{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T14:42:50Z","timestamp":1782139370694,"version":"3.54.5"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Innoviva Specialty Therapeutics"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Sulbactam-durlobactam is approved for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of\n              <jats:italic>Acinetobacter baumannii-calcoaceticus<\/jats:italic>\n              complex. Patients with serious\n              <jats:italic>Acinetobacter<\/jats:italic>\n              infections may require support with continuous renal replacement therapy (CRRT), which presents challenges for optimal dosing of antibiotics. Sulbactam-durlobactam dosing regimens were derived for this population using an\n              <jats:italic>ex vivo<\/jats:italic>\n              CRRT model and Monte Carlo simulation (MCS). Transmembrane clearance (CL\n              <jats:sub>TM<\/jats:sub>\n              ) was determined in hemofiltration (CVVH) and hemodialysis (CVVHD) modes using the Prismaflex M100 and HF1400 hemofilter sets and with effluent rates of 1, 2, and 3 L\/h. Pre-filter, post-filter blood, and effluent samples were collected over 60 min to calculate sieving (SC) and saturation (SA) coefficients for CVVH and CVVHD, respectively. An established population pharmacokinetic model was integrated with the CL\n              <jats:sub>TM<\/jats:sub>\n              ; then, a 1,000 patient MCS was conducted to determine exposures of potential dosing regimens. Adsorption and degradation in the\n              <jats:italic>ex vivo<\/jats:italic>\n              CRRT model were negligible. The overall mean \u00b1 standard deviation SC\/SA was 1.14 \u00b1 0.12 and 0.93 \u00b1 0.08 for sulbactam and durlobactam, respectively. In multivariable regression analyses, effluent rate was the primary driver of CL\n              <jats:sub>TM<\/jats:sub>\n              for both drugs. For effluent rates &lt;3 L\/h, sulbactam-durlobactam 1 g-1g q8h as 3 h infusion achieved a high probability of pharmacodynamic target attainment while retaining area under the curve exposures consistent with the standard dose in non-CRRT patients. For effluent rates \u22653 to 5 L\/h, the optimal regimen was 1 g-1g q6h 3 h infusion. Sulbactam-durlobactam regimens that provide optimum drug exposures for efficacy and safety were identified for CRRT based on the prescribed effluent rate.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01674-23","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T14:01:15Z","timestamp":1733839275000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["<i>Ex vivo<\/i>\n            assessment of sulbactam-durlobactam clearance during continuous renal replacement therapy to guide dosing recommendations"],"prefix":"10.1128","volume":"69","author":[{"given":"Yasmeen","family":"Abouelhassan","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Shen","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Chen","sequence":"additional","affiliation":[{"name":"Innoviva Specialty Therapeutics Inc","place":["Waltham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Ye","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4148-0165","authenticated-orcid":true,"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital","place":["Hartford, USA"]},{"name":"Division of Infectious Diseases, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-3126","authenticated-orcid":true,"given":"Joseph L.","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"CDC antibiotic resistance threats in the United States. https:\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9030119"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000306"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad094"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04808-14"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad095"},{"key":"e_1_3_3_8_2","unstructured":"XACDURO\u00ae medical information. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/216974Orig1s000Correctedlbl.pdf"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00184-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4103\/0970-9185.98357"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-020-0648-y"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05987-11"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc10257"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01040-y"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e32835685ad"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000455897"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10101184"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01086-y"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01674-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01674-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T14:04:21Z","timestamp":1738332261000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01674-23"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,31]]}},"alternative-id":["10.1128\/aac.01674-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01674-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]},"assertion":[{"value":"2023-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01674-23"}}