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Prevalence, trends and outcomes of long-term inhaled antibiotic treatment in people with cystic fibrosis without chronic Pseudomonas aeruginosa infection – A European cystic fibrosis patient registry data analysis

Published:August 28, 2022DOI:https://doi.org/10.1016/j.jcf.2022.08.010

      Highlights

      • We searched the ECFS-PR for inhaled antibiotic use in pwCF without PA infection.
      • 30% of pwCF not chronically PA infected were treated with inhaled antibiotics.
      • The major determinant of inhaled antibiotic use is past chronic infection with PA.
      • Over follow up, no benefit has been seen for treatment with inhaled antibiotics.
      • Randomized trials of inhaled antibiotics in pwCF without PA infection are needed.

      Abstract

      Background

      Long-term treatment with inhaled antibiotics is recommended for people with cystic fibrosis (pwCF) chronically infected with Pseudomonas aeruginosa (PA). However, pwCF without chronic PA infection are also commonly treated with inhaled antibiotics. Using data from the European Cystic Fibrosis Patient Registry (ECFSPR) we aimed to determine the prevalence and factors associated with inhaled antibiotic treatment in pwCF without chronic PA infection, and long-term outcomes with inhaled antibiotics use.

      Methods

      The ECFSPR was searched for pwCF 6 years of age and older who were not chronically infected with PA at baseline. Factors associated with inhaled antibiotic use were first assessed through a logistic regression. From this model a propensity score was computed for each individual, providing the likelihood of being treated with inhaled antibiotics. Long-term outcomes with and without inhaled antibiotics were assessed separately for propensity scores tertiles.

      Results

      7210 pwCF without chronic PA infection at baseline were included, with 2722 (37.75%) receiving long-term treatment with inhaled antibiotics. Treatment with inhaled antibiotics was more prevalent with severe genotype, diabetes, pancreatic insufficiency, and past infection with chronic PA (OR 3.8, 95% CI, 2.88–5.04). Treatment with inhaled antibiotics was not associated with a reduced risk for acquisition of PA or other resistant pathogens, or with improved lung function decline, mortality, or transplantation.

      Conclusions

      Many pwCF without chronic PA infection are receiving long-term treatment with inhaled antibiotics despite lack of support from clinical trials or practice guidelines. We did not observe improve outcomes with inhaled antibiotics. Our findings suggest controlled studies evaluating specific inhaled antibiotic regimens targeting specific pathogens or indications be performed to determine their effect.

      Graphical abstract

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      References

        • Ramsey B.W.
        • Pepe M.S.
        • Quan J.M.
        • Otto K.L.
        • Montgomery A.B.
        • Williams-Warren J.
        • et al.
        Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic fibrosis inhaled tobramycin study group.
        N Engl J Med. 1999; 340 (Jan 7): 23-30
        • Hodson M.E.
        • Gallagher C.G.
        • Govan J.R.W.
        A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis.
        Eur Respir J. 2002; 20 (Sep): 658-664
        • Elborn J.S.
        • Flume P.A.
        • Cohen F.
        • Loutit J.
        • Van Devanter D.R.
        Safety and efficacy of prolonged levofloxacin inhalation solution (APT-1026) treatment for cystic fibrosis and chronic Pseudomonas aeruginosa airway infection.
        J Cyst Fibros. 2016; 15 (Sep): 634-640
        • Ryan G.
        • Singh M.
        • Dwan K.
        Inhaled antibiotics for long-term therapy in cystic fibrosis.
        Cochrane Database Syst Rev. 2011; (Mar 16)CD001021
        • Smith S.
        • Rowbotham N.J.
        • Regan K.H.
        Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.
        Cochrane Database Syst Rev. 2018; 3 (Mar 30)CD001021
        • Konstan M.W.
        • Geller D.E.
        • Minić P.
        • Brockhaus F.
        • Zhang J.
        • Angyalosi G.
        Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: the EVOLVE trial.
        Pediatr Pulmonol. 2011; 46 (Mar): 230-238
        • Jensen T.
        • Pedersen S.S.
        • Garne S.
        • Heilmann C.
        • Høiby N.
        • Koch C.
        Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.
        J Antimicrob Chemother. 1987; 19 (Jun): 831-838
        • McCoy K.S.
        • Quittner A.L.
        • Oermann C.M.
        • Gibson R.L.
        • Retsch-Bogart G.Z.
        • Montgomery A.B.
        Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis.
        Am J Respir Crit Care Med. 2008; 178 (Nov 1): 921-928
        • Castellani C.
        • Duff A.J.A.
        • Bell S.C.
        • Heijerman H.G.M.
        • Munck A.
        • Ratjen F.
        • et al.
        ECFS best practice guidelines: the 2018 revision.
        J Cyst Fibros. 2018; 17 (Mar 3): 153-178
        • Mogayzel P.J.
        • Naureckas E.T.
        • Robinson K.A.
        • Mueller G.
        • Hadjiliadis D.
        • Hoag J.B.
        • et al.
        Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health.
        Am J Respir Crit Care Med. 2013; 187 (Apr 1): 680-689
      1. Zolin A., Orenti A., Naerlich L., Jung A., van Rens J. ECFSPR annual report 2018. European cystic fibrosis, … [Internet]. 2020 [cited 2021 Nov 26]; Available from: https://www.ecfs.eu/projects/ecfs-patient-registry/annual-reports

