A Systematic Review and Meta-analysis of Diagnostic Accuracy of Serum (1-3)-Beta-D-glucan for Pneumocystis Jirovecii Pneumonia Using the Fungitell Assay: Focus on Cutoff Levels

Abstract PurposeWe conducted a meta-analysis to evaluate the diagnostic performance of various levels of serum (1-3)-Beta-D-glucan(BDG) for Pneumocystis jirovecii(PJ) infection using Fungitell assay.MethodsEMBASE, MEDLINE, and the reference lists of relevant studies were identified up to March 12,2021, with no language restrictions. Meta-analysis was performed using random-effects models for bivariate analysis. Subgroup analyses were implemented in HIV-positive Pneumocystis jirovecii pneumonia (PJP), HIV-negative PJP, and PJP versus colonized patients.ResultsNineteen individual studies that included a total of 2,310 participants met our inclusion criteria. The overall sensitivity, specificity, positive likelihood ratio(LR+) and negative likelihood ratio (LR−),and 95 % confidence interval CI of serum-BDG were 0.94(95 % CI: 0.89–0.96),0.76 (95 % CI: 0.65–0.85), 3.99 (95 % CI: 2.59–6.13),0.08 (95 % CI: 0.05–0.15), respectively. Futher stratified analysis of diagnostic values showed that various levels of serum BDG differed in sensitivity, specificity, LR+ and LR− in the diagnosis of PJP. Subgroup analyses also indicated that the cutoff value of 200 pg/mL had sufficient diagnostic accuracy in HIV-positive PJP patients versus controls. Moreover, the 80 pg/mL cutoff value had satisfactory diagnostic accuracy in PJP versus colonized patients, a overall sensitivity of 0.86 (95% CI, 0.73-0.93), a overall specificity of 0.82(95% CI,0.73-0.88), a overall LR+ 4.70(95 % CI: 3.11–7.08), and a overall LR−0.17(95 % CI: 0.09–0.34),individually.ConclusionsThis meta-analysis suggests that the optimal positive threshold for serum BDG, tested by the Fungitell assay, requires better definition and clinical validation rather than the recommended cutoff of 80pg/mL by the manufacturer in the diagnosis of PJP. These cutoff values could be further refined in additional studies that focus on populations that are as homogeneous as possible.