{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:30Z","timestamp":1790621910391,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Meropenem is a second\u2010line antimicrobial agent in the treatment of febrile neutropenia in onco\u2010haematological patients. A population pharmacokinetic\/pharmacodynamic (PK\/PD) analysis for assessing the relationship between meropenem exposure and C\u2010reactive protein (C\u2010RP) over time was conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Non\u2010linear mixed\u2010effect modelling was used to fit meropenem and C\u2010RP concentrations. Monte Carlo simulations were conducted to assess median percentage reduction of C\u2010RP from baseline associated with continuous infusion meropenem dosing, ensuring optimal PK\/PD target attainment against\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      <\/jats:styled-content>\n                      and\n                      <jats:italic>Enterobacterales<\/jats:italic>\n                      , namely, 100%\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>&gt;4\u2009\u00d7\u2009MIC<\/jats:sub>\n                      . Clinical outcome was assessed at the end of antimicrobial treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 141 patients were included in the analysis. A one\u2010compartment model with estimated glomerular filtration rate as a covariate on drug clearance well\u2010described meropenem pharmacokinetics. An indirect turnover maximum inhibition model was used to capture C\u2010RP dynamics. Patients with C\u2010RP Day 4\/baseline ratio of &lt;0.4 (fast response), between 0.4 and 0.8 (slow response) and &gt;0.8 (no response) were 8.5%, 15.6% and 75.9%, respectively. Regression analysis showed that patients with fast and slow response patterns were associated with favourable clinical outcomes. Simulations showed that rapid and slow pattern patients reached C\u2010RP reduction &gt;90% from baseline at Days 6 and 10, respectively. No response pattern had C\u2010RP peaking at Day 3 and eventually gradually reducing within 2\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite optimal meropenem PK\/PD target attainment, C\u2010RP decreases in no more than one\u2010fourth of onco\u2010haematological patients during the first 2\u2009weeks of treatment. Among no\u2010response patients, C\u2010RP should be associated with other biomarkers to discriminate subjects with favourable clinical outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70667","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:44:14Z","timestamp":1783053854000},"page":"3646-3655","source":"Crossref","is-referenced-by-count":0,"title":["Relationship between continuous infusion meropenem PK\/PD target attainment and C\u2010reactive protein dynamics in onco\u2010haematologic patients with febrile neutropenia"],"prefix":"10.1002","volume":"92","author":[{"given":"Chun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-4410","authenticated-orcid":false,"given":"Pier Giorgio","family":"Cojutti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences Alma Mater Studiorum, University of Bologna  Bologna Italy"},{"name":"Clinical Pharmacology Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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