Article

Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis

Department of Pediatrics, University of Washington/Children's Hospital & Regional Medical Center, Seattle, WA 98105-0371, USA.
Pediatric Pulmonology (Impact Factor: 2.3). 07/2007; 42(7):610-23. DOI: 10.1002/ppul.20625
Source: PubMed

ABSTRACT Among young children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) airway infection is associated with increased morbidity and mortality. Early intervention strategies include tobramycin solution for inhalation (TSI), which can eradicate lower airway Pa from cultures obtained at the end of 28 days of treatment in young children.
We conducted an open label, sequential cohort study of TSI in young children with CF to investigate duration of antimicrobial treatment effect. The primary outcome was lower airway Pa eradication per bronchoalveolar lavage (BAL) fluid culture. Sequential treatment cohorts varied by duration of treatment (28 or 56 days) and timing of follow-up BAL (at Days 56, 84, or 112). Subjects (N = 36) were treated with TSI, 300 mg twice daily, for 28 days or 56 days per cohort assignment.
Among 31 evaluable subjects, culture based, lower airway Pa eradication was observed in the majority of subjects for up to 1-3 months following TSI treatment: 75% in Cohort 28/56 (days of treatment/day of follow-up BAL), 63% in Cohort 28/84, 82% in Cohort 56/112, and 75% in Cohort 28/112. Non-mucoid Pa at baseline and/or exotoxin A seronegativity were associated with higher rates of eradication. There was a less pronounced effect of TSI treatment on Pa eradication from oropharyngeal cultures in all cohorts. TSI treatment was associated with reduced neutrophilic airway inflammation and was not related to any serious adverse events.
TSI monotherapy is safe and can eradicate lower airway Pa for up to 3 months after treatment in young children with CF.

Full-text

Available from: Richard B Moss, Jun 11, 2015
0 Followers
 · 
212 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pseudomonas aeruginosa is the main pathogen in bronchopulmonary infections in cystic fibrosis (CF) patients. It can only be eradicated at early infection stages while reduction of its bacterial load is the therapeutic goal during chronic infection or exacerbations. Neonatal screening and pharmacokinetic/pharmacodynamic knowledge has modified the management of CF-patients. A culture based microbiological follow-up should be performed in patients with no infection with P.aeruginosa. At initial infection, inhaled colistin (0,5-2MU/tid), tobramycin (300mg/bid) or aztreonam (75mg/tid) with or without oral ciprofloxacin (15-20mg/kg/bid, 2-3weeks) are recommended. In chronic infections, treatment is based on continuous administration of colistin or with a 28-day on-off regimen with tobramycin or aztreonam. During mild-moderate exacerbations oral ciprofloxacin (2-3weeks) can be administered while serious exacerbations must be treated with intravenous combination therapy (beta-lactam with an aminoglycoside or a fluoroquinolone). Future studies will support antibiotic rotation and/or new combination therapies. Epidemiological measures are also recommended to avoid new P.aeruginosa infections and "patient-to-patient transmission" of this pathogen. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.
    Archivos de Bronconeumología 01/2015; 51(3). DOI:10.1016/j.arbres.2014.09.021 · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cystic fibrosis (CF) is the most common life-shortening genetic disorder in Caucasians. With improved diagnosis and treatment, survival has steadily increased. Unfortunately, the overwhelming majority of patients still die from respiratory failure caused by structural damage resulting from airway obstruction, recurrent infection, and inflammation. Here, we discuss the role of inflammation and the development of anti-inflammatory therapies to treat CF lung disease. The inflammatory host response is the least addressed component of CF airway disease at this time. Current challenges in both preclinical and clinical investigation make the identification of suitable anti-inflammatory drugs more difficult. Despite this, many researchers are making significant progress toward this goal and the CF research community has reason to believe that new therapies will emerge from these efforts.
    Journal of Inflammation Research 08/2010; 3:61-74.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic infection with Burkholderia cepacia complex species remains a significant problem for clinicians treating people with cystic fibrosis. Colonisation with Burkholderia cepacia complex species is linked to a more rapid decline in lung function and increases morbidity and mortality. There remain no objective guidelines for strategies to eradicate Burkholderia cepacia complex in cystic fibrosis lung disease, as these are inherently resistant to the majority of antibiotics and there has been very little research in this area. This review aims to examine the current treatment options for people with cystic fibrosis with acute of Burkholderia cepacia complex and to identify an evidence-based strategy that is both safe and effective.
    Cochrane database of systematic reviews (Online) 01/2014; 10(10):CD009876. DOI:10.1002/14651858.CD009876.pub2 · 5.70 Impact Factor