title: Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial.
abstract: OBJECTIVE
  In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial.
  
  
  OBJECTIVE
  To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response.
  
  
  METHODS
  Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012.
  
  
  METHODS
  Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission.
  
  
  METHODS
  The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed.
  
  
  RESULTS
  There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34).
  
  
  CONCLUSIONS
  Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00908713.
authors: Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain4Unive.
authors: Antoni
authors: A
authors: Torres
authors: Servei de Pneumologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain6Institut d´Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Oriol
authors: O
authors: Sibila
authors: Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain.
authors: Miquel
authors: M
authors: Ferrer
authors: Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain.
authors: Eva
authors: E
authors: Polverino
authors: Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain7Servicio de Neumologia, Hospital Universitario La Fe, Valencia, Spain.
authors: Rosario
authors: R
authors: Menendez
authors: Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain8Servei de Malalties Infeccioses, Hospital Clinic, Barcelona, Spain.
authors: Josep
authors: J
authors: Mensa
authors: Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain.
authors: Albert
authors: A
authors: Gabarrús
authors: Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain.
authors: Jacobo
authors: J
authors: Sellarés
authors: University of Texas Health Science Center, San Antonio10South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio11VERDICT, San Antonio, Texas.
authors: Marcos I
authors: MI
authors: Restrepo
authors: University of Texas Health Science Center, San Antonio10South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio.
authors: Antonio
authors: A
authors: Anzueto
authors: Winthrop-University Hospital, Mineola, New York.
authors: Michael S
authors: MS
authors: Niederman
authors: Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain.
authors: Carles
authors: C
authors: Agustí
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012131:Respiratory Insufficiency / Q000209:etiology; D012769:Shock / Q000209:etiology; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008775:Methylprednisolone