{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:13:42Z","timestamp":1790702022257,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI143671-01A1"],"award-info":[{"award-number":["R01 AI143671-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>People with cystic fibrosis (CF) routinely suffer from recurrent sinopulmonary infections. Such infections require frequent courses of antimicrobials and often involve multidrug-resistant organisms. The goal of this study was to identify real-world evidence for the effectiveness of elexacaftor-tezacaftor-ivacaftor (ELX\/TEZ\/IVA) in decreasing infection-related visits and antimicrobial use in people with CF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using IBM MarketScan data, we identified 389 enrollees with CF who began taking ELX\/TEZ\/IVA before 1 December 2019 and were enrolled from 1 July 2019 to 14 March 2020. We also identified a comparison population who did not begin ELX\/TEZ\/IVA during the study period. We compared the following outcomes in the 15 weeks before and after medication initiation: total healthcare visits, inpatient visits, infection-related visits, and antimicrobial prescriptions. We analyzed outcomes using both a case-crossover analysis and a difference-in-differences analysis, to control for underlying trends.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For the case-crossover analysis, ELX\/TEZ\/IVA initiation was associated with the following changes over a 15-week period: change in overall healthcare visit dates, \u22122.5 (95% confidence interval, \u22123.31 to \u22121.7); change in inpatient admissions, \u22120.16 (\u2212.22 to \u2212.10); change in infection-related visit dates, \u22120.62 (\u2212.93 to \u2212.31); and change in antibiotic prescriptions, \u22120.78 (\u22121.03 to \u2212.54). Results from the difference-in-differences approach were similar.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We show a rapid reduction in infection-related visits and antimicrobial use among people with CF after starting a therapy that was not explicitly designed to treat infections. Currently, there are &amp;gt;30\u00a0000 people living with CF in the United States alone. Given that this therapy is effective for approximately 90% of people with CF, the impact on respiratory infections and antimicrobial use may be substantial.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac117","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T20:11:51Z","timestamp":1644264711000},"page":"1115-1122","source":"Crossref","is-referenced-by-count":48,"title":["The Rapid Reduction of Infection-Related Visits and Antibiotic Use Among People With Cystic Fibrosis After Starting Elexacaftor-Tezacaftor-Ivacaftor"],"prefix":"10.1093","volume":"75","author":[{"given":"Aaron C","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan M","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E","family":"Cavanaugh","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Abou Alaiwa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B","family":"Hornick","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M","family":"Polgreen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"2022093020233259800_CIT0001","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrg3849","article-title":"Cystic fibrosis genetics: from molecular understanding to clinical application.","volume":"16","author":"Cutting","year":"2015","journal-title":"Nat Rev Genet"},{"key":"2022093020233259800_CIT0002","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis.","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"2022093020233259800_CIT0003","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMra1300109","article-title":"Origins of cystic fibrosis lung disease.","volume":"372","author":"Stoltz","year":"2015","journal-title":"N Engl J Med"},{"key":"2022093020233259800_CIT0004","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1513\/AnnalsATS.201401-034OI","article-title":"Is there a role for antimicrobial stewardship in cystic fibrosis?","volume":"11","author":"Waters","year":"2014","journal-title":"Ann Am Thorac Soc"},{"key":"2022093020233259800_CIT0005","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/CPM.0000000000000370","article-title":"Antibiotic use and stewardship in cystic fibrosis: a review for noncystic fibrosis providers.","volume":"27","author":"Orsini","year":"2020","journal-title":"Clin Pulm Med"},{"key":"2022093020233259800_CIT0006","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1128\/CMR.00068-09","article-title":"The changing microbial epidemiology in cystic fibrosis.","volume":"23","author":"Lipuma","year":"2010","journal-title":"Clin Microbiol Rev"},{"key":"2022093020233259800_CIT0007","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1378\/chest.09-0132","article-title":"Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005.","volume":"136","author":"Razvi","year":"2009","journal-title":"Chest"},{"key":"2022093020233259800_CIT0008","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0140-6736(14)61137-5","article-title":"Antimicrobial