{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:08:12Z","timestamp":1786464492105,"version":"build-2736575974"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007605","name":"Aarhus Universitet","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Spine J"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spondylodiscitis is a severe infection associated with considerable morbidity and mortality. The prevalence of gram-negative infections is on the rise, posing significant therapeutic challenges. Cefepime\/enmetazobactam constitutes a novel antibiotic combination that offers broad-spectrum activity against resistant gram-negative organisms. However, its pharmacokinetic profile within spinal tissues remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To dynamically assess unbound steady-state concentrations of cefepime\/enmetazobactam in healthy vertebral cancellous bone, intervertebral disc, and paravertebral muscle after both short-term and continuous infusions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>16 pigs were randomised to receive either short-term infusion (3 doses of 2\u00a0g\/0.5\u00a0g cefepime\/enmetazobactam administered over 2\u00a0h, repeated every 8\u00a0h) or continuous infusion (1\u00a0g\/0.25\u00a0g loading dose administered over 15\u00a0min, followed by 6\u00a0g\/1.5\u00a0g administered over 15\u00a0h and 45\u00a0min). Steady state was assumed during the third dosing interval (16\u201324\u00a0h). Microdialysis was employed to sample interstitial fluid from spondylodiscitis-relevant tissues: vertebral cancellous bone, intervertebral disc and paravertebral muscle, at steady state for 8\u00a0h. The unbound concentrations of cefepime and enmetazobactam were quantified by LC\u2013MS\/MS. The primary endpoint was to determine the time above relevant MIC (T\u2009&gt;\u2009MIC) for cefepime (0.125, 4, 8, and 32 mg\/L) and the time above relevant concentration threshold (T\u2009&gt;\u2009Ct) for enmetazobactam (2 and 8 mg\/L).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For both cefepime and enmetazobactam, there were no differences in T\u2009&gt;\u2009MIC and T\u2009&gt;\u2009Ct when comparing dosing regimens, applying the conventional targets of MIC 0.125, 4, and 8 mg\/L, and Ct of 2 mg\/L. Only when applying the aggressive targets of MIC 32 mg\/L and Ct 8 mg\/L did continuous infusion yield longer T\u2009&gt;\u2009MIC and T\u2009&gt;\u2009Ct compared with short-term infusion in both the vertebral cancellous bone and intervertebral disc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both cefepime and enmetazobactam consistently reached theoretically effective unbound steady-state tissue levels in relevant target tissues for spondylodiscitis, irrespective of the dosing regimen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00586-026-10011-5","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T11:06:26Z","timestamp":1779275186000},"page":"4950-4958","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cefepime\/enmetazobactam steady-state concentrations in spondylodiscitis-relevant tissues: an experimental porcine study"],"prefix":"10.1007","volume":"35","author":[{"given":"Maria Bech Damsgaard","family":"Nielsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads Kristian Duborg","family":"Mikkelsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kresten Wendell","family":"Rickers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Crocoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Poborsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nis Pedersen","family":"J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Soriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiken","family":"Stilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Bue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"10011_CR1","doi-asserted-by":"crossref","unstructured":"Baryeh K, Anazor F, Iyer S, Rajagopal T (2022) Spondylodiscitis in adults: diagnosis and management. 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