{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:04:17Z","timestamp":1784009057640,"version":"3.55.0"},"reference-count":109,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR i4i PDA","award":["NIHR205511"],"award-info":[{"award-number":["NIHR205511"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018955","name":"Leeds Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203331"],"award-info":[{"award-number":["NIHR203331"]}],"id":[{"id":"10.13039\/501100018955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Meropenem is a broad-spectrum carbapenem reserved for severe infections. Pharmacokinetic variability has been observed in meropenem patients, and its optimal pharmacological target remains unclear. This meta-analysis evaluated meropenem exposure, target attainment, and their association with clinical outcomes to clarify effective pharmacological targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following PRISMA (PROSPERO CRD42024499652), studies were identified that measured meropenem concentrations in patient samples and reported clinical outcomes. Studies were synthesized and predictors for clinical outcomes were identified by meta-analysis. Patient-level data, provided by authors, were analysed by multivariate logistic regression to identify predictors for clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 42 studies were included, comprising 2264 patients. Most studies had a high risk of bias in this context. Pooled clinical cure was 70.0% and 30-day mortality 22.2%. Meropenem concentration was not associated with clinical cure (OR 1.01 per mg\/L, 95% CI 0.97\u20131.05, P\u200a=\u200a0.702), whereas attaining 100%\u0192T\u200a&amp;gt;\u200aMIC was marginally associated with cure (OR 1.02 per 1%, 1.00\u20131.04, P\u200a=\u200a0.0552). Higher meropenem exposure was associated with increased 30-day mortality (OR 1.064 per mg\/L, 1.008\u20131.124, P\u200a=\u200a0.025). In patient-level analysis (six studies, 295 patients), meropenem exposure, SOFA score and age were each independently associated with mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Higher meropenem concentrations were associated with increased mortality across both cohort and patient-level analyses, challenging the assumption that universally higher dosing benefits all patients. However, residual confounding by illness severity could not be excluded, thus this finding should be considered hypothesis generating. Attaining 100%\u0192T\u200a&amp;gt;\u200aMIC may improve cure while avoiding excessive concentrations may reduce harm, further research into meropenem personalized dosing is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag230","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:19:23Z","timestamp":1784006363000},"source":"Crossref","is-referenced-by-count":0,"title":["Systematic review and meta-analysis to identify meropenem exposures and pharmacological targets predictive of clinical outcomes"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0772-5384","authenticated-orcid":false,"given":"Tim","family":"Luxton","sequence":"first","affiliation":[{"name":"School of Electronics and Electrical Engineering, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"West","sequence":"additional","affiliation":[{"name":"Leeds Institute of Health Sciences, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"King","sequence":"additional","affiliation":[{"name":"Leeds Institute of Health Sciences, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gould","sequence":"additional","affiliation":[{"name":"Leeds Teaching Hospitals Trust Anaesthesia and Intensive Care Medicine, , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"W\u00e4lti","sequence":"additional","affiliation":[{"name":"School of Electronics and Electrical Engineering, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0193-8677","authenticated-orcid":false,"given":"Jonathan A T","family":"Sandoe","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026071401191823900_dkag230-B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"2026071401191823900_dkag230-B2","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11131946","article-title":"Antimicrobial resistance: a growing serious threat for global public health","volume":"11","author":"Salam","year":"2023","journal-title":"Healthcare"},{"key":"2026071401191823900_dkag230-B3","author":"The WHO"},{"key":"2026071401191823900_dkag230-B4","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11030421","article-title":"Mechanisms of action of carbapenem resistance","volume":"11","author":"Aurilio","year":"2022","journal-title":"Antibiotics"},{"key":"2026071401191823900_dkag230-B5","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1093\/cid\/cir202","article-title":"Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention","volume":"53","author":"Gupta","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2026071401191823900_dkag230-B6","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1128\/JCM.00418-06","article-title":"Characterization of a large outbreak by CTX-M-1-producing Klebsiella pneumoniae and mechanisms leading to in vivo carbapenem resistance development","volume":"44","author":"Mena","year":"2006","journal-title":"J Clin Microbiol"},{"key":"2026071401191823900_dkag230-B7","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14040398","article-title":"Prevalence, antimicrobial resistance patterns, and emerging carbapenemase-producing Enterococcus species from different sources in Lagos, Nigeria","volume":"14","author":"Salami","year":"2025","journal-title":"Antibiotics"},{"key":"2026071401191823900_dkag230-B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.111367","article-title":"Carbapenem-resistant Acinetobacter baumannii raises global alarm for new antibiotic regimens","volume":"27","author":"Thacharodi","year":"2024","journal-title":"iScience"},{"key":"2026071401191823900_dkag230-B9","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/2110-5820-2-35","article-title":"Does Beta-lactam pharmacokinetic variability in critically ill patients justify therapeutic drug monitoring? 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