{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:09:31Z","timestamp":1781269771585,"version":"3.54.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PAIDI","award":["P20-00985"],"award-info":[{"award-number":["P20-00985"]}]},{"name":"Modalidad contrato postdoctoral especialista\u2019 from the Consejer\u00eda de Salud y Familias, Junta de Andaluc\u00eda","award":["RH-0136-2020"],"award-info":[{"award-number":["RH-0136-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at \u226416\u2005mg\/L (susceptible with increased exposure) based on a dose of 2\u2005g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time\u2013kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MIC\u200a\u2264\u200a16\u2005mg\/L) and three as resistant (MIC\u200a&amp;gt;\u200a16\u2005mg\/L). The HFIM was performed over 3\u2005days to mimic human-like pharmacokinetics of 2\u2005g q8h. Bacterial counts were performed by plating on Mueller\u2013Hinton agar (MHA) and MHA containing 64\u2005mg\/L temocillin to detect resistant subpopulations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All isolates showed a reduction in bacterial population of at least 3\u2005log cfu\/mL within the first 8\u2005h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30\u2005min may be inadequate to prevent the emergence of resistant variants.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae027","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T14:24:18Z","timestamp":1707488658000},"page":"784-789","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of temocillin efficacy against KPC-2-producing <i>Klebsiella pneumoniae<\/i> isolates in a hollow-fibre infection model"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3603-6800","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Rodr\u00edguez-Ochoa","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3775-5330","authenticated-orcid":false,"given":"Patricia","family":"P\u00e9rez-Palacios","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena , Sevilla , Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Merino-Boh\u00f3rquez","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n de Farmacia Hospitalaria, Hospital Universitario Virgen Macarena , Sevilla , Spain"},{"name":"Departamento de Farmacolog\u00eda, Facultad de Farmacia, Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-6553","authenticated-orcid":false,"given":"Miriam","family":"Ortiz-Padilla","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena , Sevilla , Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Vel\u00e1zquez-Escudero","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-9001","authenticated-orcid":false,"given":"Jes\u00fas","family":"Rodr\u00edguez-Ba\u00f1o","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena , Sevilla , Spain"},{"name":"Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla , Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2228-2294","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Rodr\u00edguez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid , Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla , Avda. S\u00e1nchez Pizju\u00e1n s\/n., 41009 Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-5891","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Pascual","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Hospital Universitario Virgen Macarena , Sevilla , Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid , Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla , Avda. S\u00e1nchez Pizju\u00e1n s\/n., 41009 Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-6764","authenticated-orcid":false,"given":"Fernando","family":"Docobo-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Universidad de Sevilla , Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid , Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla , Avda. S\u00e1nchez Pizju\u00e1n s\/n., 41009 Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"2024040202341095800_dkae027-B1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.mib.2006.08.011","article-title":"The CTX-M \u03b2-lactamase pandemic","volume":"9","author":"Cant\u00f3n","year":"2006","journal-title":"Curr Opin Microbiol"},{"key":"2024040202341095800_dkae027-B2","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1093\/cid\/ciaa1478","article-title":"Infectious Diseases Society of America guidance on the treatment of extended-spectrum \u03b2-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa)","volume":"72","author":"Tamma","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024040202341095800_dkae027-B3","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1093\/jac\/dkx181","article-title":"Sparing carbapenem usage","volume":"72","author":"Wilson","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2024040202341095800_dkae027-B4","author":"WHO"},{"key":"2024040202341095800_dkae027-B5","doi-asserted-by":"crossref","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":"2024040202341095800_dkae027-B6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1128\/AAC.26.3.335","article-title":"Affinity of temocillin for Escherichia coli K-12 penicillin-binding proteins","volume":"26","author":"Labia","year":"1984","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202341095800_dkae027-B7","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1128\/AAC.31.8.1271","article-title":"Improved sensitivity in assays for binding of novel \u03b2-lactam antibiotics to penicillin-binding proteins of Escherichia coli","volume":"31","author":"Bush","year":"1987","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202341095800_dkae027-B8","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/jac\/dkr543","article-title":"Role of MexAB-OprM in intrinsic resistance of Pseudomonas aeruginosa to temocillin and impact on the susceptibility of strains isolated from patients suffering from cystic fibrosis","volume":"67","author":"Buyck","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2024040202341095800_dkae027-B9","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1128\/AAC.22.3.453","article-title":"Antibacterial activity and \u03b2-lactamase stability of temocillin","volume":"22","author":"Jules","year":"1982","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202341095800_dkae027-B10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/jac\/dkn511","article-title":"Temocillin revived","volume":"63","author":"Livermore","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"2024040202341095800_dkae027-B11","author":"EUCAST"},{"key":"2024040202341095800_dkae027-B12","doi-asserted-by":"crossref","first-page":"e0143322","DOI":"10.1128\/aac.01433-22","article-title":"Pharmacodynamics of temocillin in neutropenic murine infection models","volume":"67","author":"Muller","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202341095800_dkae027-B13","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1093\/jac\/dkw066","article-title":"Activity of temocillin in a lethal murine model of infection of intra-abdominal origin due to KPC-producing Escherichia coli","volume":"71","author":"Alexandre","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2024040202341095800_dkae027-B14","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1128\/JCM.06094-11","article-title":"Multilocus sequence typing of total-genome-sequenced bacteria","volume":"50","author":"Larsen","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2024040202341095800_dkae027-B15","article-title":".","author":"CLSI","year":"1999.","journal-title":"Methods for determining bactericidal activity of antimicrobial agents: M26-A"},{"key":"2024040202341095800_dkae027-B16","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/jac\/dku465","article-title":"Temocillin (6","volume":"70","author":"Laterre","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2024040202341095800_dkae027-B17","author":"D\u2019Argenio"},{"key":"2024040202341095800_dkae027-B18","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jpba.2013.12.002","article-title":"Development and validation of a high performance liquid chromatography assay for the determination of temocillin in serum of haemodialysis patients","volume":"90","author":"Miranda Bastos","year":"2014","journal-title":"J Pharm Biomed Anal"},{"key":"2024040202341095800_dkae027-B19","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1128\/AAC.00290-09","article-title":"Activity of temocillin against KPC-producing Klebsiella pneumoniae and Escherichia coli","volume":"53","author":"Adams-Haduch","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202341095800_dkae027-B20","doi-asserted-by":"crossref","first-page":"e0035823","DOI":"10.1128\/aac.00358-23","article-title":"Temocillin resistance in the Enterobacter cloacae complex is conferred by a single point mutation in BaeS, leading to overexpression of the AcrD efflux pump","volume":"67","author":"Gu\u00e9rin","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202341095800_dkae027-B21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/10409238.2013.869543","article-title":"Persisters and beyond: mechanisms of phenotypic drug resistance and drug tolerance in bacteria","volume":"49","author":"Kester","year":"2014","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"2024040202341095800_dkae027-B22","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nrmicro.2016.34","article-title":"Distinguishing between resistance, tolerance and persistence to antibiotic treatment","volume":"14","author":"Brauner","year":"2016","journal-title":"Nat Rev Microbiol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/4\/784\/57130772\/dkae027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/4\/784\/57130772\/dkae027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T02:34:49Z","timestamp":1712025289000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/79\/4\/784\/7604317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,9]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2,9]]},"published-print":{"date-parts":[[2024,4,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae027","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,4]]},"published":{"date-parts":[[2024,2,9]]}}}