Diagnostic accuracy of (1→3)-β-D-glucan to predict Pneumocystis jirovecii pneumonia in non-HIV-infected patients

Abstract

Abstract

Objectives: Pneumocystis jirovecii pneumonia (PCP) is a common and potentially fatal opportunistic infection in immunocompromised non-HIV individuals. We have problems with diagnostic protocols for PCP that lack sensitivity and specificity. We designed a retrospective study in which we several methods that are used in diagnostics of PCP. 

Methods: One hundred and eight immunocompromised individuals with typical clinical picture for PCP and suspicious radiological findings were included in the study. Serum samples were taken to measure the values of (1→3)-β-D-glucan (Fungitell, Associates of Cape Cod, USA). Lower respiratory tract samples were obtained to perform direct immunofluorescence (DIF, MERIFLUOR® Pneumocystis, Meridian, USA) stain and real-time PCR (qPCR).

Results: Fifty-four (50%) of the 108 patients in our study had (1→3)-β-D-glucan >500pg/ml.  Patients that have had (1→3)-β-D-glucan concentrations <400 pg/ml in serum, had mean threshold cycles (Ct) 35.43±3.32) versus those that have had (1→3)-β-D-glucan concentrations >400 pg/mL and mean Ct of 28.97±5.27 (P<0.001). The cut-off value for (1→3)-β-D-glucan was set to 496.45 pg/mL and determined PCP with greatest area under the curve value (AUC=0.817, 95% CI: 0.736-0.898, sensitivity=83.3%, specificity=64.6%, p<0.001). Odds ratio (OR) of (1→3)-β-D-glucan to distinguish between colonization and microbiologically proven PCP (DIF positive, qPCR positive) when concentrations of it were >400 pg/mL (62 patients, OR 2.31, 95%CI 1.62-3.27, P<0.001).

Conclusions: Measurement of (1→3)-β-D-glucan or qPCR alone could not be used to diagnose PCP. Diagnostic cut-off value for (1→3)-β-D-glucan >400pg/ml and qPCR Ct of 28.97±5.27, allow identification of true positive PCP with the greatest diagnostic accuracy. Colonization is always possible when levels of (1→3)-β-D-glucan are <400pg/ml and low concentrations of P. jirovecii DNA are detected.

Key words: Pneumocystis jirovecii pneumonia, (1→3)-β-D-glucan, DIF, real-time PCR, colonization with P. jirovecii, non-HIV-infected patients.