title: Azithromycin for prevention of exacerbations of COPD.
abstract: BACKGROUND
  Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.
  
  
  METHODS
  We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.
  
  
  RESULTS
  A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04).
  
  
  CONCLUSIONS
  Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).
authors.affiliation: Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver Health Sciences Center, Denver, CO 80204-4507, USA. ralbert@dhha.org
authors.forename: Richard K
authors.initials: RK
authors.lastname: Albert
authors.forename: John
authors.initials: J
authors.lastname: Connett
authors.forename: William C
authors.initials: WC
authors.lastname: Bailey
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.forename: J Allen D
authors.initials: JA
authors.lastname: Cooper
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.forename: Meilan K
authors.initials: MK
authors.lastname: Han
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Barry
authors.initials: B
authors.lastname: Make
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Marchetti
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Madinger
authors.forename: Charlene
authors.initials: C
authors.lastname: McEvoy
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Niewoehner
authors.forename: Janos
authors.initials: J
authors.lastname: Porsasz
authors.forename: Connie S
authors.initials: CS
authors.lastname: Price
authors.forename: John
authors.initials: J
authors.lastname: Reilly
authors.forename: Paul D
authors.initials: PD
authors.lastname: Scanlon
authors.forename: Frank C
authors.initials: FC
authors.lastname: Sciurba
authors.forename: Steven M
authors.initials: SM
authors.lastname: Scharf
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anthonisen
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000517:prevention & control; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D018942:Macrolides / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000382:microbiology; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017963:Azithromycin