title: Maintenance azithromycin treatment in pediatric patients with cystic fibrosis: long-term outcomes related to macrolide resistance and pulmonary function.
abstract: BACKGROUND
  Maintenance azithromycin therapy may improve pulmonary function in patients with cystic fibrosis (CF) with Pseudomonas aeruginosa infection because of its antiinflammatory properties. However, azithromycin therapy might increase macrolide resistance in Staphylococcus aureus cultured from respiratory secretions. We studied the emergence of macrolide resistance in S. aureus and correlated this to pulmonary function decline in pediatric patients with CF on daily azithromycin therapy.
  
  
  METHODS
  Respiratory cultures of 100 patients with CF were analyzed for S. aureus colonization and its resistance pattern before and during 3 years after initiation of azithromycin maintenance therapy. Mean annual change in forced expiratory volume as percent of predicted (FEV1 %) was calculated to compare pulmonary function before and after azithromycin therapy.
  
  
  RESULTS
  Staphylococcal colonization did not significantly decrease after initiation of azithromycin (50% versus 48%). Before start of therapy, 10% of patients with staphylococcal colonization had macrolide-resistant strains. Staphylococcal resistance increased to 83% in the first year; 97% in the second and 100% in the third year after initiation of azithromycin therapy (P < 0.001). Half of macrolide-resistant S. aureus comprised the macrolide-lincosamide-streptogramin phenotype. Percent forced expiratory volume in 1 second improved in the first year after initiation of azithromycin (mean annual change: -4.75% before versus +3.09% after initiation; P < 0.01) but decreased during the second and third years after initiation (-5.15% and -3.65%, respectively). Emergence of macrolide-resistant S. aureus was not related to pulmonary function decline.
  
  
  CONCLUSIONS
  Maintenance azithromycin therapy in patients with CF leads to macrolide resistance in nearly all S. aureus carriers. Pulmonary function improvement after initiation of azithromycin therapy seems to be temporary and appears not to be related to macrolide resistance of S. aureus.
authors.affiliation: Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gerdien A
authors.initials: GA
authors.lastname: Tramper-Stranders
authors.forename: Tom F W
authors.initials: TF
authors.lastname: Wolfs
authors.forename: André
authors.initials: A
authors.lastname: Fleer
authors.forename: Jan L L
authors.initials: JL
authors.lastname: Kimpen
authors.forename: Cornelis K
authors.initials: CK
authors.lastname: van der Ent
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000503:physiopathology; D004351:Drug Resistance; D004352:Drug Resistance, Microbial; D006801:Humans; D007223:Infant; D008168:Lung / Q000382:microbiology / Q000503:physiopathology; D018942:Macrolides / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017963:Azithromycin