Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis.

Journal Article (Journal Article;Multicenter Study)

OBJECTIVE: To investigate the efficacy and safety of 4 antipseudomonal treatments in children with cystic fibrosis with recently acquired Pseudomonas aeruginosa infection. DESIGN: Randomized controlled trial. SETTING: Multicenter trial in the United States. PARTICIPANTS: Three hundred four children with cystic fibrosis aged 1 to 12 years within 6 months of P aeruginosa detection. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. TRIAL REGISTRATION: Identifier: NCT00097773.

Full Text

Duke Authors

Cited Authors

  • Treggiari, MM; Retsch-Bogart, G; Mayer-Hamblett, N; Khan, U; Kulich, M; Kronmal, R; Williams, J; Hiatt, P; Gibson, RL; Spencer, T; Orenstein, D; Chatfield, BA; Froh, DK; Burns, JL; Rosenfeld, M; Ramsey, BW; Early Pseudomonas Infection Control (EPIC) Investigators,

Published Date

  • September 2011

Published In

Volume / Issue

  • 165 / 9

Start / End Page

  • 847 - 856

PubMed ID

  • 21893650

Pubmed Central ID

  • PMC3991697

Electronic International Standard Serial Number (EISSN)

  • 1538-3628

Digital Object Identifier (DOI)

  • 10.1001/archpediatrics.2011.136


  • eng

Conference Location

  • United States