{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:18:36Z","timestamp":1785417516278,"version":"3.56.0"},"reference-count":21,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100016956","name":"Melinta Therapeutics Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012807","name":"Midwestern University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI158530, R21AI174159"],"award-info":[{"award-number":["R01AI158530, R21AI174159"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Real-world meropenem-vaborbactam (MVB) pharmacokinetic-pharmacodynamic (PK\/PD) attainment data in patients with renal dysfunction including continuous renal replacement (CRRT) are lacking. We evaluated MVB PK in patients with renal dysfunction and CRRT. Patients requiring hemodialysis were excluded. Plasma concentrations were quantified using LC-MS\/MS. Multiple compartmental PK models and covariate effects were evaluated using Pmetrics 2.1.1. Free (f) fractions of 98% and 67% were assumed with targets of 40%\u2013 100%\n                      <jats:italic toggle=\"yes\">f<\/jats:italic>\n                      T\n                      <jats:sub>&gt;MIC<\/jats:sub>\n                      and\n                      <jats:italic toggle=\"yes\">f<\/jats:italic>\n                      AUC\/MIC &gt;38 for meropenem (MEM) and vaborbactam (VAB), respectively. Individual patient PK\/PD attainment was evaluated using Bayesian posterior predictions. Probability of target attainment (PTA) stratified by MIC and cumulative fraction of response (CFR) vs the EUCAST\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      distribution were evaluated for 2 and 4 g MVB regimens. Eighteen patients (54% female, 17% CRRT) aged 54 \u00b1 14 years, weighing 91 \u00b1 31 kg with a CrCL of 114 \u00b1 102 mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      at baseline, contributed 83 plasma samples. For each drug, a one-compartment PK model was identified. Non-CRRT and residual clearance of MEM was higher than VAB, resulting in VAB accumulation. Individual-patient target attainment was variable. MEM PTA was &gt;90% at MICs up to 0.5 mg\/L, and VAB PTA was &gt;90% at MICs up to 4 mg\/L across renal states. CFR for MEM was &gt;80%, and CFR for VAB was &gt;70% in patients with renal dysfunction or CRRT and standard PK\/PD targets with renal dosing regimens. For infections with MICs up to 1 mg\/L, MVB regimens of 2 g IV every 8 h were adequate in CRRT. Studies linking MVB attainment to clinical outcomes are needed.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00108-25","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T10:12:41Z","timestamp":1748859161000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetics of meropenem-vaborbactam in acutely ill hospitalized patients with various degrees of renal dysfunction including continuous renal replacement therapy"],"prefix":"10.1128","author":[{"given":"Griffin","family":"Reed","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, College of Pharmacy, Midwestern University","place":["Downers Grove, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4192-5229","authenticated-orcid":true,"given":"Adrian","family":"Valadez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, College of Pharmacy, Midwestern University","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University","place":["Downers Grove, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon J.","family":"Smith","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh, Division of Infectious Diseases","place":["Pittsburgh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-2225","authenticated-orcid":true,"given":"Erin K.","family":"McCreary","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh, Division of Infectious Diseases","place":["Pittsburgh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7167-6368","authenticated-orcid":false,"given":"Ellen G.","family":"Kline","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh, Division of Infectious Diseases","place":["Pittsburgh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MIchael N.","family":"Neely","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Keck School of Medicine, University of Southern California","place":["Los Angeles, USA"]},{"id":[{"id":"https:\/\/ror.org\/00412ts95","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute, Children\u2019s Hospital of Los Angeles","place":["Los Angeles, USA"]},{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh, School of Medicine","place":["Pittsburgh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Squires","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh, Division of Infectious Diseases","place":["Pittsburgh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-5665","authenticated-orcid":true,"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pittsburgh, Division of Infectious Diseases","place":["Pittsburgh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5434","authenticated-orcid":true,"given":"Nathaniel J.","family":"Rhodes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, College of Pharmacy, Midwestern University","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/009543z50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Northwestern Memorial Hospital","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"Vabomere [package insert]. 2017. The Medicines Company. Parsippany NJ 07054"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01659-18"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-018-0609-x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02606-20"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz103"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01306-18"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02497-17"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa139"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2378-9"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz1131"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_4_13_2","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM). 2018. Bioanalytical Method Validation Guidance for Industry Rockville MD"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-019-02184-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825c4ba6"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13010042"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02130-21"},{"key":"e_1_3_4_18_2","unstructured":"The European Committee on Antimicrobial Susceptibility Testing - EUCAST. 2025. Antimicrobial wild type distributions of microorganisms. Available from: https:\/\/mic.eucast.org\/search"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02048-18"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01520-08"},{"key":"e_1_3_4_21_2","unstructured":"US Food And Drug Administration Center for Drug Evaluation and Reseach. 2017 Clinical pharmacology review for vabomere. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2017\/209776Orig1s000ClinPharmR.pdf."},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1595"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00108-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00108-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T10:12:43Z","timestamp":1748859163000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00108-25"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":21,"alternative-id":["10.1128\/aac.00108-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00108-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"assertion":[{"value":"2025-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00108-25"}}