{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:12:04Z","timestamp":1768608724438,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006415","name":"Ben B. and Iris M. Margolis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006415","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Claudia Ruth Goodrich Stevens Endowment Fund"},{"DOI":"10.13039\/100007747","name":"University of Utah","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"US Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["(CC132-16AD"],"award-info":[{"award-number":["(CC132-16AD"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"US Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["CC132-17AD"],"award-info":[{"award-number":["CC132-17AD"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"US National Institutes of Health","doi-asserted-by":"publisher","award":["HL125520"],"award-info":[{"award-number":["HL125520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cystic fibrosis (CF) pulmonary exacerbations shorten survival. Treatment guidelines omit minimal inhibitory concentration (MIC)\u2013based antibiotic dose selection. We tested whether MIC-guided intravenous antibiotic strategies prolong time between exacerbations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively studied randomly chosen intravenous antibiotic\u2013treated pulmonary exacerbations from 2015 to 2018, followed through 2021. Using pre-admission sputum culture\u2013derived MICs to select dosing targets, we estimated measured:target ratios for \u03b2-lactam steady-state and aminoglycoside area under the curve pharmacokinetics. We used Kaplan-Meier and Cox proportional hazards methods to test whether measured:target ratios were associated with time to next exacerbation. We evaluated serial laboratory measurements with linear mixed-effects models for adverse events. We tested model sensitivities to concurrent treatments and severe acute respiratory syndrome coronavirus 2 pandemic\u2013related events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with measured:target ratios \u22641, \u03b2-lactam ratios &amp;gt;1 were associated with a median of 19 more (from 204 to 223) exacerbation-free days (91 exacerbations; hazard ratio [HR], 0.60; 95% CI, 0.37\u20130.99; P = .045); aminoglycoside ratios &amp;gt;1 were associated with a median of 83 more (from 153 to 236) exacerbation-free days (65 exacerbations; HR, 0.54; 95% CI, 0.31\u20130.93; P = .026); both antibiotic ratios &amp;gt;1 simultaneously were associated with a median of 210 more (from 185 to 396) exacerbation-free days (60 exacerbations; HR, 0.33; 95% CI, 0.15\u20130.71; P = .004). No toxic antibiotic levels and few adverse laboratory or clinical events occurred. Models were insensitive to other treatments and pandemic events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MIC-guided antibiotic dosing prolongs time between pulmonary exacerbations with few adverse events. Reduced exacerbation frequency predicts better survival and may improve quality of life for people with CF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofaf745","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:57:45Z","timestamp":1765025865000},"source":"Crossref","is-referenced-by-count":0,"title":["An Observational Cohort Study of Targeted Antibiotic Treatments of Cystic Fibrosis Exacerbations"],"prefix":"10.1093","volume":"13","author":[{"given":"HollyAnn R","family":"Jacobs","sequence":"first","affiliation":[{"name":"Adult Cystic Fibrosis Center, University of Utah Health , Salt Lake City, Utah ,","place":["USA"]},{"name":"Department of Pharmacotherapy, School of Pharmacy, University of Utah , Salt Lake City, Utah ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2151-1711","authenticated-orcid":false,"given":"Kristyn 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D","family":"Szczesniak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Divisions of Biostatistics & Epidemiology and Pulmonary Medicine, Cincinnati Children's Hospital and University of Cincinnati , Cincinnati, Ohio ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Utah , Salt Lake City, Utah ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3832-9536","authenticated-orcid":false,"given":"Warren E","family":"Regelmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Pulmonary and Sleep Medicine, Emeritus, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-7257","authenticated-orcid":false,"given":"David C","family":"Young","sequence":"additional","affiliation":[{"name":"Adult Cystic Fibrosis Center, University of Utah Health , Salt Lake City, Utah ,","place":["USA"]},{"name":"Department of Pharmacotherapy, School of Pharmacy, University of Utah , Salt Lake City, Utah ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-4847","authenticated-orcid":false,"given":"Theodore G","family":"Liou","sequence":"additional","affiliation":[{"name":"Adult Cystic Fibrosis Center, University of Utah Health , Salt Lake City, Utah ,","place":["USA"]},{"name":"Department of Internal Medicine, Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, School of Medicine, University of Utah , Salt Lake City, Utah ,","place":["USA"]},{"name":"The Center for 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