Advertisement

Impact of antibiotic eradication therapy of Pseudomonas aeruginosa on long term lung function in cystic fibrosis

  • Isabel Gascon Casaredi
    Affiliations
    Division of Respiratory Medicine, Department of Pediatrics, Hospital Sant Joan de Déu de Barcelona, Universidad de Barcelona, Barcelona, Spain

    Division of Respiratory Medicine, Department of Paediatrics, University of Toronto, Toronto, Canada
    Search for articles by this author
  • Michelle Shaw
    Affiliations
    Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada
    Search for articles by this author
  • Valerie Waters
    Affiliations
    Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada

    Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
    Search for articles by this author
  • Ryan Seeto
    Affiliations
    Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada
    Search for articles by this author
  • Ana C. Blanchard
    Affiliations
    Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
    Search for articles by this author
  • Felix Ratjen
    Correspondence
    Corresponding author at: 555 University Avenue, Toronto, Ontario M5G 1X8.
    Affiliations
    Division of Respiratory Medicine, Department of Pediatrics, Hospital Sant Joan de Déu de Barcelona, Universidad de Barcelona, Barcelona, Spain

    Division of Respiratory Medicine, Department of Paediatrics, University of Toronto, Toronto, Canada

    Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada
    Search for articles by this author
Published:August 19, 2022DOI:https://doi.org/10.1016/j.jcf.2022.08.007

      Highlights

      • AET successfully clears Pseudomonas aeruginosa in most individuals.
      • Whether this translate in clinical benefits is less clear.
      • Eradication of Pseudomonas aeruginosa improves lung function trajectories.

      Abstract

      Introduction

      While antibiotic eradication therapy (AET) of early Pseudomonas aeruginosa infection is considered standard of care, its long-term effect on the subsequent course of cystic fibrosis (CF) lung disease remains unclear.

      Methods

      CF patients who were P. aeruginosa-free for at least a year and had a minimum of 10 years of pulmonary function measurements were included. Subjects were categorized as Never if they never had P. aeruginosa isolated from a respiratory tract sample. Subjects changed to the Eradicated group if they had a P. aeruginosa infection, were treated with AET, and subsequently cleared their infection. Subjects changed to the Chronic group if AET did not clear their P. aeruginosa infection. The primary outcome was absolute FEV1 decline over time, with age as the time variable. Mixed-effects linear regression models were used to account for the repeated lung function measurements over time within each patient.

      Results

      205 CF subjects (48% female) were included; the median (IQR) age at first infection was 9.6 (5.6, 14.6) years. The median (IQR) follow-up was 10.2 (5.7, 14.7) years for the Eradicated group, 8.8 (4.5, 14.9) years for the Chronic group and 2.8 (1.0, 5.7) years for the Never group was among those patients that had at least one P. aeruginosa infection over the study period, annual lung function decline of FEV1 was significantly less (-1.11% predicted/year; 95% CI: -1.18, -1.04) in the Eradication group compared to the Chronic group (-1.57%; -1.64, -1.50) (p<0.001).

      Conclusions

      AET against P. aeruginosa improves lung function trajectory in CF patients.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cystic Fibrosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Elborn J.S.
        Cystic fibrosis.
        The Lancet. 2016; 388: 2519-2531
      1. Cystic Fibrosis Foundation. 2018 Patient registry annual data report. Cystic fibrosis foundation patient registry 2018 annual data report. 2018;92.

