title: Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis.
abstract: OBJECTIVE
  To investigate the efficacy and safety of 4 antipseudomonal treatments in children with cystic fibrosis with recently acquired Pseudomonas aeruginosa infection.
  
  
  METHODS
  Randomized controlled trial.
  
  
  METHODS
  Multicenter trial in the United States.
  
  
  METHODS
  Three hundred four children with cystic fibrosis aged 1 to 12 years within 6 months of P aeruginosa detection.
  
  
  METHODS
  Participants were randomized to 1 of 4 antibiotic regimens for 18 months (six 12-week quarters) between December 2004 and June 2009. Participants randomized to cycled therapy received tobramycin inhalation solution (300 mg twice a day) for 28 days, with oral ciprofloxacin (15-20 mg/kg twice a day) or oral placebo for 14 days every quarter, while participants randomized to culture-based therapy received the same treatments only during quarters with positive P aeruginosa cultures.
  
  
  METHODS
  The primary end points were time to pulmonary exacerbation requiring intravenous antibiotics and proportion of P aeruginosa -positive cultures.
  
  
  RESULTS
  The intention-to-treat analysis included 304 participants. There was no interaction between treatments. There were no statistically significant differences in exacerbation rates between cycled and culture-based groups (hazard ratio, 0.95; 95% confidence interval [CI], 0.54-1.66) or ciprofloxacin and placebo (hazard ratio, 1.45; 95% CI, 0.82-2.54). The odds ratios of P aeruginosa- positive culture comparing the cycled vs culture-based group were 0.78 (95% CI, 0.49-1.23) and 1.10 (95% CI, 0.71-1.71) comparing ciprofloxacin vs placebo. Adverse events were similar across groups.
  
  
  CONCLUSIONS
  No difference in the rate of exacerbation or prevalence of P aeruginosa positivity was detected between cycled and culture-based therapies. Adding ciprofloxacin produced no benefits.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00097773.
authors: Department of Anesthesiology and Pain Medicine, Seattle Children’s Hospital, WA 98104, USA. treggmm@uw.edu
authors: Miriam M
authors: MM
authors: Treggiari
authors: George
authors: G
authors: Retsch-Bogart
authors: Nicole
authors: N
authors: Mayer-Hamblett
authors: Umer
authors: U
authors: Khan
authors: Michal
authors: M
authors: Kulich
authors: Richard
authors: R
authors: Kronmal
authors: Judy
authors: J
authors: Williams
authors: Peter
authors: P
authors: Hiatt
authors: Ronald L
authors: RL
authors: Gibson
authors: Terry
authors: T
authors: Spencer
authors: David
authors: D
authors: Orenstein
authors: Barbara A
authors: BA
authors: Chatfield
authors: Deborah K
authors: DK
authors: Froh
authors: Jane L
authors: JL
authors: Burns
authors: Margaret
authors: M
authors: Rosenfeld
authors: Bonnie W
authors: BW
authors: Ramsey
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010919:Placebos; D016016:Proportional Hazards Models; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D014031:Tobramycin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010919:Placebos; D002939:Ciprofloxacin; D014031:Tobramycin