title: Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia.
abstract: BACKGROUND
  The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP.
  
  
  METHODS
  Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns.
  
  
  RESULTS
  Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients.
  
  
  CONCLUSIONS
  Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh.
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Gadsby
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh.|College of Medicine and Veterinary Medicine, University of Edinburgh.
authors.forename: Clark D
authors.initials: CD
authors.lastname: Russell
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh.
authors.forename: Martin P
authors.initials: MP
authors.lastname: McHugh
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mark
authors.affiliation: Department of Anaesthesia, University of Cambridge.
authors.forename: Andrew
authors.initials: A
authors.lastname: Conway Morris
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Laurenson
authors.affiliation: Respiratory Medicine, Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Hill
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Royal Infirmary of Edinburgh.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Templeton
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D058491:Bacterial Load; D017714:Community-Acquired Infections / Q000175:diagnosis / Q000382:microbiology / Q000821:virology; D005260:Female; D006193:Haemophilus influenzae / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000382:microbiology / Q000821:virology; D011024:Pneumonia, Viral / Q000175:diagnosis / Q000382:microbiology / Q000821:virology; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics; D019562:Viral Load
chemical_list: D000900:Anti-Bacterial Agents
keywords: PCR; bacterial load; community-acquired pneumonia; molecular testing; viral