Original Article|Articles in Press

Antibiotics and outcomes of CF pulmonary exacerbations in children infected with MRSA and Pseudomonas aeruginosa

Published:August 07, 2022DOI:


      • Polymicrobial infections in people with cystic fibrosis are common.
      • Optimal treatment strategies for polymicrobial infections are not known.
      • Antibiotic treatment for all known endobronchial infections may not be needed.


      Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone.


      Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting.


      943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics.


      Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.


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        • Ferkol T
        • Rosenfeld M
        • Milla CE.
        Cystic fibrosis pulmonary exacerbations.
        J Pediatr. 2006; 148: 259-264
        • Goss CH
        • Burns JL.
        Exacerbations in cystic fibrosis. 1: epidemiology and pathogenesis.
        Thorax. 2007; 62: 360-367
        • Waters V
        • Stanojevic S
        • Atenafu EG
        • et al.
        Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis.
        Eur Respir J. 2012; 40: 61-66
        • Britto MT
        • Kotagal UR
        • Hornung RW
        • Atherton HD
        • Tsevat J
        • Wilmott RW.
        Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis.
        Chest. 2002; 121: 64-72
        • Cogen JD
        • Oron AP
        • Gibson RL
        • et al.
        Characterization of inpatient cystic fibrosis pulmonary exacerbations.
        Pediatrics. 2017; 139e20162642
        • Flume PA
        • Mogayzel PJ
        • Robinson KA
        • et al.
        Cystic fibrosis pulmonary guidelines. Treatment of pulmonary exacerbations.
        Am J Respir Crit Care Med. 2009; 180: 802-808
      1. Cystic Fibrosis Foundation. Cystic fibrosis foundation patient registry 2020 annual data report. Bethesda, MD: cystic fibrosis foundation. 2010. Available at:

      2. Ahern S, Salimi F, Caruso M, et al. The Australian Cystic Fibrosis Data Registry Annual Report 2020. Available at:

        • Hatziagorou E
        • Orenti A
        • Drevinek P
        • et al.
        Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis-data from the European cystic fibrosis society patient registry.
        J Cyst Fibros. 2020; 19: 376-383
        • Sawicki GS
        • Rasouliyan L
        • Pasta DJ
        • et al.
        The impact of incident methicillin resistant staphylococcus aureus detection on pulmonary function in cystic fibrosis.
        Pediatr Pulmonol. 2008; 43: 1117-1123
        • Dasenbrook EC
        • Merlo CA
        • Diener-West M
        • Lechtzin N
        • Boyle MP.
        Persistent methicillin-resistant staphylococcus aureus and rate of FEV1 decline in cystic fibrosis.
        Am J Respir Crit Care Med. 2008; 178: 814-821
        • Dasenbrook EC
        • Checkley W
        • Merlo CA
        • et al.
        Association between respiratory tract methicillin-resistant staphylococcus aureus and survival in cystic fibrosis.
        JAMA. 2010; 303: 2386-2392
        • Ballman M
        • Rabsch P
        • von der Hardt H
        Long term follow up of changes in FEV1 and treatment intensity during Pseudomonas aeruginosa colonisation in patients with cystic fibrosis.
        Thorax. 1998; 53: 732-737
        • Emerson J
        • Rosenfeld M
        • McNamara S
        • Ramsey B
        • Gibson RL.
        Pseudomonas aeruginosa and other predictors of mortality in young children with cystic fibrosis.
        Pediatr Pulmonol. 2002; 34: 91-100
        • Hoiby N.
        Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis.
        BMC Med. 2011; 9: 32
        • Knapp EA
        • Fink AK
        • Goss CH
        • et al.
        The cystic fibrosis foundation patient registry: design and methods of a national observational disease registry.
        Ann Am Thorac Soc. 2016; 13: 1173-1179
      3. Data source: pediatric health information systems database.
        Children's Hospital Association, Lenexa, KS2022 (Available at) (Accessed 7 March)
        • Cogen JD
        • Hall M
        • Loeffler DR
        • et al.
        Linkage of the cystic fibrosis foundation patient registry with the pediatric health information system database.
        Pediatr Pulmonol. 2018; 54: 721-728
        • Cogen JD
        • Faino AV
        • Onchiri F
        • Hall M
        • Fink AK.
        Evaluation of hospitalization data for the CFFPR-PHIS linked data set.
        Pediatr Pulmonol. 2020; 55: 30-32
        • Sanders DB
        • Bittner RC
        • Rosenfeld M
        • et al.
        Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation.
        Am J Respi Crit Care Med. 2010; 182: 627-632
      4. Sanford Guide. Antibacterial Spectra of Activity. Available at: Accessed 7 March 2022.

