TY - JOUR
T1 - Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis
AU - Treggiari, Miriam M.
AU - Retsch-Bogart, George
AU - Mayer-Hamblett, Nicole
AU - Khan, Umer
AU - Kulich, Michal
AU - Kronmal, Richard
AU - Williams, Judy
AU - Hiatt, Peter
AU - Gibson, Ronald L.
AU - Spencer, Terry
AU - Orenstein, David
AU - Chatfield, Barbara A.
AU - Froh, Deborah K.
AU - Burns, Jane L.
AU - Rosenfeld, Margaret
AU - Ramsey, Bonnie W.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
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U2 - 10.1001/archpediatrics.2011.136
DO - 10.1001/archpediatrics.2011.136
M3 - Article
C2 - 21893650
AN - SCOPUS:80052511405
SN - 1072-4710
VL - 165
SP - 847
EP - 856
JO - Archives of Pediatrics and Adolescent Medicine
JF - Archives of Pediatrics and Adolescent Medicine
IS - 9
ER -