Oral Wash PCR Improves the Diagnosis of Pneumocystis Pneumonia in Immunocompromised Patients Without HIV: A Prospective Multicenter Study.

Abstract

Pneumocystis pneumonia (PCP) is increasingly common in HIV-negative immunocompromised patients, who generally have low fungal burdens. Bronchoalveolar lavage (BAL) may be poorly tolerated in fragile patients, and oropharyngeal wash (OW) could be an interesting alternative, but its effectiveness remains underexplored in these patients. A prospective multicenter cohort study was conducted to assess PCR on OW in HIV-negative patients undergoing BAL to document respiratory symptoms. Beta-1-3-D-glucan (BDG) was also measured on blood samples. Patients were classified by a multidisciplinary committee as having definite PCP, colonization, possible PCP or without Pneumocystis. Positive predictive value (PPV), negative predictive value (NPV) and ROC analysis were determined for each test. Agreement between BAL PCR, OW PCR and BDG was assessed. Statistical analyses were performed on 369 patients: 76 with PCP, 55 colonized, 214 without Pneumocystis, and 24 possible PCP. PCR in OW was positive in 81.6%, 30.9%, 0%, and 45.8% of patients with PCP, colonization, no PCP, and possible PCP, respectively. Mean fungal loads in OW were 4251±15501 and 3±8.5 copies/mL in PCP and colonized patients, respectively (p<0.0001). PPV and NPV of OW PCR were 78.5% and 73.1%, respectively. ROC analysis identified a threshold of 7 copies/mL for OW to achieve a PPV of 90%, with a sensitivity of 73.5%. Agreement between OW PCR and BDG was poor (κ<0.4), but the combination of BDG+/OW PCR+ yielded a PPV of 92%. PCR on OW is a useful non-invasive tool for diagnosing PCP in HIV-negative patients.