{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:05:44Z","timestamp":1760123144992,"version":"3.37.3"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>STM-001, a retargeted glycopeptide, is active against MDR E. coli expressing ESBLs including carbapenemases. Herein, we assessed its capability to combat E. coli complicated urinary tract infections (cUTI) in mice driven by clinically important serine (CTX-M-15) and metallo-\u03b2-lactamases (NDM-1).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Plasma and urine pharmacokinetics following IV administration of STM-001 (1\u201350\u2005mg\/kg) were determined in mice via LC-MS\/MS. The effects on bacterial burden (kidney, bladder and urine) were determined in a 7\u2005day mouse cUTI model whereby STM-001 was administered q12h or q24h at 2\u2013100\u2005mg\/kg\/day from Day 4. Efficacy was assessed by the change in log10 cfu\/g or log10 cfu\/mL from vehicle-treated infected mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>MICs of STM-001 for CTX-M-15 and NDM-1 E. coli were 8 and 16\u2005mg\/L, respectively. Blood pharmacokinetic profile was linear and dose-dependent with low clearance of 9.49\u200a\u00b1\u200a0.31\u2005mL\/min\/kg, V\u200a=\u200a0.63\u200a\u00b1\u200a0.02 L\/kg and t\u00bd\u200a=\u200a1.16\u200a\u00b1\u200a0.03\u2005h. High STM-001 concentrations were recovered in urine 0\u20138\u2005h post-administration, reaching up to 120-fold above its MIC. In cUTI efficacy studies, STM-001 (1\u201350\u2005mg\/kg, q12h) reduced CTX-M-15 burden by log10 4.31 (kidney), 3.95 (bladder) and 4.82 (urine) compared with vehicle-treated animals (P\u200a&amp;lt;\u200a0.0001). STM-001 also reduced NDM-1 burden by log10 3.89 (kidney), 3.76 (bladder) and 3.08 (urine) (P\u200a&amp;lt;\u200a0.0001), with similar inhibitory effects following q24h dosing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>STM-001 was highly effective in reducing E. coli burden in kidney, bladder and urine in mouse cUTI models. The observed efficacy with either dosing regimen indicates potential low humanized doses of 1\u20135\u2005mg\/kg. These data support further development of STM-001 as an innovative, carbapenem-sparing antibiotic to combat human cUTIs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac063","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T20:10:10Z","timestamp":1645215010000},"page":"1706-1709","source":"Crossref","is-referenced-by-count":7,"title":["Vancomycin-arginine (STM-001) abrogates ESBL carrier and carbapenem-resistant <i>Escherichia coli<\/i> burden in a murine complicated urinary tract infection model"],"prefix":"10.1093","volume":"77","author":[{"given":"Lewis F.","family":"Neville","sequence":"first","affiliation":[{"name":"SuperTrans Medical Ltd , Tel Aviv-Jaffa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itamar","family":"Shalit","sequence":"additional","affiliation":[{"name":"SuperTrans Medical Ltd , Tel Aviv-Jaffa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0862-9714","authenticated-orcid":false,"given":"Peter A.","family":"Warn","sequence":"additional","affiliation":[{"name":"Magic Bullet Consulting , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob T.","family":"Rendell","sequence":"additional","affiliation":[{"name":"SuperTrans Medical Ltd , Tel Aviv-Jaffa, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"2022053122483142500_dkac063-B1","doi-asserted-by":"crossref","first-page":"691210","DOI":"10.3389\/fcimb.2021.691210","article-title":"Recurrent urinary tract infection: a mystery in search of better model systems","volume":"11","author":"Murray","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2022053122483142500_dkac063-B2","doi-asserted-by":"crossref","first-page":"ofz446","DOI":"10.1093\/ofid\/ofz446","article-title":"Longitudinal nationwide cohort study to assess incidence, outcomes and costs associated with complicated urinary tract infection","volume":"6","author":"Carreno","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2022053122483142500_dkac063-B3","doi-asserted-by":"crossref","first-page":"e00181-19","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial resistance in ESKAPE pathogens","volume":"33","author":"De Oliveira","year":"2020","journal-title":"Clin Microbiol Rev"},{"key":"2022053122483142500_dkac063-B4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/nrurol.2015.199","article-title":"The emerging threat of multidrug resistant Gram-negative bacteria in urology","volume":"12","author":"Zowawi","year":"2015","journal-title":"Nat Rev Urol"},{"key":"2022053122483142500_dkac063-B5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1756287219832172","article-title":"An introduction to the epidemiology and burden of urinary tract infections","volume":"11","author":"Medina","year":"2019","journal-title":"Ther Adv Urol"},{"key":"2022053122483142500_dkac063-B6","doi-asserted-by":"crossref","first-page":"e0220265","DOI":"10.1371\/journal.pone.0220265","article-title":"The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017","volume":"14","author":"Critchley","year":"2019","journal-title":"PLoS