title: How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review.
abstract: BACKGROUND
  For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP). A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e. Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected. However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP. We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone.
  
  
  METHODS
  We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP.
  
  
  RESULTS
  Eight relevant studies were selected. In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides. The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens. However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies. As a consequence, the results may have been influenced by confounding by indication. In addition, the outcomes showed several inconsistencies.
  
  
  CONCLUSIONS
  A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies. Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data.
authors.affiliation: Division of Medicine, Department of Acute Medicine and Infectious Diseases, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. j.j.oosterheert@azu.nl
authors.forename: J J
authors.initials: JJ
authors.lastname: Oosterheert
authors.forename: M J M
authors.initials: MJ
authors.lastname: Bonten
authors.forename: E
authors.initials: E
authors.lastname: Hak
authors.forename: M M E
authors.initials: MM
authors.lastname: Schneider
authors.forename: I M
authors.initials: IM
authors.lastname: Hoepelman
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000453:epidemiology; D036262:Empirical Research; D006801:Humans; D018579:Patient Selection; D011014:Pneumonia / Q000188:drug therapy* / Q000453:epidemiology; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents