title: Increase in fitness of Streptococcus pneumoniae is associated with the severity of necrotizing pneumonia.
abstract: BACKGROUND
  The incidence of necrotizing pneumococcal pneumonia has increased during the past 2 decades. We hypothesized that increased pneumococcal load or augmented inflammatory cytokine production might lead to destructive pneumococcal lung disease.
  
  
  METHODS
  This study enrolled prospectively 0- to 18-year-old children with a diagnosis of community-acquired pneumonia with pleural effusion admitted to 6 medical centers from March 2010 to April 2012. Children were diagnosed with pneumococcal empyema if the pleural fluid tested positive for quantitative pneumococcal (lytA) detection by real-time polymerase chain reaction. Pneumococcal empyema cases were further divided into 4 groups according to necrosis severity: (0) nonnecrosis, (1) mild necrosis, (2) cavitation and (3) bronchopleural fistula. Nasopharyngeal and pleural pneumococcal load, as well as levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8), Th1-(IL-2, IFN-γ), Th2-(IL-4, IL-10) and Th17-cytokines (IL-17), in the pleural fluid was measured.
  
  
  RESULTS
  Serotypes 19A and 3 accounted for 69.4% and 12.5%, respectively, of 72 cases of pneumococcal empyema. Pleural pneumococcal load was significantly higher in serotypes 19A and 3 infection than in the other strains causing infection (P = 0.006). There was a correlation between nasopharyngeal and pleural pneumococcal load (ρ = 0.35; P = 0.05). In multivariate ordinal logistic regression analysis, pleural pneumococcal load (adjusted odds ratio: 1.79; 95% confidence interval: 1.03-3.06) and IL-8 (adjusted odds ratio: 2.64; 95% confidence interval: 1.21-5.75) were independent factors associated with the severity of lung necrosis.
  
  
  CONCLUSIONS
  Evolution of Streptococcus pneumoniae toward increased fitness in their interaction with host and exaggerated IL-8 expression may be responsible for the increase of necrotizing pneumococcal pneumonia.
authors.affiliation: From the *Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan; †Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; ‡Division of Biostatistics, Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; §Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan; ¶Bacterial Enteric and Emerging Diseases Laboratory, Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan; ‖Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; **Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; ††Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan; and ‡‡Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Hsin
authors.initials: H
authors.lastname: Chi
authors.forename: Kuang-Yi
authors.initials: KY
authors.lastname: Chang
authors.forename: Shen-Hao
authors.initials: SH
authors.lastname: Lai
authors.forename: Jung-Jung
authors.initials: JJ
authors.lastname: Mu
authors.forename: Kin-Sun
authors.initials: KS
authors.lastname: Wong
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Huang
authors.forename: Hsiao-Chuan
authors.initials: HC
authors.lastname: Lin
authors.forename: Luan-Yin
authors.initials: LY
authors.lastname: Chang
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
mesh_terms: D000704:Analysis of Variance; D058491:Bacterial Load; D016207:Cytokines / Q000097:blood; D004653:Empyema; D006801:Humans; D015994:Incidence; D008168:Lung / Q000000981:diagnostic imaging / Q000382:microbiology / Q000473:pathology; D009305:Nasopharynx / Q000382:microbiology; D009336:Necrosis / Q000453:epidemiology* / Q000382:microbiology* / Q000503:physiopathology; D011018:Pneumonia, Pneumococcal / Q000453:epidemiology* / Q000382:microbiology* / Q000503:physiopathology; D011446:Prospective Studies; D011859:Radiography; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*
chemical_list: D016207:Cytokines