{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:42:39Z","timestamp":1788471759412,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012807","name":"Midwestern University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Meropenem is widely used to treat hospital\u2010acquired pneumonia in critically ill patients, with efficacy dependent on the time that free concentrations exceed the minimum inhibitory concentration (\n                      <jats:italic>f<\/jats:italic>\n                      T &gt; MIC). In practice, single\u2010sample therapeutic drug monitoring (TDM) may not ensure target attainment, particularly in patients requiring continuous renal replacement (CRRT). Model\u2010informed precision dosing (MIPD) enables individualized, real\u2010time adjustments, but implementation is limited. Herein, we developed a Shiny application for Bayesian meropenem dose optimization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A previously published nonparametric model was translated into a parametric Bayesian framework with maximum a posteriori (MAP) updating implemented through a Shiny interface. Plasma pharmacokinetic (PK) data from critically ill patients served for external validation. Posterior predictions were benchmarked against population and individual (MAP) outputs from Pmetrics 3.09 and population median profiles from 1000 Monte Carlo simulations per patient. Predictive performance was assessed using relative median prediction error (\n                      <jats:italic>r<\/jats:italic>\n                      MPE) and relative median absolute prediction error (\n                      <jats:italic>r<\/jats:italic>\n                      MAPE), for the combined cohort overall and stratified by CRRT status. Sparse sampling scenarios (one, two, and three observations per patient) were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighteen patients were evaluated (non\u2010CRRT\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913; CRRT\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095). In Pmetrics,\n                      <jats:italic>r<\/jats:italic>\n                      MPE ranged from \u22127.7% to 9.4% and\n                      <jats:italic>r<\/jats:italic>\n                      MAPE from 18.5% to 25.5% across renal replacement strata and prediction types. Simulation\u2010based population predictions yielded greater error, with\n                      <jats:italic>r<\/jats:italic>\n                      MPE\/\n                      <jats:italic>r<\/jats:italic>\n                      MAPE of \u221225%\/34% in CRRT patients and \u221221%\/30% in non\u2010CRRT patients. Across Bayesian Dosing Simulator (BDS) sampling scenarios, prediction error remained within prespecified limits (\n                      <jats:italic>r<\/jats:italic>\n                      MPE \u00b120%,\n                      <jats:italic>r<\/jats:italic>\n                      MAPE \u2264\u200930%), with F20 ranging from 80% to 94% and F30 from 87% to 94%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A validated nonparametric meropenem model was successfully implemented within an open\u2010source Bayesian framework yielding predictive accuracy comparable to the reference model with robust performance under sparse sampling, supporting its feasibility for individualized meropenem dosing. Prospective evaluation of its clinical safety and effectiveness is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70148","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:51:05Z","timestamp":1777528265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bayesian Dosing Simulator (\n                    <scp>BDS<\/scp>\n                    ): A Pharmacokinetic Modeling Tool for Optimized Antibiotic Therapy"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4192-5229","authenticated-orcid":false,"given":"Adrian","family":"Valadez","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice Midwestern University, College of Pharmacy  Downers Grove Illinois USA"},{"name":"Pharmacometrics Center of Excellence Midwestern University  Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-6130","authenticated-orcid":false,"given":"Marc H.","family":"Scheetz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Midwestern University, College of Pharmacy  Downers Grove Illinois USA"},{"name":"Pharmacometrics Center of Excellence Midwestern University  Downers Grove Illinois USA"},{"name":"Department of Pharmacy Northwestern Memorial Hospital  Chicago Illinois USA"},{"name":"Departments of Pharmacology and Biomedical Sciences, College of Graduate Studies Midwestern University  Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-8276","authenticated-orcid":false,"given":"Michael N.","family":"Neely","sequence":"additional","affiliation":[{"name":"Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics The Saban Research Institute, Children's Hospital of Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-8581","authenticated-orcid":false,"given":"Helen K.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3853-3219","authenticated-orcid":false,"given":"Erin","family":"Korth","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8527-4195","authenticated-orcid":false,"given":"Richard G.","family":"Wunderink","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5434","authenticated-orcid":false,"given":"Nathaniel J.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Midwestern University, College of Pharmacy  Downers Grove Illinois USA"},{"name":"Pharmacometrics Center of Excellence Midwestern University  Downers Grove Illinois USA"},{"name":"Department of Pharmacy Northwestern Memorial Hospital  Chicago Illinois 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