title: Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes.
abstract: BACKGROUND
  Inhaled antibiotics (ABs) are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF.
  
  
  METHODS
  A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality.
  
  
  RESULTS
  The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3), proportion of adherent patients (>75%-80% of required doses taken) ranged from 86% to 97%; in prospective cohort studies (n=3), adherence rates ranged between 36% and 92%, and in retrospective studies (n=4) it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste), and patient satisfaction.
  
  
  CONCLUSIONS
  The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies) and the lack of a commonly accepted consensus on the definition of adherence in the reviewed articles. Routine adherence monitoring during CF care, discussing the possible reasons of suboptimal adherence with the patient, and changing treatment regimens on the basis of patient burden can individualize CF therapy for patients and may improve the level of adherence.
authors.affiliation: Department of Pediatric Pulmonology, Heim Pál Children's Hospital, Budapest, Hungary; University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary.
authors.forename: Réka
authors.initials: R
authors.lastname: Bodnár
authors.affiliation: University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Mészáros
authors.affiliation: University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary.
authors.forename: Máté
authors.initials: M
authors.lastname: Oláh
authors.affiliation: Syreon Research Institute, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Ágh
keywords: Pseudomonas aeruginosa; adherence; antibiotics; compliance; cystic fibrosis