title: Guidelines-concordant empiric antimicrobial therapy and mortality in patients with severe community-acquired pneumonia requiring mechanical ventilation.
abstract: BACKGROUND
  Community-acquired pneumonia (CAP) has high morbidity and mortality among adults. Several clinical guidelines recommend prompt administration of combined antimicrobial therapy. However, the association between guidelines concordance and mortality in patients with severe pneumonia remains unclear. The present study aimed to examine the impact of guidelines-concordant empiric antimicrobial therapy on 7-day mortality in patients with extremely severe pneumonia who required mechanical ventilation at admission, using a nationwide inpatient database in Japan.
  
  
  METHODS
  Data of CAP patients aged over 20 years who required mechanical ventilation at admission between April 2012 and March 2014 were retrospectively analyzed. Multivariable logistic regression analysis was performed to examine the association between guidelines-concordant empiric antimicrobial therapy and all-cause 7-day mortality, with adjustment for patient backgrounds and pneumonia severity.
  
  
  RESULTS
  There were a total of 3719 eligible patients, 836 (22.5%) of whom received guidelines-concordant combination therapy. Overall, 7-day mortality was 29.5%. Higher 7-day mortality was associated with advanced age, confusion, lower systolic blood pressure, malignant tumor or immunocompromised state, and C-reactive protein ≥20mg/dl or infiltration occupying two-thirds of one lung on chest radiography. After adjustment for these variables, guidelines-concordant combined antimicrobial therapy was associated with significantly lower 7-day mortality (odds ratio: 0.78; 95% confidence interval: 0.65-0.95; P=0.013).
  
  
  CONCLUSIONS
  Adherence to initial empiric treatment as recommended by the guidelines was associated with better short-term prognosis in patients with extremely severe pneumonia who required mechanical ventilation on hospital admission.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: ysakamoto-tmd@umin.org.
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: YAMAUCHIY-INT@h.u-tokyo.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.affiliation: Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: yasunagah-tky@umin.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasunaga
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: Htakeshima-tky@umin.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeshima
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: w-hasegawa@umin.ac.jp.
authors.forename: Wakae
authors.initials: W
authors.lastname: Hasegawa
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: jo-taisuke@umin.ac.jp.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Jo
authors.affiliation: Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: ptmatsui-tky@umin.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: kfushimi.hci@tmd.ac.jp.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fushimi
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: takahide-tky@umin.ac.jp.
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000401:mortality*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000401:mortality*; D017410:Practice Guidelines as Topic; D012121:Respiration, Artificial / Q000401:mortality*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000493:Allopurinol
keywords: 7-day mortality; Combined antimicrobial therapy; Community-acquired pneumonia; Extremely severe pneumonia; Guidelines