{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:29:10Z","timestamp":1785461350752,"version":"3.56.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100020265","name":"Stan Perron Charitable Foundation","doi-asserted-by":"publisher","award":["000990"],"award-info":[{"award-number":["000990"]}],"id":[{"id":"10.13039\/501100020265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian National Health and Medical Research Council for a Centre of Research Excellence","award":["APP2007007"],"award-info":[{"award-number":["APP2007007"]}]},{"name":"Australian National Health and Medical Research Council for a Centre of Research Excellence","award":["APP2009736"],"award-info":[{"award-number":["APP2009736"]}]},{"name":"Medical Research Future Fund Investigator","award":["APP1197177"],"award-info":[{"award-number":["APP1197177"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Subcutaneous delivery of antibiotics is a practical alternative to IV administration. Meropenem is commonly used to treat infections caused by resistant Gram-negative organisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a prospective, crossover self-controlled study in 11 stable inpatients established on meropenem. Participants received a single dose of subcutaneous meropenem, in 50\u2005mL normal saline via gravity feed. Venous blood sampling was performed at baseline, 0.5, 1, 2, 4 and 8\u2005h following the subcutaneous and IV doses. Antibiotic concentrations were measured using UPLC-MS\/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema\/erythema) were assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Subcutaneous meropenem was well tolerated. The bioavailability of subcutaneous administration was 81.5% (95% CI 71.6%\u201393.2%). Increasing BMI was associated with slower absorption from subcutaneous tissue. Compared with IV, subcutaneous administration resulted in lower peak and higher trough concentrations. Despite the lower bioavailability observed, the PTA for free drug concentrations greater than the MIC for more than 40% of the time between doses was higher for subcutaneous than IV administration at MIC values between 0.03 and 8\u2005mg\/L. Simulated subcutaneous doses of 1.5\u2005g twice daily, or 3\u2005g continuous 24\u2005h infusion had improved PTA relative to standard IV dosing of 1\u2005g three times daily.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Subcutaneous meropenem appears to be well tolerated and has a favourable pharmacokinetic profile. Either 1.5\u2005g twice daily or 3\u2005g as a 24\u2005h subcutaneous infusion could be considered for future evaluation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae398","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T15:19:36Z","timestamp":1731338376000},"page":"209-215","source":"Crossref","is-referenced-by-count":11,"title":["Safety, tolerability and pharmacokinetics of subcutaneous meropenem as an alternative to intravenous administration"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1653-1351","authenticated-orcid":false,"given":"Fionnuala","family":"Murray","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group , Murdoch, Western Australia , , 6150","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okhee","family":"Yoo","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, Western Australia , , 6009","place":["Australia"]},{"name":"Pharmacy, School of Allied Health, The University of Western Australia , Perth, Western Australia , , 6009","place":["Australia"]},{"name":"Institute for Paediatric Perioperative Excellence, The University of Western Australia , Perth, Western Australia , , 6009","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Brophy-Williams","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group , Murdoch, Western Australia , , 6150","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-1084","authenticated-orcid":false,"given":"Matthew","family":"Rawlins","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fiona Stanley Fremantle Hospitals Group , Murdoch, Western Australia , , 6150","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9854","authenticated-orcid":false,"given":"Steven C","family":"Wallis","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A","family":"Roberts","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Herston Infectious Diseases Institute (HeIDI), Metro North Health , Brisbane ,","place":["Australia"]},{"name":"Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women\u2019s Hospital , Brisbane ,","place":["Australia"]},{"name":"Division of Anaesthesiology Critical Care Emergency and Pain Medicine, N\u00eemes University Hospital, University of Montpellier , N\u00eemes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1671-6188","authenticated-orcid":false,"given":"Edward","family":"Raby","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group , Murdoch, Western Australia , , 6150","place":["Australia"]},{"name":"Department of Microbiology, PathWest Laboratory Medicine, Fiona Stanley Hospital , Murdoch, Western Australia , , 6150","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8276-6784","authenticated-orcid":false,"given":"Sam","family":"Salman","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, Western Australia , , 6009","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-5351","authenticated-orcid":false,"given":"Laurens","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group , Murdoch, Western Australia , , 6150","place":["Australia"]},{"name":"Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, Western Australia , , 6009","place":["Australia"]},{"name":"Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Harry Perkins Research Institute, Fiona Stanley Hospital , PO Box 404, Bull Creek 6149, Crawley, Western Australia , , 6009","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"2025010309482881600_dkae398-B1","doi-asserted-by":"publisher","first-page":"e0193436","DOI":"10.1371\/journal.pone.0193436","article-title":"Not \u201cjust\u201d an intravenous line: consumer perspectives on peripheral intravenous cannulation (PIVC). An international cross-sectional survey of 25 countries","volume":"13","author":"Cooke","year":"2018","journal-title":"PLoS One"},{"key":"2025010309482881600_dkae398-B2","article-title":"46th Report, Chapter 2: Prevalence of kidney failure with replacement therapy","author":"Australia and New Zealand Dialysis and Transplant Registry","year":"2023"},{"key":"2025010309482881600_dkae398-B3","first-page":"2640","article-title":"Value of subcutaneous tobramycin","volume":"5","author":"Babinet","year":"1976","journal-title":"Nouv Presse Med"},{"key":"2025010309482881600_dkae398-B4","doi-asserted-by":"publisher","first-page":"370.e1","DOI":"10.1016\/j.cmi.2014.11.017","article-title":"Subcutaneously