title: Clinical cure rates in subjects treated with azithromycin for community-acquired respiratory tract infections caused by azithromycin-susceptible or azithromycin-resistant Streptococcus pneumoniae: analysis of Phase 3 clinical trial data.
abstract: BACKGROUND
  Community-acquired respiratory tract infections (CARTI) are commonly caused by Streptococcus pneumoniae (SPN) and empirically treated with azithromycin. This study assessed clinical cure rates in azithromycin-treated subjects with CARTI caused by azithromycin-susceptible (Azi-S) or azithromycin-resistant (Azi-R) SPN.
  
  
  METHODS
  1127 subjects with CARTI (402 acute otitis media, 309 community-acquired pneumonia, 255 acute bacterial exacerbations of chronic bronchitis and 161 acute bacterial sinusitis) in 13 Phase 3 clinical trials (1993-2007) had a confirmed pathogen, received azithromycin and were assessed for clinical cure/failure. 34.4% of subjects (388/1127) had a positive culture for SPN; 33.4% (376/1127) had Azi-S or Azi-R SPN.
  
  
  RESULTS
  28.9% (112/388) of subjects with SPN had Azi-R SPN: 35.7% (40/112) were low-level Azi-R SPN (LLAR; MIC 2-8 mg/L), while 64.3% (72/112) were high-level Azi-R SPN (HLAR; MIC ≥16 mg/L). Among Azi-S and Azi-R SPN CARTI subjects, clinical cure rates were: 86.2% (324/376) overall; 89.4% (236/264) for subjects with Azi-S SPN; 78.6% (88/112) for subjects with Azi-R SPN (P = 0.003, versus Azi-S); 77.5% (31/40) for subjects with LLAR SPN (P < 0.001); and 79.2% (57/72) for subjects with HLAR SPN (P = 0.122).
  
  
  CONCLUSIONS
  Clinical cure rates in CARTI subjects treated with azithromycin were higher for Azi-S SPN (89.4%) versus Azi-R SPN (78.6%; P = 0.003). However, cure rates were not different for subjects infected with LLAR-SPN versus HLAR-SPN. At the observed prevalence of Azi-R SPN of 28.9%, an additional 3.1 clinical failures would be predicted, as a consequence of azithromycin resistance (LLAR and HLAR), per 100 subjects treated empirically with azithromycin.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Canada ggzhanel@pcs.mb.ca.
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.affiliation: Established Products Clinical Development, Pfizer Inc., New York, NY, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Wolter
authors.affiliation: Medical Affairs, Pfizer Canada Inc., Montreal, Canada.
authors.forename: Cristina
authors.initials: C
authors.lastname: Calciu
authors.affiliation: Specialty Care Business Unit, Pfizer Inc., New York, NY, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hogan
authors.affiliation: Department of Microbiology, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.affiliation: Maisonneuve-Rosemont Hospital, Faculty of Medicine, University of Montreal, Montreal, Canada.
authors.forename: Karl
authors.initials: K
authors.lastname: Weiss
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D017326:Clinical Trials, Phase III as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin
keywords: S. pneumoniae; macrolides; outcome; resistance; susceptibility