title: Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis.
abstract: BACKGROUND
  Antibiotic eradication therapy (AET) for initial Pseudomonas aeruginosa (Pa) infection is standard of care in children with cystic fibrosis (CF), but information is limited on treatment for patients who fail initial AET. The aim of this study was to evaluate the effectiveness of a multi-step protocol for AET for new-onset Pa infections in children with CF.
  
  
  METHODS
  A three-step AET protocol which includes: (step 1) 28days of tobramycin inhalation solution (TIS) for new-onset Pa infection; (step 2) a second course of TIS for patients with positive respiratory tract culture after step 1; (step 3) 14days of intravenous antibiotics followed by 28days of TIS for patients with a subsequent positive culture. We conducted a retrospective review of all pediatric CF patients who underwent the eradication protocol between January 2010 and December 2015. The success rate of each step and of the overall protocol was recorded.
  
  
  RESULTS
  During the study period, 128 patients had a total of 213 new-onset Pa infections. Of 195 asymptomatic episodes, 150 (76.9%, 95% CI 70.4; 82.6) cleared after step 1 and 12 cleared after step 2 (33.3% (95% CI 18.6; 50.9) stepwise success rate and 87.1% (95% CI 77.1; 88.1) cumulative success rate). Intravenous antibiotics followed by 28days of TIS were administered in 24 episodes; this was successful in 10 episodes (41.7%; 95% CI 22.1; 63.4). The regimen in asymptomatic patients failed in fourteen episodes (7.5%; 95% CI 4.2; 12.3) then considered chronically infected with Pa. Overall, the cumulative success rate of the asymptomatic arm was 88.2% (95% CI 82.8; 92.4).
  
  
  CONCLUSIONS
  The first step of the AET protocol led to the greatest eradication success. Subsequent eradication attempts have a success rate below 50%. Prospective studies of eradication protocols for this population are needed to determine the most effective treatment strategy.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: ana.blanchard@sickkids.ca.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Blanchard
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Eric.horton@sickkids.ca.
authors.forename: Eric
authors.initials: E
authors.lastname: Horton
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: sanja.stanojevic@sickkids.ca.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stanojevic
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: louise.taylor@sickkids.ca.
authors.forename: Louise
authors.initials: L
authors.lastname: Taylor
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: valerie.waters@sickkids.ca.
authors.forename: Valerie
authors.initials: V
authors.lastname: Waters
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: felix.ratjen@sickkids.ca.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000145:classification; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054539:Medication Therapy Management / Q000706:statistics & numerical data*; D015397:Program Evaluation; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antibiotic eradication therapy; Cystic fibrosis; Eradication failure; Pseudomonas aeruginosa infection