title: Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis.
abstract: BACKGROUND
  Macrolides are used to treat pneumonia despite increasing antimicrobial resistance. However, the immunomodulatory properties of macrolides may have a favorable effect on pneumonia outcomes. Therefore, we systematically reviewed all studies of macrolide use and mortality among patients hospitalized with community-acquired pneumonia (CAP).
  
  
  METHODS
  All randomized control trials (RCTs) and observational studies comparing macrolides to other treatment regimens in adults hospitalized with CAP were identified through electronic databases and gray literature searches. Primary analysis examined any macrolide use and mortality; secondary analysis compared Infectious Diseases Society of America/American Thoracic Society guideline-concordant macrolide/beta-lactam combinations vs respiratory fluoroquinolones. Random effects models were used to generate pooled risk ratios (RRs) and evaluate heterogeneity (I(2)).
  
  
  RESULTS
  We included 23 studies and 137,574 patients. Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (3.7% [1738 of 47,071] vs 6.5% [5861 of 90,503]; RR, 0.78; 95% confidence interval [CI], .64-.95; P = .01; I(2)= 85%). There was no survival advantage and heterogeneity was reduced when analyses were restricted to RCTs (4.6% [22 of 479] vs 4.1% [25 of 613]; RR, 1.13; 95% CI, .65-1.98; P = .66; I(2)= 0%) or to patients treated with guideline-concordant antibiotics (macrolide/beta-lactam, 5.3% [297 of 5574] vs respiratory fluoroquinolones, 5.8% [408 of 7050]; RR, 1.17; 95% CI, .91-1.50; P = .22; I(2)= 43%).
  
  
  CONCLUSIONS
  In hospitalized patients with CAP, macrolide-based regimens were associated with a significant 22% reduction in mortality compared with nonmacrolides; however, this benefit did not extend to patients studied in RCTs or patients that received guideline-concordant antibiotics. Our findings suggest guideline concordance is more important than choice of antibiotic when treating CAP.
authors.affiliation: Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Leyla
authors.initials: L
authors.lastname: Asadi
authors.forename: Wendy I
authors.initials: WI
authors.lastname: Sligl
authors.forename: Dean T
authors.initials: DT
authors.lastname: Eurich
authors.forename: Isabelle N
authors.initials: IN
authors.lastname: Colmers
authors.forename: Lisa
authors.initials: L
authors.lastname: Tjosvold
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Marrie
authors.forename: Sumit R
authors.initials: SR
authors.lastname: Majumdar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D006801:Humans; D018942:Macrolides / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides