{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T02:06:43Z","timestamp":1774404403623,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Drug databases currently do not provide dosing guidance for sulbactam\u2010durlobactam in continuous renal replacement therapy. Herein, we present the first in\u00a0vivo pharmacokinetic (PK) evaluation of sulbactam\u2010durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with carbapenem\u2010resistant\n                      <jats:italic>Acinetobacter baumannii\u2010calcoaceticus<\/jats:italic>\n                      complex (CRAB) bacteremia and ventilator\u2010associated bacterial pneumonia (VABP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 59\u2010year\u2010old critically ill patient (body mass index 60\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) required CVVH and developed CRAB bacteremia secondary to VABP. Sulbactam\u2010durlobactam 2\u2009g every 4\u2009h infused over 3\u2009h was initiated based on previous ex\u00a0vivo data and the effluent rate of 6\u2009L\/h. The sulbactam\u2010durlobactam minimum inhibitory concentration (MIC) was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed. Steady\u2010state pre\u2010filter blood, post\u2010filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The sulbactam\u2010durlobactam MIC was 4\/4 mcg\/mL (susceptible). WGS revealed penicillin\u2010binding protein (PBP)\u20101b and PBP\u20103 mutations. The selected dose exceeded sulbactam and durlobactam PK\/pharmacodynamic (PD) targets with 100% free time above MIC (\n                      <jats:italic>f<\/jats:italic>\n                      T\u2009&gt;\u2009MIC) and the ratio of area under the unbound concentration\u2010time curve to MIC (\n                      <jats:italic>f<\/jats:italic>\n                      AUC\/MIC)\u2009=\u2009139, respectively. The SC for sulbactam and durlobactam was 0.68 and 0.67, respectively, and protein binding was 54% and 51%, respectively. Sulbactam\u2010durlobactam monotherapy resulted in initial microbiological clearance for CRAB bacteremia but recurred later in hospitalization 11\u2009days after sulbactam\u2010durlobactam treatment. The patient was ultimately transitioned to comfort care.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sulbactam\u2010durlobactam monotherapy dosed at 2\u2009g every 4\u2009h (3\u2010h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4\/4 mcg\/ml. Although sulbactam\u2010durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70027","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:39:27Z","timestamp":1747294767000},"page":"396-402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetic and pharmacodynamic evaluation of sulbactam\u2010durlobactam in a critically ill patient on continuous venovenous hemofiltration infected with carbapenem\u2010resistant\n                    <i>Acinetobacter baumannii\u2010calcoaceticus<\/i>\n                    complex"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7703-096X","authenticated-orcid":false,"given":"Wesley D.","family":"Kufel","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice State University of New York at Binghamton School of Pharmacy and Pharmaceutical Sciences  Binghamton New York USA"},{"name":"Deparment of Pharmacy State University of New York Upstate University Hospital  Syracuse New York USA"},{"name":"Division of Infectious Diseases, Department of Medicine State University of New York Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabil","family":"Zeineddine","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine State University of New York Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6467-1806","authenticated-orcid":false,"given":"Aliaa","family":"Fouad","sequence":"additional","affiliation":[{"name":"Center for Anti\u2010Infective Research and Development Hartford Hospital  Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-0932","authenticated-orcid":false,"given":"Hanna F.","family":"Roenfanz","sequence":"additional","affiliation":[{"name":"Center for Anti\u2010Infective Research and Development Hartford Hospital  Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-5665","authenticated-orcid":false,"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen G.","family":"Kline","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jameson","family":"Warner","sequence":"additional","affiliation":[{"name":"Deparment of Pharmacy State University of New York Upstate University Hospital  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9443-0818","authenticated-orcid":false,"given":"Kathleen","family":"Hanrahan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Arnot Ogden Medical Center  Elmira New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-3126","authenticated-orcid":false,"given":"Joseph L.","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti\u2010Infective Research and Development Hartford Hospital  Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"CDC.Antibiotic resistance threats in the United States 2021\u20132022.2014.https:\/\/www.cdc.gov\/antimicrobial\u2010resistance\/data\u2010research\/threats\/update\u20102022.html"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad100"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad094"},{"key":"e_1_2_13_5_1","unstructured":"Xacduro (sulbactam for injection; durlobactam for injection) copackaged for intranveous use (package insert). Innoviva Specialty Therapeutics.2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/216974Orig1s000Correctedlbl.pdf"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00184-6"},{"issue":"1","key":"e_1_2_13_7_1","first-page":"37","article-title":"Sulbactam: a beta\u2010lactamase inhibitor","volume":"7","author":"Noguchi JK","year":"1988","journal-title":"Clin Pharm"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04808-14"},{"key":"e_1_2_13_9_1","unstructured":"Centers for Disease Control and Prevention.Carbapenem\u2010resistantAcinetobacter baumannii(CRAB): An urgent public health threat in United States healthcare facilities.2021Accessed December 19 2024.https:\/\/arpsp.cdc.gov\/story\/cra\u2010urgent\u2010public\u2010health\u2010threat"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11121793"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00794-19"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01674-23"},{"key":"e_1_2_13_13_1","unstructured":"Clinical Laboratory Standards Institute (CLSI).Performance standards for antimicrobial susceptibility testing. 34th ed. 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