Etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in Norway

Jan C Holter, Fredrik Müller, Ola Bjørang, Helvi H Samdal, Jon B Marthinsen, Pål A Jenum, Thor Ueland, Stig S Frøland, Pål Aukrust, Einar Husebye, Lars Heggelund, Jan C Holter, Fredrik Müller, Ola Bjørang, Helvi H Samdal, Jon B Marthinsen, Pål A Jenum, Thor Ueland, Stig S Frøland, Pål Aukrust, Einar Husebye, Lars Heggelund

Abstract

Background: Despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields.

Methods: 267 CAP patients were enrolled consecutively over our 3-year prospective study. Conventional methods (i.e., bacterial cultures, urinary antigen assays, serology) were combined with nasopharyngeal (NP) and oropharyngeal (OP) swab samples analyzed by real-time quantitative PCR (qPCR) for Streptococcus pneumoniae, and by real-time PCR for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis and 12 types of respiratory viruses.

Results: Etiology was established in 167 (63%) patients with 69 (26%) patients having ≥1 copathogen. There were 75 (28%) pure bacterial and 41 (15%) pure viral infections, and 51 (19%) viral-bacterial coinfections, resulting in 126 (47%) patients with bacterial and 92 (34%) patients with viral etiology. S. pneumoniae (30%), influenza (15%) and rhinovirus (12%) were most commonly identified, typically with ≥1 copathogen. During winter and spring, viruses were detected more frequently (45%, P=.01) and usually in combination with bacteria (39%). PCR improved diagnostic yield by 8% in 64 cases with complete sampling (and by 15% in all patients); 5% for detection of bacteria; 19% for viruses (P=.04); and 16% for detection of ≥1 copathogen. Etiology was established in 79% of 43 antibiotic-naive patients with complete sampling. S. pneumoniae qPCR positive rate was significantly higher for OP swab compared to NP swab (P<.001). Positive rates for serology were significantly higher than for real-time PCR in detecting B. pertussis (P=.001) and influenza viruses (P<.001).

Conclusions: Etiology could be established in 4 out of 5 CAP patients with the aid of PCR, particularly in diagnosing viral infections. S. pneumoniae and viruses were most frequently identified, usually with copathogens. Viral-bacterial coinfections were more common than pure infections during winter and spring; a finding we consider important in the proper management of CAP. When swabbing for qPCR detection of S. pneumoniae in adult CAP, OP appeared superior to NP, but this finding needs further confirmation.

Trial registration: ClinicalTrials.gov Identifier: NCT01563315 .

Figures

Figure 1
Figure 1
Study flowchart.aThirty-three patients were excluded due to no findings of new infiltrate (n = 19); chest radiograph was not performed (n = 1); fever was not documented (n = 4); noninfectious cause and/or bronchial obstruction (n = 7); or previous discharge from hospital within the last 14 days (n = 2). bOf these, 43 patients had not received antibiotics prior to hospital admission. Abbreviations: ID, identification; CRF, case record form.
Figure 2
Figure 2
Diagnostic yields of different microbiological methods. Bars are percentages of cases with a positive test relative to the number of cases with a valid test, n (numbers inside the bars). Sputum culture: good-quality sputum by microscopy. A: Detection of bacteria and viruses, regardless of detection spectrum. B: Detection of S. pneumoniae and influenza viruses. OP, oropharynx; NP, nasopharynx; S. pneumoniae, Streptococcus pneumoniae; BAL, bronchoalveolar lavage; PCR, polymerase chain reaction.
Figure 3
Figure 3
Microbial findings in 64 cases with complete sampling and the proportion of coinfections.S. pneumoniae, Streptococcus pneumoniae; H. influenzae, Haemophilus influenzae; B. pertussis, Bordetella pertussis; C. pneumoniae, Chlamydophila pneumoniae; M. pneumoniae, Mycoplasma pneumoniae; M. catarrhalis, Moraxella catarrhalis; H. parainfluenzae, Haemophilus parainfluenzae.
Figure 4
Figure 4
Seasonal variations of microbial findings in patients with CAP during a 3-year period. A: Monthly distribution of viral findings. Each segment in the stacked bars represents the proportion of cases with a positive test relative to those with a valid test for detection of a specific virus. At least one test (PCR or serology) was demanded for a valid detection of influenza viruses (n = 266), whereas only PCR for all other viruses (n = 243). Continuous line shows the proportion of cases with a positive test of any virus relative to those with a valid test for the complete detection of viruses (n = 231). B: Pure bacterial, pure viral and viral–bacterial findings in a subset of 64 patients with complete samples collected. RSV, Respiratory syncytial virus; CAP, community-acquired pneumonia.

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