{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T06:34:21Z","timestamp":1771914861859,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Cooperatio project (research area ONCO)"],"award-info":[{"award-number":["Cooperatio project (research area ONCO)"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Cooperatio project (research area PHAR)"],"award-info":[{"award-number":["Cooperatio project (research area PHAR)"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The objective of this study was to evaluate off\u2010label high\u2010dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug\u2010resistant (XDR) <jats:styled-content style=\"fixed-case\"><jats:italic>Pseudomonas aeruginosa<\/jats:italic><\/jats:styled-content> infections and then to compare the achievement of the pharmacokinetic\/pharmacodynamic (PK\/PD) target after standard and off\u2010label high\u2010dose regimens using population model\u2010based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off\u2010label high\u2010dose ceftazidime treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In patients treated with off\u2010label high\u2010dose ceftazidime (3\u2009g every 6\u00a0h), blood samples were collected and ceftazidime serum levels measured using LC\u2013MS\/MS. A pharmacokinetic population model was developed using a nonlinear mixed\u2010effects modelling approach and Monte Carlo simulations were then used to compare standard and high\u2010dose regimens for PK\/PD target attainment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 14 cancer patients with serious infection suspected of XDR <jats:styled-content style=\"fixed-case\"><jats:italic>P. aeruginosa<\/jats:italic><\/jats:styled-content> aetiology were eligible for PK analysis. XDR <jats:styled-content style=\"fixed-case\"><jats:italic>P. aeruginosa<\/jats:italic><\/jats:styled-content> was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23\u2009L, while clearance started at the baseline of 1.48\u2009L\/h and increased by 0.0076\u2009L\/h with each 1\u00a0mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup> of eGFR. High\u2010dose regimen showed significantly higher probability of target attainment (i.e., 86% <jats:italic>vs<\/jats:italic>. 56% at MIC of 32\u2009mg\/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We proved the superiority of the ceftazidime off\u2010label high\u2010dose regimen in PK\/PD target attainment with very low occurrence of adverse effects. The off\u2010label high\u2010dose regimen should be used to optimize treatment of XDR <jats:styled-content style=\"fixed-case\"><jats:italic>P. aeruginosa<\/jats:italic><\/jats:styled-content> infections.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15612","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T20:01:26Z","timestamp":1669320086000},"page":"1452-1461","source":"Crossref","is-referenced-by-count":6,"title":["Superiority of ceftazidime off\u2010label high\u2010dose regimen in PK\/PD target attainment during treatment of extensively drug\u2010resistant <scp><i>Pseudomonas aeruginosa<\/i><\/scp> infections in cancer patients"],"prefix":"10.1111","volume":"89","author":[{"given":"Alzbeta","family":"Zavrelova","sequence":"first","affiliation":[{"name":"4th Department of Internal Medicine \u2013 Hematology University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-738X","authenticated-orcid":false,"given":"Martin","family":"Sima","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Malakova","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry University Hospital Hradec Kralove and Charles University in Prague, Faculty of Medicine in Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Rozsivalova","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Hospital Pharmacy Faculty of Pharmacy in Hradec Kralove, Charles University and University Hospital Hradec Kralove  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavla","family":"Paterova","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Zak","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine \u2013 Hematology University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Visek","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine \u2013 Hematology University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danica","family":"Michalickova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ondrej","family":"Slanar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Radocha","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine \u2013 Hematology University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University  Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010198529020\u201000002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1L307"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010017\u20100578\u20102"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190015608503"},{"key":"e_1_2_10_6_1","unstructured":"State Institute for Drug Control of Czech Republic.Summary of product characteristics (ceftazidime). 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