Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study

Abstract

Background: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents.

Methods: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated.

Results: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP.

Conclusions: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Keywords: Aetiology; Community-acquired pneumonia; Priority screening pathogens; Risk factor; Severe infection.

Fig. 1

Pathogen detection among Chinese adults with community-acquired pneumonia requiring hospitalization, 2014–2019. The dark shade represents single detection, while the light shade represents co-detection. IFVs, influenza viruses (A, B and C); EVs, enteroviruses; HRVs, human rhinoviruses; HCoVs, human coronaviruses; HPIVs, parainfluenza viruses; Adv, adenovirus; RSV, respiratory syncytial virus; HMPV, human metapneumovirus; HBoV, human bocavirus; HPeV, human parechovirus; M. pneumoniae, Mycoplasma pneumoniae; K. pneumoniae, Klebsiella pneumoniae; H. influenzae, Haemophilus influenzae; S. pneumoniae, Streptococcus pneumoniae; S. aureus, Staphylococcus aureus; M. catarrhalis, Moraxella catarrhalis; P. jirovecii, Pneumocystis jirovecii; C. pneumonia, Chlamydia pneumoniae; L. pneumophila, Legionella pneumophila/Legionella longbeachae; Bordetella spp., Bordetella species (except for Bordetella parapertussis); Salmonella spp., Salmonella species

Fig. 2

Age distribution of community-acquired pneumonia patients infected with respiratory pathogens. (A) The detection rate of viruses and bacteria in different age groups. (B) Positive detection of bacteria in different age groups. (C) Positive detection of viruses in different age groups. The green bar indicates single bacterium detection, the orange bar indicates single virus detection, and the dark green bar indicates co-detection of bacteria and viruses

Fig. 3

Temporal distribution of community-acquired pneumonia in patients with respiratory pathogen infections. The area under the curves represents monthly detection rates. The horizontal axis shows the variation in pathogen detection between seasons. The seasons were defined as spring (March to May), summer (June to August), autumn (September to November), and winter (December to February). Data between years (2014–2019) are shown in different colours

Fig. 4

Associations of respiratory pathogens with severe community-acquired pneumonia (CAP). (A) The detection rate of respiratory pathogens and adjusted odds ratios (ORs) in patients with severe CAP and non-severe CAP. ORs adjusted for age (years), sex, season, duration of illness (days), previous antibiotic exposure and underlying diseases. (B) Comparison of the effects of multiple detections and single detection on severe disease

Fig. 5

Cumulative proportion of the ten major pathogens at each sentinel site in community-acquired pneumonia patients. The line chart shows the cumulative positive rates of the ten major site-specific pathogens calculated by taking into account the detection rate and the risk of severe illness according to the site-combined data. The number in the box indicates the ranking of the pathogen detected at that site