{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:38:39Z","timestamp":1788986319649,"version":"build-2803163510"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,11,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Ceftolozane\/tazobactam is a key antibiotic for\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      infections. Our objective was to determine whether continuous infusion (CI) of ceftolozane\/tazobactam can achieve aggressive pharmacokinetic\/pharmacodynamic (PK\/PD) targets that suppress resistance and improve outcomes in severe\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      infections. A retrospective analysis of adult patients receiving CI ceftolozane\/tazobactam and therapeutic drug monitoring (TDM) of both compounds was performed. Population PK\/PD modeling identified the most accurate method for estimating ceftolozane\/tazobactam clearance based on kidney function and Monte Carlo simulations investigated the relationship between various CI dosing regimens and aggressive PK\/PD target attainment of ceftolozane\/tazobactam. The 2021 non-race-based Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) equation with body surface area indexation provided the most reliable clearance estimates. Simulations showed that CI regimens of 4\u20136 g\/2\u20133 g daily achieved optimal target attainment (\u226590%) across all kidney function strata for MICs up to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint. Cumulative fraction of responses remained robust against key resistance phenotypes: MDR (12.6%; 83.8%), pan-beta-lactam-nonsusceptible (8.2%; 78.2%), and difficult-to-treat resistant (6.7%; 71.7%). Even among isolates with MIC &gt;4 mg\/L, aggressive target attainment was reached in 15%\u201340% of cases. This study suggests that CI ceftolozane\/tazobactam, informed by TDM and optimized for aggressive PK\/PD targets, offers a promising strategy to maximize efficacy and suppress resistance in severe\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      infections. These findings warrant prospective clinical trials of CI-based, exposure-guided therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01042-25","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:00:21Z","timestamp":1758542421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Targeting\n                    <i>Pseudomonas aeruginosa<\/i>\n                    resistance at the exposure frontier: a population PK\/PD blueprint for ceftolozane\/tazobactam continuous infusion"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-4410","authenticated-orcid":true,"given":"Pier Giorgio","family":"Cojutti","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna","place":["Bologna, Italy"]},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":true,"given":"Milo","family":"Gatti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna","place":["Bologna, Italy"]},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna","place":["Bologna, Italy"]},{"name":"Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Tonetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna","place":["Bologna, Italy"]},{"name":"Anesthesiology and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Siniscalchi","sequence":"additional","affiliation":[{"name":"Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna","place":["Bologna, Italy"]},{"name":"Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-7167","authenticated-orcid":true,"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna","place":["Bologna, Italy"]},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000981"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00648-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaf098"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2017.06.007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02291-19"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1733"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01265-19"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-024-04911-5"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00189-22"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1542491"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1306"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00892-22"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001334"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001236"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01737-10"},{"key":"e_1_3_3_18_2","unstructured":"Anonymous. European Committee on Antimicrobial Susceptibility Testing. 2019. European Committee on Antimicrobial Susceptibility Testing. Ceftolozane\/Tazobactam: Rationale for the Clinical Breakpoints Version 1.0. Available from: http:\/\/www.eucast.org"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1609"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01042-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01042-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:06:24Z","timestamp":1785884784000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01042-25"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,5]]}},"alternative-id":["10.1128\/aac.01042-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01042-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"assertion":[{"value":"2025-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01042-25"}}