        • Burgel P.R.
        • Bellis G.
        • Olesen H.V.
        • Viviani L.
        • Zolin A.
        • Blasi F.
        • et al.
        Future trends in cystic fibrosis demography in 34 European countries.
        Eur Respiratory J. 2015; 46: 133-141
        • Bendiak G.
        • Ratjen F.
        CFTR, Mucins, and Mucus in Cystic Fibrosis.
        Semin Respir Crit Care Med. 2009; 30: 587-595
        • Emerson J.
        • Rosenfeld M.
        • McNamara S.
        • Ramsey B.
        • Gibson R.L
        Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis.
        Pediatr Pulmonol. 2002; 34: 91-100
        • Blanchard A.C.
        • Horton E.
        • Stanojevic S.
        • Taylor L.
        • Waters V.
        • Ratjen F
        Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis.
        J Cystic Fibrosis. 2017; 16: 395-400
        • Ratjen F.
        • Moeller A.
        • McKinney M.L.
        • Asherova I.
        • Alon N.
        • Maykut R.
        • et al.
        Eradication of early P. aeruginosa infection in children <7 years of age with cystic fibrosis: the early study.
        J Cystic Fibrosis. 2019; 18: 78-85
        • Ratjen F.
        • Munck A.
        • Kho P.
        • Angyalosi G.
        Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial.
        Thorax. 2010; 65: 286-291
        • Early T.
        Comparative efficacy and safety of 4 randomized regimens to treatearly.
        Arch Pediatric Adol Med. 2011; 165: 847-856
        • Treggiari M.M.
        • Retsch-Bogart G.
        • Mayer-Hamblett N.
        • Khan U.
        • Kulich M.
        • Kronmal R.
        • et al.
        Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis.
        Arch Pediatric Adolescent Med. 2011; 165 (Sep): 847-856
        • Mayer-Hamblett N.
        • Kronmal R.A.
        • Gibson R.L.
        • Rosenfeld M.
        • Retsch-Bogart G.
        • Treggiari M.M.
        • et al.
        Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis.
        Pediatr Pulmonol [Internet]. 2012; 47 (Feb [cited 2022 Jun 6]Available from:): 125-134
        • Nixon G.M.
        • Armstrong D.S.
        • Carzino R.
        • Carlin J.B.
        • Olinsky A.
        • Robertson C.F.
        • et al.
        Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis.
        J Pediatrics. 2001; 138: 699-704
        • Stanojevic S.
        • Davis S.D.
        • Retsch-Bogart G.
        • Webster H.
        • Davis M.
        • Johnson R.C.
        • et al.
        Progression of lung disease in preschool patients with cystic fibrosis.
        Am J Respir Crit Care Med. 2017; 195: 1216-1225
        • Amin R.
        • Lam M.
        • Dupuis A.
        • Ratjen F.
        The effect of early Pseudomonas aeruginosa treatment on lung function in pediatric cystic fibrosis.
        Pediatr Pulmonol. 2011; 46 (Jun): 554-558
        • Santos S.
        • Perrem L.
        • Shaw M.
        • Hewko S.
        • Sanders D.B.
        • Davis S.
        • Stanojevic S.
        • Solomon M.
        • Grasemann H.
        • Sweezey N.
        • Waters V.
        • Ratjen FSantos S.
        • Perrem L.
        • Shaw M.
        • Hewko S.
        • Sanders D.B.
        • Davis S.
        • Stanojevic S.
        • Solomon M.
        • Grasemann H.
        • Sweezey N.
        • Waters V.R.F
        LCI response to acquisition and eradication of Pseudomonas aeruginosa in children with CF.
        Pediatr Pulmonol. 2020; 55 (North American Cystic Fibrosis Conference, October 2020, Phoenix, USA (virtual conference). Pediatr Pulmonol., 48(S36): S471): S38-361
        • Stanojevic S.
        • Waters V.
        • Mathew J.L.
        • Taylor L.
        • Ratjen F
        Effectiveness of inhaled tobramycin in eradicating pseudomonas aeruginosa in children with cystic fibrosis.
        J Cystic Fibrosis. 2014; 13: 172-178
        • Quanjer P.H.
        • Stanojevic S.
        • Cole T.J.
        • Baur X.
        • Hall G.L.
        • Culver B.H.
        • et al.
        Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.
        Eur Respiratory J. 2012; 40: 1324-1343
        • Treggiari M.M.
        • Retsch-Bogart G.
        • Mayer-Hamblett N.
        • Khan U.
        • Kulich M.
        • Kronmal R.
        • et al.
        Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis.
        Arch Pediatr Adolescent Med. 2011; 165 (Sep): 847-856
        • Zemanick E.T.
        • Emerson J.
        • Thompson V.
        • McNamara S.
        • Morgan W.
        • Gibson R.L.
        • et al.
        Clinical outcomes after initial pseudomonas acquisition in cystic fibrosis.
        Pediatr Pulmonol. 2015; 50: 42-48
        • Mayer-Hamblett N.
        • Kloster M.
        • Rosenfeld M.
        • Gibson R.L.
        • Retsch-Bogart G.Z.
        • Emerson J.
        • et al.
        Impact of sustained eradication of new pseudomonas aeruginosa infection on long-term outcomes in cystic fibrosis.
        Clin Infect Dis. 2015; 61: 707-715
        • Frederiksen B.
        • Koch C.
        • Høiby N.
        Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis.
        Pediatr Pulmonol. 1997; 23: 330-335
        • Jackson L.
        • Waters V.
        Factors influencing the acquisition and eradication of early Pseudomonas aeruginosa infection in cystic fibrosis.
        J Cyst Fibros [Internet]. 2021 Jan 1; 20 ([cited 2022 Jun 28]Available from:): 8-16
        • Szczesniak R.D.
        • Li D.
        • Su W.
        • Brokamp C.
        • Pestian J.
        • Seid M.
        • Clancy J.P.
        Phenotypes of rapid cystic fibrosis lung disease progression during adolescence and young adulthood.
        Am J Respir Crit Care Med. 2017 Aug 15; 196: 471-478https://doi.org/10.1164/rccm.201612-2574OC.PMID: 28410569