abdominal candidiasis; BDG: 1.3 beta-d-glucan; WT: Wako^® beta-glucan test (Fujifilm Wako Chemicals Europe, Neuss, Germany); FA: Fungitell^® beta- d-glucan assay (Associate of Cape Cod, East Falmouth, Inc., United States of America)

Fig. 4

Peritoneal and serum 1.3 beta-d-glucan to rule out intra-abdominal candidiasis in secondary peritonitis. Receiver operating characteristic curve of peritoneal and serum 1.3 beta-d-glucan for identification of intra-abdominal candidiasis (A—peritoneal BDG (n = 196)/B—serum BDG at Day 1 according to the test used (Wako test^® N = 42 and Fungitell^® beta-d-glucan assay N = 140). Abbreviations: FA: Fungitell^® beta-d-glucan assay (Associate of Cape Cod, East Falmouth, Inc., United States of America); pBDG: peritoneal 1.3 beta-d-glucan; sBDG: serum 1.3 beta-d-glucan; WT: Wako^® beta-glucan test (Fujifilm Wako Chemicals Europe, Neuss, Germany)