administered antibiotics: a national survey of current practice from the French Infectious Diseases (SPILF) and Geriatric Medicine (SFGG) society networks","volume":"21","author":"Forestier","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"2025010309482881600_dkae398-B5","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.jamda.2018.03.011","article-title":"Antibiotics by subcutaneous route: a safe and efficient alternative","volume":"19","author":"Noriega","year":"2018","journal-title":"J Am Med Dir Assoc"},{"key":"2025010309482881600_dkae398-B6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.medmal.2019.06.007","article-title":"Subcutaneously administered antibiotics","volume":"50","author":"Colin","year":"2020","journal-title":"Med Mal Infect"},{"key":"2025010309482881600_dkae398-B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jac\/dkac383","article-title":"Subcutaneously administered antibiotics: a review","volume":"78","author":"Jumpertz","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2025010309482881600_dkae398-B8","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1111\/imj.15511","article-title":"Subcutaneous ertapenem delivered by an Australian outpatient parenteral antimicrobial therapy service: a retrospective comparative efficacy study","volume":"51","author":"Hiew","year":"2021","journal-title":"Intern Med J"},{"key":"2025010309482881600_dkae398-B9","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1177\/1098612X15604655","article-title":"Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats","volume":"18","author":"Albarellos","year":"2016","journal-title":"J Feline Med Surg"},{"key":"2025010309482881600_dkae398-B10","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.2460\/ajvr.2002.63.1622","article-title":"Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs","volume":"63","author":"Bidgood","year":"2002","journal-title":"Am J Vet Res"},{"key":"2025010309482881600_dkae398-B11","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1197\/aemj.10.4.390","article-title":"Validation of a verbally administered numerical rating scale of acute pain for use in the emergency department","volume":"10","author":"Bijur","year":"2003","journal-title":"Acad Emerg Med"},{"key":"2025010309482881600_dkae398-B12","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.1093\/jac\/dky314","article-title":"Therapeutic drug monitoring of \u03b2-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures","volume":"73","author":"Wong","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2025010309482881600_dkae398-B13","doi-asserted-by":"publisher","first-page":"7831","DOI":"10.1007\/s00216-019-02184-4","article-title":"A validated LC-MSMS method for the simultaneous quantification of meropenem and vaborbactam in human plasma and renal replacement therapy effluent and its application to a pharmacokinetic study","volume":"411","author":"Parker","year":"2019","journal-title":"Anal Bioanal Chem"},{"key":"2025010309482881600_dkae398-B14","doi-asserted-by":"publisher","first-page":"e50","DOI":"10.1038\/psp.2013.24","article-title":"Modeling and simulation workbench for NONMEM: tutorial on Pirana, PsN, and Xpose","volume":"2","author":"Keizer","year":"2013","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2025010309482881600_dkae398-B15","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.medmal.2014.03.007","article-title":"Subcutaneous and intravenous ceftriaxone administration in patients more than 75 years of age","volume":"44","author":"Gauthier","year":"2014","journal-title":"Med Mal Infect"},{"key":"2025010309482881600_dkae398-B16","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1093\/ageing\/afw143","article-title":"Tolerance of subcutaneously administered antibiotics: a French national prospective study","volume":"46","author":"Roubaud-Baudron","year":"2017","journal-title":"Age Ageing"},{"key":"2025010309482881600_dkae398-B17","first-page":"337","article-title":"Etude pharmaco-clinique comparative de la ceftriaxone par voie sous-cutan\u00e9e et intraveineuse chez la personne \u00e2g\u00e9e","volume":"25","author":"Melin-Coviaux","year":"2000","journal-title":"La Revue de g\u00e9riatrie"},{"key":"2025010309482881600_dkae398-B18","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1159\/000238342","article-title":"Comparative pharmacokinetics of ceftriaxone after subcutaneous and intravenous administration","volume":"31","author":"Borner","year":"1985","journal-title":"Chemotherapy"},{"key":"2025010309482881600_dkae398-B19","doi-asserted-by":"publisher","first-page":"1966.","DOI":"10.1093\/ofid\/ofw172.1514","article-title":"Pharmacokinetic response after subcutaneous administration of ceftriaxone","volume":"3","author":"Muntendam","year":"2016","journal-title":"Open Forum Infect Dis"},{"key":"2025010309482881600_dkae398-B20","doi-asserted-by":"publisher","first-page":"666","DOI":"10.2215\/CJN.13781217","article-title":"Addressing the problem of multidrug-resistant organisms in dialysis","volume":"13","author":"D\u2019Agata","year":"2018","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025010309482881600_dkae398-B21","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1002\/bmc.3622","article-title":"Determination of cefalothin and cefazolin in human plasma, urine and peritoneal dialysate by UHPLC-MS\/MS: application to a pilot pharmacokinetic study in humans","volume":"30","author":"Parker","year":"2016","journal-title":"Biomed Chromatogr"},{"key":"2025010309482881600_dkae398-B22","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1093\/jac\/dkw496","article-title":"Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery","volume":"72","author":"De Cock","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2025010309482881600_dkae398-B23","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/imj.14251","article-title":"Antimicrobial stewardship opportunities among inpatients with diabetic foot infections: microbiology results from a tertiary hospital multidisciplinary unit","volume":"49","author":"Hand","year":"2019","journal-title":"Intern Med J"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/1\/209\/60588403\/dkae398.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/1\/209\/60588403\/dkae398.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T09:49:01Z","timestamp":1735897741000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/80\/1\/209\/7889332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,11,11]]},"published-print":{"date-parts":[[2025,1,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae398","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,11,11]]}}}