Michael J Bozzella1, Hollis Chaney2,3, Iman Sami2,3, Anastassios Koumbourlis2,3, James E Bost3,4, Edith T Zemanick5, Robert J Freishtat3,6, Keith A Crandall7, Andrea Hahn1,3. 1. From the Division of Infectious Diseases, Children's National Hospital. 2. Division of Pulmonary and Sleep Medicine, Children's National Hospital. 3. The George Washington University School of Medicine and Health Sciences. 4. Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, District of Columbia. 5. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado. 6. Division of Emergency Medicine, Children's National Hospital. 7. Computational Biology Institute and Department of Biostatistics & Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, District of Columbia.
Abstract
BACKGROUND: The role of anaerobic organisms in the cystic fibrosis (CF) lung microbiome is unclear. Our objectives were to investigate the effect of broad (BS) versus narrow (NS) spectrum antianaerobic antibiotic activity on lung microbiome diversity and pulmonary function, hypothesizing that BS antibiotics would cause greater change in microbiome diversity without a significant improvement in lung function. METHODS: Pulmonary function tests and respiratory samples were collected prospectively in persons with CF before and after treatment for pulmonary exacerbations. Treatment antibiotics were classified as BS or NS. Gene sequencing data from 16S rRNA were used for diversity analysis and bacterial genera classification. We compared the effects of BS versus NS on diversity indices, lung function and anaerobic/aerobic ratios. Statistical significance was determined by multilevel mixed-effects generalized linear models and mixed-effects regression models. RESULTS: Twenty patients, 6-20 years of age, experienced 30 exacerbations. BS therapy had a greater effect on beta diversity than NS therapy when comparing time points before antibiotics to after and at recovery. After antibiotics, the NS therapy group had a greater return toward baseline forced expiratory volume at 1 second and forced expiratory flow 25%-75% values than the BS group. The ratio of anaerobic/aerobic organisms showed a predominance of anaerobes in the NS group with aerobes dominating in the BS group. CONCLUSIONS: BS antianaerobic therapy had a greater and possibly longer lasting effect on the lung microbiome of persons with CF, without achieving the recovery of pulmonary function seen with the NS therapy. Specific antibiotic therapies may affect disease progression by changing the airway microbiome.
BACKGROUND: The role of anaerobic organisms in the cystic fibrosis (CF) lung microbiome is unclear. Our objectives were to investigate the effect of broad (BS) versus narrow (NS) spectrum antianaerobic antibiotic activity on lung microbiome diversity and pulmonary function, hypothesizing that BS antibiotics would cause greater change in microbiome diversity without a significant improvement in lung function. METHODS: Pulmonary function tests and respiratory samples were collected prospectively in persons with CF before and after treatment for pulmonary exacerbations. Treatment antibiotics were classified as BS or NS. Gene sequencing data from 16S rRNA were used for diversity analysis and bacterial genera classification. We compared the effects of BS versus NS on diversity indices, lung function and anaerobic/aerobic ratios. Statistical significance was determined by multilevel mixed-effects generalized linear models and mixed-effects regression models. RESULTS: Twenty patients, 6-20 years of age, experienced 30 exacerbations. BS therapy had a greater effect on beta diversity than NS therapy when comparing time points before antibiotics to after and at recovery. After antibiotics, the NS therapy group had a greater return toward baseline forced expiratory volume at 1 second and forced expiratory flow 25%-75% values than the BS group. The ratio of anaerobic/aerobic organisms showed a predominance of anaerobes in the NS group with aerobes dominating in the BS group. CONCLUSIONS: BS antianaerobic therapy had a greater and possibly longer lasting effect on the lung microbiome of persons with CF, without achieving the recovery of pulmonary function seen with the NS therapy. Specific antibiotic therapies may affect disease progression by changing the airway microbiome.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: J Kirk Harris; Mary Ann De Groote; Scott D Sagel; Edith T Zemanick; Robert Kapsner; Churee Penvari; Heidi Kaess; Robin R Deterding; Frank J Accurso; Norman R Pace Journal: Proc Natl Acad Sci U S A Date: 2007-12-11 Impact factor: 11.205
Authors: James J Kozich; Sarah L Westcott; Nielson T Baxter; Sarah K Highlander; Patrick D Schloss Journal: Appl Environ Microbiol Date: 2013-06-21 Impact factor: 4.792
Authors: H J Fuchs; D S Borowitz; D H Christiansen; E M Morris; M L Nash; B W Ramsey; B J Rosenstein; A L Smith; M E Wohl Journal: N Engl J Med Date: 1994-09-08 Impact factor: 91.245
Authors: James F Chmiel; Timothy R Aksamit; Sanjay H Chotirmall; Elliott C Dasenbrook; J Stuart Elborn; John J LiPuma; Sarath C Ranganathan; Valerie J Waters; Felix A Ratjen Journal: Ann Am Thorac Soc Date: 2014-09
Authors: Bojana Mirković; Michelle A Murray; Gillian M Lavelle; Kevin Molloy; Ahmed Abdul Azim; Cedric Gunaratnam; Fiona Healy; Dubhfeasa Slattery; Paul McNally; Joe Hatch; Matthew Wolfgang; Michael M Tunney; Marianne S Muhlebach; Rosaleen Devery; Catherine M Greene; Noel G McElvaney Journal: Am J Respir Crit Care Med Date: 2015-12-01 Impact factor: 21.405
Authors: Katherine O'Neill; Judy M Bradley; Elinor Johnston; Stephanie McGrath; Leanne McIlreavey; Stephen Rowan; Alastair Reid; Ian Bradbury; Gisli Einarsson; J Stuart Elborn; Michael M Tunney Journal: PLoS One Date: 2015-05-20 Impact factor: 3.240
Authors: Andrea Hahn; Aszia Burrell; Hani Fanous; Hollis Chaney; Iman Sami; Geovanny F Perez; Anastassios C Koumbourlis; Robert J Freishtat; Keith A Crandall Journal: Heliyon Date: 2018-09-17
Authors: Andrea Hahn; Hani Fanous; Caroline Jensen; Hollis Chaney; Iman Sami; Geovanny F Perez; Anastassios C Koumbourlis; Stan Louie; James E Bost; John N van den Anker; Robert J Freishtat; Edith T Zemanick; Keith A Crandall Journal: Sci Rep Date: 2019-02-22 Impact factor: 4.379
Authors: Charles Kennedy; Isabella Greenberg; Geovanny F Perez; Hollis Chaney; Iman Sami; Folasade Ogunlesi; Anastassios C Koumbourlis; Benjamin Hammer; Rana F Hamdy; Jonathan D Cogen; Asha S Payne; Andrea Hahn Journal: Pediatr Pulmonol Date: 2022-02-04