resistance in the respiratory microbiota of people with cystic fibrosis.","volume":"384","author":"Sherrard","year":"2014","journal-title":"Lancet"},{"key":"2022093020233259800_CIT0009","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1055\/s-0039-1698464","article-title":"Microbiology of cystic fibrosis airway disease.","volume":"40","author":"Blanchard","year":"2019","journal-title":"Semin Respir Crit Care Med"},{"key":"2022093020233259800_CIT0010","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1164\/rccm.201307-1200OC","article-title":"Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis.","volume":"188","author":"Binder","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2022093020233259800_CIT0011","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ccm.2015.11.001","article-title":"Nontuberculous mycobacterial infections in cystic fibrosis.","volume":"37","author":"Martiniano","year":"2016","journal-title":"Clin Chest Med"},{"key":"2022093020233259800_CIT0012","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.jcf.2012.07.005","article-title":"An overview of international literature from cystic fibrosis registries. Part 4: update 2011.","volume":"11","author":"Salvatore","year":"2012","journal-title":"J Cyst Fibros"},{"key":"2022093020233259800_CIT0013","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1183\/09031936.00119714","article-title":"A contemporary survival analysis of individuals with cystic fibrosis: a cohort study.","volume":"45","author":"Stephenson","year":"2015","journal-title":"Eur Respir J"},{"key":"2022093020233259800_CIT0014","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1097\/MCP.0000000000000520","article-title":"Cystic fibrosis survival: the changing epidemiology.","volume":"24","author":"Corriveau","year":"2018","journal-title":"Curr Opin Pulm Med"},{"key":"2022093020233259800_CIT0015","article-title":"The changing epidemiology of cystic fibrosis: incidence, survival and impact of the CFTR gene discovery.","volume":"11:589","author":"Scotet","year":"2020","journal-title":"Genes (Basel)"},{"key":"2022093020233259800_CIT0016","article-title":"Understanding changes in life expectancy: survival statistics for the years 2015 through 2019.","author":"Cystic Fibrosis Foundation."},{"key":"2022093020233259800_CIT0017","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jcf.2020.07.017","article-title":"Projecting the impact of delayed access to elexacaftor\/tezacaftor\/ivacaftor for people with cystic fibrosis.","volume":"20","author":"Stanojevic","year":"2021","journal-title":"J Cyst Fibros"},{"key":"2022093020233259800_CIT0018","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","article-title":"A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.","volume":"365","author":"Ramsey","year":"2011","journal-title":"N Engl J Med"},{"key":"2022093020233259800_CIT0019","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2147\/CEOR.S162021","article-title":"The burden of cystic fibrosis in the Medicaid population.","volume":"10","author":"Hassan","year":"2018","journal-title":"Clinicoecon Outcomes Res"},{"key":"2022093020233259800_CIT0020","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3111\/13696998.2011.638954","article-title":"Economic burden of Pseudomonas aeruginosa infection in patients with cystic fibrosis.","volume":"15","author":"Sansgiry","year":"2012","journal-title":"J Med Econ"},{"key":"2022093020233259800_CIT0021","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s40258-013-0027-z","article-title":"Economic burden of non-cystic fibrosis bronchiectasis in the first year after diagnosis from a US health plan perspective.","volume":"11","author":"Joish","year":"2013","journal-title":"Appl Health Econ Health Policy"},{"key":"2022093020233259800_CIT0022","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2147\/PPA.S134759","article-title":"Adherence to tobramycin inhaled powder vs inhaled solution in patients with cystic fibrosis: analysis of US insurance claims data.","volume":"11","author":"Hamed","year":"2017","journal-title":"Patient Prefer Adher"},{"key":"2022093020233259800_CIT0023","doi-asserted-by":"crossref","DOI":"10.14309\/ajg.0000000000001527","article-title":"Cystic fibrosis transmembrane conductance regulator modulator use is associated with reduced pancreatitis hospitalizations in patients with cystic fibrosis.","author":"Ramsey","year":"2021; 116:2446\u201354","journal-title":"Am J Gastroenterol"},{"key":"2022093020233259800_CIT0024","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1073\/pnas.1914912117","article-title":"Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions.","volume":"117","author":"Miller","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022093020233259800_CIT0025","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1377\/hlthaff.2017.1554","article-title":"Precision