title: Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults.
abstract: BACKGROUND
  Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided to 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense.
  
  
  OBJECTIVE
  To assess the efficacy and need of adding antibiotic coverage for atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to March 2007); and EMBASE (January 1980 to January 2007).
  
  
  METHODS
  Randomized trials of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a regimen without atypical antibiotic coverage.
  
  
  METHODS
  Two review authors independently appraised the quality of each trial and extracted the data from included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated, assuming an intention-to-treat (ITT) basis for the outcome measures.
  
  
  RESULTS
  Twenty five trials were included, encompassing 5244 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.15; 95% CI 0.85 to 1.56). The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high-quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). All but two included trials compared a single atypical antibiotic to a beta-lactam, while no trials assessing the addition of an atypical antibiotic to a beta-lactam were identified.
  
  
  CONCLUSIONS
  No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams (BL) or cephalosporins. Further trials, comparing BL or cephalosporins therapy to BL or cephalosporins combined with a macrolide in this population, using mortality as its primary outcome, should be performed.
authors.affiliation: Campus Beilinson, Dept of Medicine E, Rabin Medical Center, Petah-Tikva, Israel, 49100. robensht@netvision.net.il
authors.forename: E
authors.initials: E
authors.lastname: Robenshtok
authors.forename: D
authors.initials: D
authors.lastname: Shefet
authors.forename: A
authors.initials: A
authors.lastname: Gafter-Gvili
authors.forename: M
authors.initials: M
authors.lastname: Paul
authors.forename: L
authors.initials: L
authors.lastname: Vidal
authors.forename: L
authors.initials: L
authors.lastname: Leibovici
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D016032:Randomized Controlled Trials as Topic
chemical_list: D000900:Anti-Bacterial Agents