{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T23:59:28Z","timestamp":1725148768288},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,2]],"date-time":"2022-10-02T00:00:00Z","timestamp":1664668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ASPECT\u2010NP, a phase 3 trial of ceftolozane\/tazobactam in hospital\u2010acquired\/ventilator\u2010associated bacterial pneumonia (HABP\/VABP), excluded patients with end\u2010stage renal disease (ESRD). A modeling\/simulation approach was undertaken to inform optimal dosing in this population, using previously developed ceftolozane and tazobactam population pharmacokinetic models informed by data from 16 clinical studies. Stochastic simulations were performed using NONMEM to support dose justification. Probability of target attainment (PTA) simulations in plasma and epithelial lining fluid were conducted using a 14\u2010day treatment, with hemodialysis every other weekday for a high\u2010dose (4X), middle\u2010dose (3X), or low\u2010dose (2X) regimen, where X was the recommended dose in patients with complicated intra\u2010abdominal infection\/complicated urinary tract infection and ESRD (500 mg\/250 mg ceftolozane\/tazobactam loading dose and 100 mg\/50 mg ceftolozane\/tazobactam maintenance dose administered by 1\u2010hour infusion every 8 hours). PTA was determined using established pharmacokinetic\/pharmacodynamic targets: ceftolozane, 30% of the interdose interval (8 hours) in which free ceftolozane concentration exceeded the minimum inhibitory concentration value of 4\u00a0\u00b5g\/mL; tazobactam, 20% of the interdose interval in which free tazobactam concentration exceeded 1\u00a0\u00b5g\/mL. Plasma PTA was &gt;90% for both agents for all 3 regimens. Plasma ceftolozane exposures at the high\u2010dose regimen exceeded those from phase 3 study experience. Epithelial lining fluid PTA was &gt;90% for high\u2010 and middle\u2010dose regimens but was &lt;80% for tazobactam on dialysis days at the low\u2010dose regimen. For patients with HABP\/VABP and ESRD requiring intermittent hemodialysis, the middle\u2010dose regimen of 1.5 g\/0.75 g ceftolozane\/tazobactam loading + 300 mg\/150 mg maintenance every 8 hours by 1\u2010hour infusion is recommended.<\/jats:p>","DOI":"10.1002\/jcph.2149","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T06:58:49Z","timestamp":1662015529000},"page":"166-171","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Probability of Target Attainment Analyses to Inform Ceftolozane\/Tazobactam Dosing Regimens for Patients With Hospital\u2010Acquired or Ventilator\u2010Associated Bacterial Pneumonia and End\u2010Stage Renal Disease Receiving Intermittent Hemodialysis"],"prefix":"10.1002","volume":"63","author":[{"given":"Hwa\u2010Ping","family":"Feng","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yogesh T.","family":"Patel","sequence":"additional","affiliation":[{"name":"Cognigen Corporation, a Simulations Plus Company  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zufei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Fiedler\u2010Kelly","sequence":"additional","affiliation":[{"name":"Cognigen Corporation, a Simulations Plus Company  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth G.","family":"Rhee","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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