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September 2011

Comparative Efficacy and Safety of 4 Randomized Regimens to Treat Early Pseudomonas aeruginosa Infection in Children With Cystic Fibrosis

Author Affiliations
    † Deceased.

Author Affiliations: Departments of Anesthesiology and Pain Medicine (Dr Treggiari) and Pediatrics (Drs Mayer-Hamblett, Gibson, Burns, Rosenfeld, and Ramsey), Seattle Children's Hospital (Mr Khan and Ms Williams), and Department of Biostatistics, University of Washington (Dr Kronmal), Seattle; Department of Pediatrics, University of North Carolina, Chapel Hill (Dr Retsch-Bogart); Department of Probability and Statistics, Charles University, Prague, Czech Republic (Dr Kulich); Department of Pediatrics, Baylor College of Medicine, Houston, Texas (Dr Hiatt); Department of Pediatrics, Children's Hospital Boston, Boston, Massachusetts (Dr Spencer); Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (Dr Orenstein); Department of Pediatrics, University of Utah, Salt Lake City (Dr Chatfield); and Department of Pediatrics, University of Virginia, Charlottesville (Dr Froh).

Arch Pediatr Adolesc Med. 2011;165(9):847-856. doi:10.1001/archpediatrics.2011.136

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  ClinicalTrials.gov Identifier: NCT00097773.