{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:30:23Z","timestamp":1769085023009,"version":"3.49.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N025989\/1"],"award-info":[{"award-number":["MR\/N025989\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Roche Pharma, Eli Lilly and Company Limited, UCB Pharma, Novartis, the University of Liverpool and the University of Manchester"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Neonatal sepsis is a serious and frequently lethal infection, often complicated by antimicrobial resistance (including ESBLs) in low- and middle-income countries (LMICs). Flomoxef is an off-patent oxacephem \u03b2-lactam with stability against non-AmpC ESBLs, with potential for utility in these settings. To date, there has been no published flomoxef neonatal population pharmacokinetic (PopPK) model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To summarize the clinical data available for flomoxef, build a neonatal PopPK model and assess the adequacy of different neonatal flomoxef regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A systematic literature search returned all available clinical or pharmacokinetic data of flomoxef use in neonates. Pharmacokinetic data were used to construct a PopPK model, with progressive incorporation of covariates into the final model. Monte Carlo simulations were performed using this final model to simulate drug exposures of different flomoxef regimens to calculate PTAs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Individual-level clinical and pharmacokinetic data were extracted for 313 and 146 neonates, respectively, with population clinical data extracted for a further 199 neonates. Clinical and microbiological success rates were 89.71% and 82.8%, respectively, with minimal side effects. The final PopPK model incorporated body weight and postnatal age as covariates. PTA analyses predicted that IV regimens of 20 mg\/kg q12h, 20 mg\/kg q6\u20138h and 40 mg\/kg q6\u20138h are adequate for neonates aged 0\u20137, 7\u201314 and 14\u201328 days, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>To the best of our knowledge, this is the first published neonatal PopPK model for flomoxef. Given the high treatment success rates, low toxicity rates and off-patent status, this drug has potential for use in the treatment of neonatal sepsis in ESBL-prevalent LMIC settings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab468","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T20:10:14Z","timestamp":1638475814000},"page":"711-718","source":"Crossref","is-referenced-by-count":19,"title":["Flomoxef for neonates: extending options for treatment of neonatal sepsis caused by ESBL-producing Enterobacterales"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-3413","authenticated-orcid":false,"given":"Christopher A","family":"Darlow","sequence":"first","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool , Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool , Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"2022053123365869300_dkab468-B1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.7164\/antibiotics.38.466","article-title":"Synthesis and antibacterial activity of 6315-S, a new member of the oxacephem antibiotic","volume":"38","author":"Tsuji","year":"1985","journal-title":"J Antibiot (Tokyo)"},{"key":"2022053123365869300_dkab468-B2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF01645536","article-title":"The meaning of the development of flomoxef and clinical experience in Japan","volume":"19","author":"Ito","year":"1991","journal-title":"Infection"},{"key":"2022053123365869300_dkab468-B3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s40272-021-00465-z","article-title":"Potential antibiotics for the treatment of neonatal sepsis caused by multidrug-resistant bacteria","volume":"23","author":"Darlow","year":"2021","journal-title":"Paediatr Drugs"},{"key":"2022053123365869300_dkab468-B4","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/S0140-6736(17)31002-4","article-title":"Neonatal sepsis","volume":"390","author":"Shane","year":"2017","journal-title":"Lancet"},{"key":"2022053123365869300_dkab468-B5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2471\/BLT.14.139790","article-title":"Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013","volume":"93","author":"Oza","year":"2015","journal-title":"Bull World Health Organ"},{"key":"2022053123365869300_dkab468-B6","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1473-3099(14)70804-7","article-title":"Estimates of possible severe bacterial infection in neonates in sub-Saharan Africa, south Asia, and Latin America for 2012: a systematic review and meta-analysis","volume":"14","author":"Seale","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"2022053123365869300_dkab468-B7","author":"Fuchs"},{"key":"2022053123365869300_dkab468-B8","author":"WHO. 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