{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:55:01Z","timestamp":1774439701422,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Eumedica SA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Bone and joint infections (BJIs) due to third-generation cephalosporin-resistant (3GC-R) Enterobacterales are particularly challenging-to-treat infections, and their treatment often relies on carbapenems. Due to its stability towards various beta-lactamases, as well as its limited spectrum of activity, temocillin could be a promising alternative. This study evaluated the in vitro activity of temocillin against a collection of 3GC-R Enterobacterales isolates from BJIs and modelled the probability of PK\/PD target attainment according to the dosage regimen used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MICs of temocillin and seven comparators (ertapenem, imipenem, meropenem, levofloxacin, delafloxacin, doxycycline and tigecycline) were determined using gradient strips for 104 3GC-R Enterobacterales isolates from BJIs in three French hospitals. Isolates were characterized about their mechanism of resistance to 3GC (ESBL or hyperproduced cephalosporinase). PK\/PD simulations were performed with six dosage regimens and different stages of renal function in order to calculate PTA according to temocillin MIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Temocillin showed a susceptibility rate of 92.3% (96\/104) in 3GC-R isolates from BJIs: 95.3% (61\/64) in ESBL producers and 87.5% (35\/40) in AmpC hyperproducers. Temocillin was the only alternative to carbapenems for 25% (26\/104) of isolates. PTA values increased with declining renal function. In normorenal patients, none of the tested regimen achieved adequate PTA up to the Enterobacterales breakpoint (16\u2005mg\/L).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated the high in vitro efficacy of temocillin against 3GC-R Enterobacterales from BJIs, regardless of the underlying resistance mechanism. However, dosage adjustments based on the strain\u2019s MIC and the patient's renal function are crucial for optimal efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag105","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T08:35:03Z","timestamp":1774427703000},"source":"Crossref","is-referenced-by-count":0,"title":["Temocillin: a therapeutic alternative in bone and joint infections due to third generation cephalosporin-resistant Enterobacterales?"],"prefix":"10.1093","volume":"81","author":[{"given":"Louise","family":"Piquart","sequence":"first","affiliation":[{"name":"Service de Bact\u00e9riologie, Institut des Agents Infectieux, Hospices Civils de Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-2932","authenticated-orcid":false,"given":"Sylvain","family":"Goutelle","sequence":"additional","affiliation":[{"name":"Service de Pharmacie, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon , Lyon ,","place":["France"]},{"name":"Laboratoire de Biom\u00e9trie et Biologie Evolutive, UMR CNRS 5558, Universit\u00e9 Claude Bernard Lyon 1, Univ Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Maillard","sequence":"additional","affiliation":[{"name":"Service de Bact\u00e9riologie, Institut des Agents Infectieux, Hospices Civils de Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Boisset","sequence":"additional","affiliation":[{"name":"Laboratoire de Bact\u00e9riologie, CHU Grenoble , Grenoble ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Carricajo","sequence":"additional","affiliation":[{"name":"Laboratoire de Bact\u00e9riologie, CHU Saint Etienne , Saint-Etienne ,","place":["France"]},{"name":"Centre International de Recherche en Infectiologie (CIRI), INSERM U1111-CNRS UMR5308-Universit\u00e9 Lyon 1-ENS Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9471-2655","authenticated-orcid":false,"given":"Anne","family":"Tristan","sequence":"additional","affiliation":[{"name":"Service de Bact\u00e9riologie, Institut des Agents Infectieux, Hospices Civils de Lyon , Lyon ,","place":["France"]},{"name":"Centre International de Recherche en Infectiologie (CIRI), INSERM U1111-CNRS UMR5308-Universit\u00e9 Lyon 1-ENS Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Ga\u00eblle","family":"Ranc","sequence":"additional","affiliation":[{"name":"Service de Bact\u00e9riologie, Institut des Agents Infectieux, Hospices Civils de Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Laurent","sequence":"additional","affiliation":[{"name":"Service de Bact\u00e9riologie, Institut des Agents Infectieux, Hospices Civils de Lyon , Lyon ,","place":["France"]},{"name":"Centre International de Recherche en Infectiologie (CIRI), INSERM U1111-CNRS UMR5308-Universit\u00e9 Lyon 1-ENS Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7388-4087","authenticated-orcid":false,"given":"C\u00e9line","family":"Dupieux","sequence":"additional","affiliation":[{"name":"Service de Bact\u00e9riologie, Institut des Agents Infectieux, Hospices Civils de Lyon , Lyon ,","place":["France"]},{"name":"Centre International de Recherche en Infectiologie (CIRI), INSERM U1111-CNRS UMR5308-Universit\u00e9 Lyon 1-ENS Lyon , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"2026032504310697200_dkag105-B1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jinf.2020.12.010","article-title":"Epidemiology of complex bone and joint infections in France using a national registry: the CRIOAc network","volume":"82","author":"Lemaignen","year":"2021","journal-title":"J Infect"},{"key":"2026032504310697200_dkag105-B2","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.otsr.2013.02.011","article-title":"Bacterial epidemiology of osteoarticular infections in a referent center: 10-year study","volume":"99","author":"Tit\u00e9cat","year":"2013","journal-title":"Orthop Traumatol Surg Res"},{"key":"2026032504310697200_dkag105-B3","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/microorganisms8020269","article-title":"Gut microbiota, antibiotic therapy and antimicrobial resistance: a narrative review","volume":"8","author":"Pilmis","year":"2020","journal-title":"Microorganisms"},{"key":"2026032504310697200_dkag105-B4","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.ijantimicag.2018.08.026","article-title":"Carbapenems and alternative \u03b2-lactams for the treatment of infections due to extended-spectrum \u03b2-lactamase-producing Enterobacteriaceae: what impact on intestinal colonisation resistance?","volume":"52","author":"Woerther","year":"2018","journal-title":"Int J Antimicrob Agents"},{"key":"2026032504310697200_dkag105-B5","doi-asserted-by":"publisher","first-page":"649.e1","DOI":"10.1016\/j.cmi.2015.03.013","article-title":"Elaboration of a consensual definition of de-escalation allowing a ranking of \u03b2-lactams","volume":"21","author":"Weiss","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"2026032504310697200_dkag105-B6","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1086\/677633","article-title":"Development of an antibiotic spectrum score based on veterans affairs culture and susceptibility data for the purpose of measuring antibiotic de-escalation: a modified Delphi approach","volume":"35","author":"Madaras-Kelly","year":"2014","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2026032504310697200_dkag105-B7","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1080\/21505594.2016.1222343","article-title":"The global epidemiology of carbapenemase-producing Enterobacteriaceae","volume":"8","author":"van Duin","year":"2017","journal-title":"Virulence"},{"key":"2026032504310697200_dkag105-B8","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1093\/jac\/dkn511","article-title":"Temocillin revived","volume":"63","author":"Livermore","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B9","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3390\/antibiotics11040493","article-title":"Temocillin: applications in antimicrobial stewardship as a potential carbapenem-sparing antibiotic","volume":"11","author":"Lupia","year":"2022","journal-title":"Antibiotics"},{"key":"2026032504310697200_dkag105-B10","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1097\/FTD.0b013e31825c4ba6","article-title":"Accurate detection of outliers and subpopulations with Pmetrics, a nonparametric and parametric pharmacometric modeling and simulation package for R","volume":"34","author":"Neely","year":"2012","journal-title":"Ther Drug Monit"},{"key":"2026032504310697200_dkag105-B11","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1093\/jac\/dkae215","article-title":"Pharmacokinetics and pharmacological target attainment of standard temocillin dosing in non-critically ill patients with complicated urinary tract infections","volume":"79","author":"Wijnant","year":"2024","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B12","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1093\/jac\/dkm467","article-title":"Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection","volume":"61","author":"De Jongh","year":"2008","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B13","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1093\/jac\/dku465","article-title":"Temocillin (6g daily) in critically ill patients: continuous infusion versus three times daily administration","volume":"70","author":"Laterre","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B14","doi-asserted-by":"publisher","first-page":"e0205221","DOI":"10.1128\/aac.02052-21","article-title":"Modelled target attainment after temocillin treatment in severe pneumonia: systemic and epithelial lining fluid pharmacokinetics of continuous versus intermittent infusions","volume":"66","author":"Layios","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032504310697200_dkag105-B15","doi-asserted-by":"publisher","first-page":"89","DOI":"10.2165\/00003088-200948020-00002","article-title":"Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamic and bioanalytical considerations","volume":"48","author":"Landersdorfer","year":"2009","journal-title":"Clin Pharmacokinet"},{"key":"2026032504310697200_dkag105-B16","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1093\/jac\/dkr317","article-title":"Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and\/or derepressed AmpC \u03b2-lactamase-producing