        • Cogen JD
        • Faino AV
        • Onchiri F
        • et al.
        Association between number of intravenous antipseudomonal antibiotics and clinical outcomes of pediatric cystic fibrosis pulmonary exacerbations.
        Clin Infect Dis. 2021; 73: 1589-1596
        • Cogen JD
        • Faino AV
        • Onchiri F
        • et al.
        Clinical outcomes of antipseudomonal versus other antibiotics among children with cystic fibrosis without Pseudomonas aeruginosa.
        Ann Am Thorac Soc. 2022; (Mar 15Online ahead of print)
        • Muhlebach MS.
        Methicillin-resistant Staphylococcus aureus in cystic fibrosis: how should it be managed?.
        Curr Opin Pulm Med. 2017; 23: 544-550
        • Limoli DH
        • Yan J
        • Khansaheb MK
        • et al.
        Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes.
        Eur J Clin Microbiol. 2016; 35: 947-953
        • Maliniak ML
        • Stecenko AA
        • McCarty NA.
        A longitudinal analysis of chronic MRSA and Pseudomonas aeruginosa co-infection in cystic fibrosis: a single-center study.
        J Cyst Fibros. 2016; 15: 256-350
        • Huber D
        • Reglier-Poupet H
        • Sermet-Gaudelus I
        • et al.
        Association between Staphylococcus aureus alone or combined with Pseudomonas aeruginosa and the clinical condition of patients with cystic fibrosis.
        J Cyst Fibros. 2013; 12: 497-503
        • Schwerdt M
        • Neumann C
        • Schwartbeck B
        • et al.
        Staphylococcus aureus in the airways of cystic fibrosis patients-A retrospective long-term study.
        Int J Med Microbiol. 2018; 308: 631-639
        • Desai RJ
        • Franklin JM.
        Alternative approaches for confounding adjustment in observational studies using weighting based on the propensity score: a primer for practitioners.
        BMJ. 2019; 367: I5657
        • Kahlert J
        • Gribsholt SB
        • Gammelager H
        • Dekkers OM
        • Luta G.
        Control of confounding in the analysis phase—an overview for clinicians.
        Clin Epidemiol. 2017; (0): 195-204
        • Courter JD
        • Parker SK
        • Thurm C
        • Kronman MP
        • Weissman SJ
        • Shah SS
        • Hersh AL
        • Brogan TV
        • Patel SJ
        • Smith MJ
        • Lee BR
        • Newland JG
        • Gerber JS.
        Accuracy of administrative data for antimicrobial administration in hospitalized children.
        J Pediatric Infect Dis Soc. 2018; 7: 261-263
        • Wagener JS
        • VanDevanter DR
        • Konstan MW
        • Pasta DJ
        • Millar SJ
        • Morgan WJ.
        Lung function changes before and after pulmonary exacerbation antimicrobial treatment in cystic fibrosis.
        Pediatr Pulmonol. 2020; 55: 828-834
        • Cogen JD
        • Kahl BC
        • Maples H
        • et al.
        Finding the relevance of antimicrobial stewardship for cystic fibrosis.
        J Cyst Fibros. 2020; 19: 511-520