        • Keating C.L.
        • Zuckerman J.B.
        • Singh P.K.
        • McKevitt M.
        • Gurtovaya O.
        • Bresnik M.
        • et al.
        Pseudomonas aeruginosa susceptibility patterns and associated clinical outcomes in people with cystic fibrosis following approval of aztreonam lysine for inhalation.
        Antimicrob Agents Chemother. 2021; 65 (Feb 17)
        • Xu M.J.
        • Dai B.
        Inhaled antibiotics therapy for stable non-cystic fibrosis bronchiectasis: a meta-analysis.
        Ther Adv Respir Dis. 2020; 14 (Dec1753466620936866)
        • Saad A.
        • Young M.R.
        • Studtmann A.E.
        • Autry E.B.
        • Schadler A.
        • Beckman E.J.
        • et al.
        Incidence of nephrotoxicity with prolonged aminoglycoside exposure in patients with cystic fibrosis.
        Pediatr Pulmonol. 2020; 55 (Dec): 3384-3390
        • Elson E.C.
        • Meier E.
        • Oermann C.M.
        The implementation of an aminoglycoside induced ototoxicity algorithm for people with cystic fibrosis.
        J Cyst Fibros. 2021; 20 (Mar): 284-287
        • Rowbotham N.J.
        • Smith S.
        • Leighton P.A.
        • Rayner O.C.
        • Gathercole K.
        • Elliott Z.C.
        • et al.
        The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers.
        Thorax. 2018; 73: 388-390
      2. Diagnosis E. Variables, inclusion criteria and definitions used by the ECFSPR (from follow-up year 2021) [Internet]. cited 2021 Nov 27. Available from: https://www.ecfs.eu/projects/ecfs-patient-registry/Variables-Definitions

        • Lee T.W.R.
        • Brownlee K.G.
        • Conway S.P.
        • Denton M.
        • Littlewood J.M.
        Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.
        J Cyst Fibros. 2003; 2 (Mar): 29-34
        • Zielenski J.
        • Tsui L.C.
        Cystic fibrosis: genotypic and phenotypic variations.
        Annu Rev Genet. 1995; 29: 777-807
      3. World development indicators | DataBank [Internet]. [cited 2021 Nov 23]. Available from: https://databank.worldbank.org/reports.aspx?source=2&series=NY.GNP.PCAP.CD&country=#advancedDownloadOptions

      4. Guo S., Fraser M.W. Propensity score analysis: statistical methods and applications. books.google.com; 2014.

        • Loebinger M.R.
        • Polverino E.
        • Chalmers J.D.
        • Tiddens H.A.W.M.
        • Goossens H.
        • Tunney M.
        • et al.
        Efficacy and safety of TOBI podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study.
        Eur Respir J. 2021; 57 (Jan 5)
        • 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 Adolesc Med. 2011; 165 (Sep): 847-856
        • Mayer-Hamblett N.
        • Rosenfeld M.
        • Treggiari M.M.
        • Konstan M.W.
        • Retsch-Bogart G.
        • Morgan W.
        • et al.
        Standard care versus protocol based therapy for new onset Pseudomonas aeruginosa in cystic fibrosis.
        Pediatr Pulmonol. 2013; 48 (Oct): 943-953
        • Floto R.A.
        • Olivier K.N.
        • Saiman L.
        • Daley C.L.
        • Herrmann J.L.
        • Nick J.A.
        • et al.
        US cystic fibrosis foundation and European cystic fibrosis society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis.
        Thorax. 2016; 71 (JanSuppl 1): i1-22
        • Kennedy S.
        • Beaudoin T.
        • Yau Y.C.W.
        • Caraher E.
        • Zlosnik J.E.A.
        • Speert D.P.
        • et al.
        Activity of tobramycin against cystic fibrosis isolates of Burkholderia cepacia Complex Grown as Biofilms.
        Antimicrob Agents Chemother. 2016; 60: 348-355
        • Abbott I.J.
        • Peleg A.Y
        Stenotrophomonas, Achromobacter, and nonmelioid Burkholderia species: antimicrobial resistance and therapeutic strategies.
        Semin Respir Crit Care Med. 2015; 36 (Feb 2): 99-110
        • Wang M.
        • Ridderberg W.
        • Hansen C.R.
        • Høiby N.
        • Jensen-Fangel S.
        • Olesen H.V.
        • et al.
        Early treatment with inhaled antibiotics postpones next occurrence of achromobacter in cystic fibrosis.
        J Cyst Fibros. 2013; 12 (Dec): 638-643
        • Çelik D.D.
        • Nørskov-Lauritsen N.
        • Çelik B.Ö.
        Comparative in vitro activities of meropenem in combination with colistin, levofloxacin, or chloramphenicol against achromobacter xylosoxidans strains isolated from patients with cystic fibrosis.
        J Glob Antimicrob Resist. 2020; (Jun 10)
        • Tullis D.E.
        • Burns J.L.
        • Retsch-Bogart G.Z.
        • Bresnik M.
        • Henig N.R.
        • Lewis S.A.
        • et al.
        Inhaled aztreonam for chronic Burkholderia infection in cystic fibrosis: a placebo-controlled trial.
        J Cyst Fibros. 2014; 13 (May 1): 296-305
        • Frost F.
        • Shaw M.
        • Nazareth D.
        Antibiotic therapy for chronic infection with Burkholderia cepacia complex in people with cystic fibrosis.
        Cochrane Database Syst Rev. 2021; 12 (Dec 10)CD013079
        • Mooney L.
        • Kerr K.G.
        • Denton M.
        Survival of Stenotrophomonas maltophilia following exposure to concentrations of tobramycin used in aerosolized therapy for cystic fibrosis patients.
        Int J Antimicrob Agents. 2001; 17 (Jan): 63-66
        • Talmaciu I.
        • Varlotta L.
        • Mortensen J.
        • Schidlow D.V.
        Risk factors for emergence of Stenotrophomonas maltophilia in cystic fibrosis.
        Pediatr Pulmonol. 2000; 30 (Jul 1): 10-15