Quantitative PCR to diagnose Pneumocystis pneumonia in immunocompromised non-HIV patients

• Published in: The European respiratory journal Vol. 39; no. 4; pp. 971 - 978
• Main Authors: MÜHLETHALER, K, BÖGLI-STUBER, K, WASMER, S, VON GARNIER, C, DUMONT, P, RAUCH, A, MÜHLEMANN, K, GARZONI, C
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.04.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Biological and medical sciences; Bronchoalveolar Lavage Fluid; Female; Human viral diseases; Humans; Immunocompromised Host; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Opportunistic Infections - diagnosis; Opportunistic Infections - immunology; Opportunistic Infections - microbiology; Pneumocystis; Pneumocystis carinii - genetics; Pneumocystis carinii - growth & development; Pneumocystis carinii - isolation & purification; Pneumology; Pneumonia, Pneumocystis - diagnosis; Pneumonia, Pneumocystis - immunology; Pneumonia, Pneumocystis - microbiology; Real-Time Polymerase Chain Reaction - methods; Respiratory system : syndromes and miscellaneous diseases; Retrospective Studies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Pneumonia; quantitative PCR; immunocompromised; HIV negative; Pneumocystis pneumonia; Fungi; Fungi Imperfecti; Diagnosis; Quantitative analysis; Pneumology; Immunopathology; Lung disease; Respiratory disease; Retroviridae; AIDS; Lentivirus; Immune deficiency; molecular diagnosis; Infection; Virus; Polymerase chain reaction; Viral disease; Pneumocystis; Human immunodeficiency virus; Molecular biology; Pneumocystis jirovecii
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00095811

The utility of quantitative Pneumocystis jirovecii PCR in clinical routine for diagnosing Pneumocystis pneumonia (PCP) in immunocompromised non-HIV patients is unknown. We analysed bronchoalveolar lavage fluid with real-time quantitative P. jirovecii PCR in 71 cases with definitive PCP defined by positive immunofluorescence (IF) tests and in 171 randomly selected patients with acute lung disease. In those patients, possible PCP cases were identified by using a novel standardised PCP probability algorithm and chart review. PCR performance was compared with IF testing, clinical judgment and the PCP probability algorithm. Quantitative P. jirovecii PCR values >1,450 pathogens·mL(-1) had a positive predictive value of 98.0% (95% CI 89.6-100.0%) for diagnosing definitive PCP. PCR values of between 1 and 1,450 pathogens·mL(-1) were associated with both colonisation and infection; thus, a cut-off between the two conditions could not be identified and diagnosis of PCP in this setting relied on IF and clinical assessment. Clinical PCP could be ruled out in 99.3% of 153 patients with negative PCR results. Quantitative PCR is useful for diagnosing PCP and is complementary to IF. PCR values of >1,450 pathogens·mL(-1) allow reliable diagnosis, whereas negative PCR results virtually exclude PCP. Intermediate values require additional clinical assessment and IF testing. On the basis of our data and for economic and logistical limitations, we propose a clinical algorithm in which IF remains the preferred first test in most cases, followed by PCR in those patients with a negative IF and strong clinical suspicion for PCP.