title: Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response.
abstract: OBJECTIVE
  Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP.
  
  
  METHODS
  This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups.
  
  
  RESULTS
  From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients.
  
  
  CONCLUSIONS
  Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.
authors.affiliation: Section of Infectious Diseases, Providence Hospital, Washington, DC, 20017, USA. jbordon@provhosp.org.
authors.forename: J M
authors.initials: JM
authors.lastname: Bordon
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fernandez-Botran
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Wiemken
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Peyrani
authors.affiliation: Division of Nephrology, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Uriarte
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Arnold
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rodriquez-Hernandez
authors.affiliation: Division of Nephrology, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Rane
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Kelley
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Binford
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Uppatla
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Cavallazzi
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Ca` Granda Ospedale Maggiore, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Blasi
authors.affiliation: Respiratory Unit, Department of Health Science, University of Milan Bicocca, AO San Gerardo, Monza, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aliberti
authors.affiliation: Department of Pulmonary Diseases, South Texas Veterans Health Care System and University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Restrepo
authors.affiliation: Section of Infectious Diseases, Providence Hospital, Washington, DC, 20017, USA.
authors.forename: S
authors.initials: S
authors.lastname: Fazeli
authors.affiliation: Section of Infectious Diseases, Providence Hospital, Washington, DC, 20017, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mathur
authors.affiliation: Section of Infectious Diseases, Providence Hospital, Washington, DC, 20017, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rahmani
authors.affiliation: Department of Internal Medicine, Orlando Health, Florida, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ayesu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.|Veterans Administration Medical Center, Louisville, KY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ramirez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D017714:Community-Acquired Infections / Q000382:microbiology / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010949:Plasma / Q000737:chemistry; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000473:pathology*; D011446:Prospective Studies; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016207:Cytokines; D020097:Natriuretic Peptide, Brain; D002116:Calcitonin; D002097:C-Reactive Protein
keywords: Biomarkers; Chemokines; Community-acquired pneumonia; Cytokines; Inflammatory response; Mortality; Neutrophil functional responses; Outcome; Pneumococcal bacteremia; Pneumonia severity; Streptococcus pneumoniae