{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:35:27Z","timestamp":1772645727986,"version":"3.50.1"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      An exposure\u2013efficacy analysis of the phase 3 RESTORE-IMI 2 study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02493764\" xlink:type=\"simple\">NCT02493764<\/jats:ext-link>\n                      ) evaluated the relationship between plasma exposure of imipenem and relebactam and key efficacy endpoints (primary: 28-day all-cause mortality [ACM]; secondary: clinical response at early follow-up [EFU; 7\u201314 days after the end of treatment]) in adult participants with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) who received imipenem\/cilastatin\/relebactam 500\/500\/250 mg (IMI\/REL). Participants from the IMI\/REL treatment group in the microbiological-modified intent-to-treat population who had pharmacokinetic (PK) data and relevant baseline pathogen susceptibility data available were included (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      = 211). Previously developed population PK models were used to derive steady-state imipenem and relebactam exposures. Exposures were analyzed against the primary and secondary endpoints overall and by the most common key pathogens identified during RESTORE-IMI 2 (\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Acinetobacter calcoaceticus\u2013baumannii<\/jats:italic>\n                      complex, and\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      ). Most participants (82.0%;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 168\/205) achieved the imipenem exposure target, and 83.9% (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 177\/211) achieved the relebactam exposure target. ACM was 16.1% overall; 11% among participants who met the imipenem exposure target, and 18% among those who met the relebactam exposure target. At EFU, 62.1% of participants experienced a favorable clinical response. Efficacy was similar across the overall exposure range and by key pathogens. There were no apparent trends in ACM rates by imipenem or relebactam exposure distributions overall or by individual key pathogens, suggesting an exposure\u2013efficacy plateau. These results further support the recommended and currently approved IMI\/REL 500\/500\/250 mg dosing regimen for patients with HABP\/VABP.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01313-25","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:00:36Z","timestamp":1769432436000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Imipenem\/cilastatin\/relebactam dosing regimen justification using exposure\u2013efficacy analyses in participants with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia in the RESTORE-IMI 2 phase 3 study"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-0899","authenticated-orcid":true,"given":"Munjal","family":"Patel","sequence":"first","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett","family":"Nieddu","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5942-9707","authenticated-orcid":true,"given":"C. Andrew","family":"DeRyke","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Young","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke Francis","family":"Chen","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Paschke","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5009-2139","authenticated-orcid":false,"given":"Matthew L.","family":"Rizk","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdous","family":"Gheyas","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc.","place":["Rahway, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12206526"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02135-z"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-0926-5"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30403-7"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0596-8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-03091-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky107"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2019.10.028"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piaa056"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01471-8"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa803"},{"key":"e_1_3_4_13_2","unstructured":"European Medicines Agency. 2020. Recarbrio 500 mg\/500 mg\/250 mg powder for solution for infusion: summary of product characteristics. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/recarbrio-epar-product-information_en.pdf"},{"key":"e_1_3_4_14_2","unstructured":"RECARBRIO (imipenem\/cilastatin\/relebactam). Prescribing Information. 2022. Rahway NJ USA Merck Sharp & Dohme LLC. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/212819s002lbl.pdf."},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz530"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2010.0639"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12030475"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70036-2"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000259585"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181961bff"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2009.06.008"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13158"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00280-18"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12462"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlad011"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01399-21"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12585"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01313-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01313-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:00:47Z","timestamp":1772632847000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01313-25"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,4]]}},"alternative-id":["10.1128\/aac.01313-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01313-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"2025-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01313-25"}}