One"},{"key":"2022053122483142500_dkac063-B7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.annemergmed.2020.08.022","article-title":"Emergence of extended-spectrum \u03b2-lactamase urinary tract infections among hospitalized emergency department patients in the United States","volume":"77","author":"Talan","year":"2021","journal-title":"Ann Emerg Med"},{"key":"2022053122483142500_dkac063-B8","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1086\/653932","article-title":"Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistant E. coli infections in the United States","volume":"51","author":"Johnson","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2022053122483142500_dkac063-B9","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1055\/s-0035-1544208","article-title":"Carbapenemase-producing Enterobacteriaceae","volume":"36","author":"Doi","year":"2015","journal-title":"Semin Respir Crit Care Med"},{"key":"2022053122483142500_dkac063-B10","doi-asserted-by":"crossref","first-page":"e02416-20","DOI":"10.1128\/AAC.02416-20","article-title":"In-vivo targeting of Escherichia coli with vancomycin-arginine","volume":"65","author":"Neville","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2022053122483142500_dkac063-B11","doi-asserted-by":"crossref","first-page":"e01439-17","DOI":"10.1128\/AAC.01439-17","article-title":"Activity of meropenem-vaborbactam against carbapenem-resistant Enterobacteriaceae in a murine model of pyelonephritis","volume":"62","author":"Weiss","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"article-title":"Guidance Document: Complicated Urinary Tract Infections: Developing Drugs for Treatment","year":"2018","author":"FDA","key":"2022053122483142500_dkac063-B12"},{"issue":"Suppl 1","key":"2022053122483142500_dkac063-B13","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1086\/491712","article-title":"The pharmacokinetic and pharmacodynamic properties of vancomycin","volume":"42","author":"Rybak","year":"2006","journal-title":"Clin Infect Dis"},{"year":"2005","key":"2022053122483142500_dkac063-B14","article-title":"FDA Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers"},{"key":"2022053122483142500_dkac063-B15","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/00325481.2019.1680052","article-title":"Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents","volume":"132","author":"Bader","year":"2020","journal-title":"Postgrad Med"},{"key":"2022053122483142500_dkac063-B16","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1021\/acschembio.9b00565","article-title":"Vancomycin-arginine conjugate inhibits growth of carbapenem-resistant E. coli and targets cell-wall synthesis","volume":"14","author":"Antonopolis","year":"2019","journal-title":"ACS Chem Biol"},{"key":"2022053122483142500_dkac063-B17","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1093\/jac\/dkz167","article-title":"Twenty-four hour pharmacokinetic relationships for intravenous vancomycin and novel urinary biomarkers of acute kidney injury in a rat model","volume":"74","author":"Avedissian","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2022053122483142500_dkac063-B18","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/jac\/dkab405","article-title":"Clinical exposure\u2013response relationship of cefepime\/taniborbactam against Gram-negative organisms in the murine complicated urinary tract infection model","volume":"77","author":"Lasko","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2022053122483142500_dkac063-B19","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11908-020-0716-3","article-title":"Carbapenem-resistant Enterobacterales: considerations for treatment in the era of new antimicrobials and evolving enzymology","volume":"22","author":"Lasko","year":"2020","journal-title":"Curr Infect Dis Rep"},{"key":"2022053122483142500_dkac063-B20","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.idc.2020.08.002","article-title":"Multidrug-resistant bacteria in the community: an update","volume":"34","author":"van Duin","year":"2020","journal-title":"Infect Dis Clin North Am"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/6\/1706\/43893453\/dkac063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/6\/1706\/43893453\/dkac063.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T22:51:24Z","timestamp":1654037484000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/77\/6\/1706\/6539950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,1]]},"references-count":20,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3,1]]},"published-print":{"date-parts":[[2022,5,29]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkac063","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"type":"print","value":"0305-7453"},{"type":"electronic","value":"1460-2091"}],"subject":[],"published-other":{"date-parts":[[2022,6,1]]},"published":{"date-parts":[[2022,3,1]]}}}