medicine in action: the impact of ivacaftor on cystic fibrosis-related hospitalizations.","volume":"37","author":"Feng","year":"2018","journal-title":"Health Aff (Millwood)"},{"key":"2022093020233259800_CIT0026","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1080\/03007995.2016.1277196","article-title":"Frequency and costs of pulmonary exacerbations in patients with cystic fibrosis in the United States.","volume":"33","author":"Rubin","year":"2017","journal-title":"Curr Med Res Opin"},{"key":"2022093020233259800_CIT0027","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1515\/sagmb-2013-0066","article-title":"Robustness of the linear mixed effects model to error distribution assumptions and the consequences for genome-wide association studies.","volume":"13","author":"Warrington","year":"2014","journal-title":"Stat Appl Genet Mol Biol"},{"key":"2022093020233259800_CIT0028","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/2041-210X.13434","article-title":"Robustness of linear mixed-effects models to violations of distributional assumptions.","volume":"11","author":"Schielzeth","year":"2020","journal-title":"Methods Ecol Evol"},{"key":"2022093020233259800_CIT0029","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jcf.2014.02.004","article-title":"Antibacterial properties of the CFTR potentiator ivacaftor.","volume":"13","author":"Reznikov","year":"2014","journal-title":"J Cyst Fibros"},{"key":"2022093020233259800_CIT0030","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.ijantimicag.2017.03.020","article-title":"Repurposing ivacaftor for treatment of Staphylococcus aureus infections.","volume":"50","author":"Thakare","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"2022093020233259800_CIT0031","doi-asserted-by":"crossref","first-page":"18703","DOI":"10.1073\/pnas.1422091112","article-title":"pH modulates the activity and synergism of the airway surface liquid antimicrobials \u03b2-defensin-3 and LL-37.","volume":"111","author":"Abou Alaiwa","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022093020233259800_CIT0032","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1513\/AnnalsATS.201902-122OC","article-title":"Ivacaftor is associated with reduced lung infection by key cystic fibrosis pathogens. A cohort study using national registry data.","volume":"16","author":"Frost","year":"2019","journal-title":"Ann Am Thorac Soc"},{"key":"2022093020233259800_CIT0033","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1164\/rccm.201609-1954OC","article-title":"Restoring cystic fibrosis transmembrane conductance regulator function reduces airway bacteria and inflammation in people with cystic fibrosis and chronic lung infections.","volume":"195","author":"Hisert","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2022093020233259800_CIT0034","article-title":"Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR.","volume":"3:e122695","author":"Donaldson","year":"2018","journal-title":"JCI Insight"},{"key":"2022093020233259800_CIT0035","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele.","volume":"381","author":"Middleton","year":"2019","journal-title":"N Engl J Med"},{"key":"2022093020233259800_CIT0036","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/cpt.2474","article-title":"The role of real-world evidence in FDA-approved new drug and biologics license applications.","volume":"111","author":"Purpura","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"2022093020233259800_CIT0037","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1002\/pds.4962","article-title":"Use of real-world evidence in regulatory decisions for rare diseases in the United States-Current status and future directions.","volume":"29","author":"Wu","year":"2020","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022093020233259800_CIT0038","first-page":"ofy219","article-title":"CFTR heterozygotes are at increased risk of respiratory infections: a population-based study.","volume-title":"Open Forum Infect Dis","author":"Polgreen","year":"2018"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac117\/43374613\/ciac117.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/7\/1115\/46227267\/ciac117.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/7\/1115\/46227267\/ciac117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T20:29:55Z","timestamp":1664569795000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/75\/7\/1115\/6526243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,10]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,2,10]]},"published-print":{"date-parts":[[2022,9,30]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac117","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10,1]]},"published":{"date-parts":[[2022,2,10]]}}}