{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:45:52Z","timestamp":1789753552156,"version":"4.0.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"crossref","award":["75F40121C00157"],"award-info":[{"award-number":["75F40121C00157"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2]]},"abstract":"\n Background:<\/jats:title>\n Antimicrobial resistance is a growing health concern worldwide. The objective of this study was to evaluate the effect of beta-lactam infusion on the emergence of bacterial resistance in patients with severe pneumonia in the intensive care unit.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Adult intensive care patients receiving cefepime, meropenem, or piperacillin\u2013tazobactam for severe pneumonia caused by Gram-negative bacteria were randomized to receive beta-lactams as an intermittent (30 minutes) or continuous (24 hours) infusion. Respiratory samples for culture and susceptibility testing, with minimum inhibitory concentrations (MIC), were collected once a week for up to 4 weeks. Beta-lactam plasma concentrations were measured and therapeutic drug monitoring was performed using Bayesian software as the standard of care.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The study was terminated early owing to slow enrollment. Thirty-five patients were enrolled in this study. Cefepime (n = 22) was the most commonly prescribed drug at randomization, followed by piperacillin (n = 8) and meropenem (n = 5). Nineteen patients were randomized into the continuous infusion arm and 16 into the intermittent infusion arm.\n Pseudomonas aeruginosa<\/jats:italic>\n was the most common respiratory isolate (n = 19). Eighteen patients were included in the final analyses. No differences in bacterial resistance were observed between arms (\n P<\/jats:italic>\n = 0.67). No significant differences in superinfection (\n P<\/jats:italic>\n = 1), microbiological cure (\n P<\/jats:italic>\n = 0.85), clinical cure at day 7 (\n P<\/jats:italic>\n = 0.1), clinical cure at end of therapy (\n P<\/jats:italic>\n = 0.56), mortality (\n P<\/jats:italic>\n = 1), intensive care unit length of stay (\n P<\/jats:italic>\n = 0.37), or hospital length of stay (\n P<\/jats:italic>\n = 0.83) were observed. Achieving 100% \u0192T > MIC (\n P<\/jats:italic>\n = 0.04) and \u0192T > 4 \u00d7 MIC (\n P<\/jats:italic>\n = 0.02) increased likelihood of clinical cure at day 7 of therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n No differences in the emergence of bacterial resistance or clinical outcomes were observed between intermittent and continuous infusions. Pharmacokinetic\/pharmacodynamic target attainment may be associated with a clinical cure on day 7.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001144","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T08:03:57Z","timestamp":1701245037000},"page":"95-101","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["A Randomized Clinical Trial of Bayesian-Guided Beta-Lactam Infusion Strategy and Associated Bacterial Resistance and Clinical Outcomes in Patients With Severe Pneumonia"],"prefix":"10.1097","volume":"46","author":[{"given":"Nicole F.","family":"Maranchick","sequence":"first","affiliation":[{"name":"Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, Florida;"},{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Trillo-Alvarez","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, College of Medicine, University of Florida, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidhu","family":"Kariyawasam","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, Florida; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Venugopalan","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida;"},{"name":"Department of Pharmacy, UF Health Shands Hospital, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awewura","family":"Kwara","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, Florida; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Rand","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Florida, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Peloquin","sequence":"additional","affiliation":[{"name":"Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, Florida;"},{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad H.","family":"Alshaer","sequence":"additional","affiliation":[{"name":"Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, Florida;"},{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"R3-20250603","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1038\/nbt1206-1497","article-title":"Antibacterial discovery and development\u2014the failure of success?","volume":"24","author":"Fernandes","year":"2006","journal-title":"Nat Biotechnol."},{"key":"R4-20250603","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1007\/s00134-020-05980-0","article-title":"Ventilator-associated pneumonia in adults: a narrative review","volume":"46","author":"Papazian","year":"2020","journal-title":"Intensive Care Med."},{"key":"R5-20250603","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1128\/AAC.38.3.547","article-title":"Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. 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