Enterobacteriaceae","volume":"66","author":"Balakrishnan","year":"2011","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B17","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1093\/jac\/dkaa486","article-title":"Efficacy of temocillin against MDR Enterobacterales: a retrospective cohort study","volume":"76","author":"Alexandre","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B18","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1007\/s10096-017-3091-8","article-title":"Activity of temocillin and 15 other agents, including fosfomycin and colistin, against Enterobacteriaceae in Hong Kong","volume":"36","author":"Ip","year":"2017","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2026032504310697200_dkag105-B19","doi-asserted-by":"publisher","first-page":"Doc08","DOI":"10.3205\/id000077","article-title":"Comparative in vitro activity of piperacillin-tazobactam and temocillin against third-generation cephalosporin-resistant, carbapenem-susceptible Escherichia coli and Klebsiella pneumoniae","volume":"9","author":"Kresken","year":"2021","journal-title":"GMS Infect Dis"},{"key":"2026032504310697200_dkag105-B20","doi-asserted-by":"publisher","first-page":"115368","DOI":"10.1016\/j.diagmicrobio.2021.115368","article-title":"Temocillin susceptibility among Enterobacterales strains recovered from blood culture in France","volume":"100","author":"Farfour","year":"2021","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2026032504310697200_dkag105-B21","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1093\/jac\/36.3.483","article-title":"The ability of beta-lactam antibiotics to select mutants with derepressed beta-lactamase synthesis from Citrobacter freundii","volume":"36","author":"Stapleton","year":"1995","journal-title":"J Antimicrob Chemother"},{"key":"2026032504310697200_dkag105-B22","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/S1473-3099(21)00407-2","article-title":"The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota: a randomised multicentre clinical trial in Sweden","volume":"22","author":"Edlund","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"Suppl 5","key":"2026032504310697200_dkag105-B23","doi-asserted-by":"publisher","first-page":"43","DOI":"10.2165\/00003495-198500295-00010","article-title":"Influence of temocillin on human bowel flora","volume":"29","author":"Mittermayer","year":"1985","journal-title":"Drugs"},{"key":"2026032504310697200_dkag105-B24","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1007\/s10096-015-2406-x","article-title":"Amoxicillin plus temocillin as an alternative empiric therapy for the treatment of severe hospital-acquired pneumonia: results from a retrospective audit","volume":"34","author":"Habayeb","year":"2015","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2026032504310697200_dkag105-B25","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s40262-017-0584-7","article-title":"Pharmacokinetics and pharmacodynamics of temocillin","volume":"57","author":"Alexandre","year":"2018","journal-title":"Clin Pharmacokinet"},{"key":"2026032504310697200_dkag105-B26","doi-asserted-by":"publisher","first-page":"dlac132","DOI":"10.1093\/jacamr\/dlac132","article-title":"Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study","volume":"5","author":"Dinh","year":"2022","journal-title":"JAC Antimicrob Resist"},{"key":"2026032504310697200_dkag105-B27","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jinf.2008.08.001","article-title":"Spinal infection caused by ESBL-producing Klebsiella pneumoniae treated with temocillin","volume":"57","author":"Barton","year":"2008","journal-title":"J Infect"},{"key":"2026032504310697200_dkag105-B28","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1093\/jpids\/pis110","article-title":"Successful use of temocillin as salvage therapy for cervical osteomyelitis secondary to multidrug-resistant Burkholderia cepacia","volume":"3","author":"Rodriguez","year":"2014","journal-title":"J Pediatr Infect Dis Soc"},{"key":"2026032504310697200_dkag105-B29","doi-asserted-by":"publisher","first-page":"dlae164","DOI":"10.1093\/jacamr\/dlae164","article-title":"Effectiveness of temocillin in treatment of non-urinary tract infections caused by ESBL-producing Enterobacterales and risk factors for failure","volume":"6","author":"Mamona Kilu","year":"2024","journal-title":"JAC Antimicrob Resist"},{"key":"2026032504310697200_dkag105-B30","doi-asserted-by":"publisher","first-page":"dlae171","DOI":"10.1093\/jacamr\/dlae171","article-title":"Real-life use of temocillin in the treatment of bone and joint infections due to extended spectrum \u03b2-lactamase-producing Enterobacterales","volume":"6","author":"Lahouati","year":"2024","journal-title":"JAC Antimicrob Resist"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/4\/dkag105\/67507161\/dkag105.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/4\/dkag105\/67507161\/dkag105.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T08:35:05Z","timestamp":1774427705000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag105\/8540106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag105","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,4]]},"article-number":"dkag105"}}