Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis

Thorax. 2010 Oct;65(10):915-20. doi: 10.1136/thx.2009.126128. Epub 2010 Aug 20.

Abstract

Background: Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF.

Methods: This 3-year triple-blind randomised controlled trial included 65 children with CF without P aeruginosa infection. Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls. The primary outcome was P aeruginosa infection. Secondary outcomes were serum anti-Pseudomonas antibodies, pulmonary function, exacerbations, chest x-ray scores, inflammation parameters, respiratory pathogens and antimicrobial resistance.

Results: There was no difference in acquisition of P aeruginosa infection between the control and treatment groups (annual incidence 14% vs 11%; HR 0.738, 95% CI 0.299 to 1.822). Anti-Pseudomonas antibodies emerged earlier in the control group, but this difference had disappeared after 3 years. Chronic infection was observed in 19% of controls and 12% of treated patients. Decline in pulmonary function and other clinical outcomes did not differ between the two groups. In the treatment group, significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-P aeruginosa non-fermentative Gram-negative bacteria. Conclusions Three-monthly cycled anti-P aeruginosa prophylaxis does not reduce the risk of initial and chronic infection in P aeruginosa-negative children with CF of all ages. Shifts in bacterial colonisation demand caution. Trial Registration Number ISRCTN 11604593.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Antibiotic Prophylaxis / adverse effects
  • Antibiotic Prophylaxis / methods*
  • Antibodies, Bacterial / blood
  • Child
  • Child, Preschool
  • Cystic Fibrosis / complications*
  • Drug Resistance, Bacterial
  • Epidemiologic Methods
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Opportunistic Infections / complications
  • Opportunistic Infections / prevention & control*
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / prevention & control*
  • Pseudomonas aeruginosa* / immunology
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / prevention & control
  • Treatment Outcome

Substances

  • Antibodies, Bacterial

Associated data

  • ISRCTN/ISRCTN11604593