{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:19:45Z","timestamp":1788239985844,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ILLAMO20A0\u2010I"],"award-info":[{"award-number":["ILLAMO20A0\u2010I"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Acute pulmonary exacerbations (APE) in persons with cystic fibrosis (PwCF) are associated with a reduction in long\u2010term pulmonary function. Vancomycin is recommended as first\u2010line treatment of methicillin\u2010resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      \u2010APE in PwCF. While vancomycin poses a significant risk of nephrotoxicity, the relationship between vancomycin exposure and nephrotoxicity in PwCF has not been characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to establish the relationship between vancomycin exposure and onset of nephrotoxicity in PwCF, and to identify predictors of nephrotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective study among 52 adults PwCF. Nephrotoxicity events were defined based on the RIFLE criteria, as a serum creatinine increase of 1.5 times from baseline or a\u2009\u2265\u200925% decrease in glomerular filtration rate. A population pharmacokinetic (popPK) model was used to derive exposure measures (i.e., area\u2010under the concentration\u2010time curve (AUC)).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 590 vancomycin serum concentrations were available for analysis. A one\u2010compartment model best describes vancomycin pharmacokinetics. Creatinine clearance was included as a significant covariate in the clearance. The popPK model allowed quantification of cumulative AUC (AUC\n                      <jats:sub>cum<\/jats:sub>\n                      ) and AUC\n                      <jats:sub>24<\/jats:sub>\n                      values, and AUC normalized (AUC\n                      <jats:sub>norm<\/jats:sub>\n                      ) and cumulative dose were further calculated. Each variable of interest was used to fit a generalized linear mixed\u2010effects (GLM) model. The GLM model identified AUC\n                      <jats:sub>cum<\/jats:sub>\n                      as a significant predictor of vancomycin nephrotoxicity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Additionally, patients with more than one dosing occasion were significantly more likely to experience nephrotoxicity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Based on the final AUC\n                      <jats:sub>cum<\/jats:sub>\n                      model, the odds of experiencing a nephrotoxicity event increased by 32.6% (95% CI: 11.0%\u201358.4%) for each doubling of AUC\n                      <jats:sub>cum<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results demonstrate an association between increased vancomycin exposures and risk of nephrotoxicity. This study provides a foundation for optimizing personalized vancomycin dosing strategies in PwCF to balance efficacy and nephrotoxicity risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71748","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:35:59Z","timestamp":1785191759000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic and Exposure\u2010Response Analysis of Vancomycin Nephrotoxicity in Cystic Fibrosis Patients"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-5650","authenticated-orcid":false,"given":"Jessica","family":"Barry","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-7314","authenticated-orcid":false,"given":"J. G. C.","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Leiden University Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7449-3993","authenticated-orcid":false,"given":"Michael","family":"Evans","sequence":"additional","affiliation":[{"name":"Clinical and Translational Science Institute University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-0421","authenticated-orcid":false,"given":"Elizabeth B.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Dunitz","sequence":"additional","affiliation":[{"name":"The Minnesota Cystic Fibrosis Center, Department of Medicine University of Minnesota School of Medicine Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Shockley","sequence":"additional","affiliation":[{"name":"The Minnesota Cystic Fibrosis Center, Department of Medicine University of Minnesota School of Medicine Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Billings","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3245-1626","authenticated-orcid":false,"given":"S\u00edlvia M.","family":"Illamola","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.121.1.64"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00006512"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200802-327OC"},{"key":"e_1_2_11_5_1","unstructured":"Patient Registry | Cystic Fibrosis Foundation accessed May 7 2024 https:\/\/www.cff.org\/medical-professionals\/patient-registry."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.15-0676"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:82532"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812-1845PP"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201402-050AS"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028014567526"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxaa036"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028015594190"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028014549185"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X1504300507"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn203"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.08.019"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piu110"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/pit076"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.060889"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01684-17"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00067-19"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342050-00007"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12015"},{"issue":"6","key":"e_1_2_11_24_1","first-page":"743","article-title":"Drug\u2010Induced Nephrotoxicity","volume":"78","author":"Naughton C. A.","year":"2008","journal-title":"American Family Physician"},{"key":"e_1_2_11_25_1","volume-title":"Estimating Glomerular Filtration Rate \u2010 NIDDK"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.1.186"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00866-2"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1320"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc2872"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.726"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179548420930925"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26077"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00992-23"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01568-12"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01602-07"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2010.07.025"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00173-11"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.166.19.2138"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.71748","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ppul.71748","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.71748","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:04:37Z","timestamp":1788239077000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.71748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":38,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ppul.71748"],"URL":"https:\/\/doi.org\/10.1002\/ppul.71748","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"2025-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71748"}}