{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:00:18Z","timestamp":1788278418424,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2017\u20102003"],"award-info":[{"award-number":["2017\u20102003"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased \u03b2\u2010lactam concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin\u2010tazobactam, in order to optimize the dosing regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective PK study included children with cancer, aged 1\u201317\u2009years, who were treated with piperacillin\u2010tazobactam for suspected or verified infection. A piperacillin\u2010tazobactam loading dose (100\u2009mg\/kg) was administered followed by continuous infusion (300\u2009mg\/kg\/day). The unbound fraction of piperacillin was quantified by high\u2010performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100%\n                      <jats:italic>f<\/jats:italic>\n                      T\u2009&gt;\u2009MIC) and 50%\n                      <jats:italic>f<\/jats:italic>\n                      T\u2009&gt;\u20094xMIC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 68 fever episodes among 38 children with a median (IQR) age of 6.5\u2009years and body weight of 27.4\u00a0kg (15.1\u201354.0). A three\u2010compartment model adequately described the concentration\u2010time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2\u00a0L\/h\/70\u2009kg (13.0; 15.3) and 47.6\u00a0mg\/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      breakpoint (16\u2009mg\/L) with the target of 100%\n                      <jats:italic>f<\/jats:italic>\n                      T\u2009&gt;\u2009MIC, and a daily dose of 300\u2009mg\/kg reached optimal PTA. The strict target of 50%\n                      <jats:italic>f<\/jats:italic>\n                      T\u2009&gt;\u20094xMIC (64\u2009mg\/L) was not feasibly attained by any dosing regimen at recommended doses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100%\n                      <jats:italic>f<\/jats:italic>\n                      T\u2009&gt;\u2009MIC to be reached for children with febrile neutropenia.\n                    <\/jats:p>\n                  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