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

Abstract

Background Pneumocystis jirovecii pneumonia (PCP) is a common and potentially fatal opportunistic infection in immunocompromised non-HIV individuals. There are problems with clinical and diagnostic protocols for PCP that lack sensitivity and specificity. We designed a retrospective study to compared several methods that were used in diagnostics of PCP. Patients and 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 > 500 pg/ml. Patients that had (1→3)-β-D-glucan concentrations < 400 pg/ml in serum, had mean threshold cycles (Ct) 35.43 ± 3.32 versus those that had (1→3)-β-D-glucan concentrations >400 pg/mL and mean Ct of 28.97 ± 5.27 (P < 0.001). If we detected P. jirovecii with DIF and qPCR than PCP was proven. If the concentration of (1→3)-β-D-glucan was higher than 400 pg/ml and Ct of qPCR was below 28.97 ± 5.27 than we have been able be certain that P. jirovecii caused pneumonia (odds ratio [OR] 2.31, 95% confidence interval [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 below 30 Ct, allow us to conclude that patient has PCP. If the values of (1→3)-β-D-glucan are < 400 pg/ml and qPCR is above 35 Ct than colonization with P. jirovecii is more possible than PCP.

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