{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:35:57Z","timestamp":1788514557232,"version":"build-2803163510"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Sulopenem is an oral and intravenous penem antibiotic in clinical development for treatment of urinary tract and intra-abdominal infections caused by multidrug-resistant pathogens. This study evaluated\n              <jats:italic>in vitro<\/jats:italic>\n              antimicrobial activity of sulopenem by post-antibiotic effect (PAE), sub-inhibitory minimal inhibitory concentration PAE effect (PAE-SME), checkerboard testing, and time-kill testing. Testing sulopenem at 1\u00d7, 5\u00d7, or 10\u00d7 the baseline MIC resulted in a PAE interval of 0.0\u20130.7 hours. When exposed to 0.5\u00d7 the sulopenem MIC following 5\u00d7 MIC, all isolate\/agent combinations had PAE-SME values of &gt;4.8 hours. Checkerboard testing revealed no instances of antagonism between sulopenem and comparator agents\u2014indifference was observed in most sulopenem checkerboard combinations. Sulopenem demonstrated bactericidal activity (\u22653 log\n              <jats:sub>10<\/jats:sub>\n              [99.9%] reduction in viable organism counts) in all time-kill assays following 24 hours of incubation at 8\u00d7 the baseline MIC (6\/6), 5\/6 displaying this activity within 8 hours. The present antimicrobial parameters seen at concentrations surrounding the MIC support optimization of sulopenem dosing and further development. The oral dosing regimen of sulopenem etzadroxil\/probenecid 500 mg\/500 mg administered every 12 hours was recently evaluated in two phase 3 clinical trials where sulopenem demonstrated efficacy against amoxicillin-clavulanate in uncomplicated urinary tract infection (uUTI) and against ciprofloxacin in fluoroquinolone-resistant uUTI.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Sulopenem is an oral and intravenous penem antibiotic in clinical development for treatment of urinary tract and intra-abdominal infections caused by multidrug-resistant pathogens. This study evaluated sulopenem via broth microdilution susceptibility testing, PAE, sub-inhibitory MIC PAE effect, checkerboard testing, and time-kill testing. The results of this study\u2014interpreted along with recent pharmacodynamic\n                <jats:italic>in vitro<\/jats:italic>\n                one-compartment and hollow-fiber infection model work\u2014provide insight into the\n                <jats:italic>in vitro<\/jats:italic>\n                activity of sulopenem.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01898-24","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T14:00:20Z","timestamp":1738764020000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of sulopenem antimicrobial activity using\n            <i>in vitro<\/i>\n            time-kill kinetics, synergy, post-antibiotic effect, and sub-inhibitory MIC effect methods against\n            <i>Escherichia coli<\/i>\n            and\n            <i>Klebsiella pneumoniae<\/i>\n            isolates"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2841-6855","authenticated-orcid":true,"given":"Joshua M.","family":"Maher","sequence":"first","affiliation":[{"name":"Element Iowa City\u2013JMI Laboratories","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9769-9019","authenticated-orcid":false,"given":"Michael D.","family":"Huband","sequence":"additional","affiliation":[{"name":"Element Iowa City\u2013JMI Laboratories","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Lindley","sequence":"additional","affiliation":[{"name":"Element Iowa City\u2013JMI Laboratories","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Rhomberg","sequence":"additional","affiliation":[{"name":"Element Iowa City\u2013JMI Laboratories","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-043X","authenticated-orcid":true,"given":"Steven I.","family":"Aronin","sequence":"additional","affiliation":[{"name":"Iterum Therapeutics","place":["Old Saybrook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailaja","family":"Puttagunta","sequence":"additional","affiliation":[{"name":"Iterum Therapeutics","place":["Old Saybrook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1782","authenticated-orcid":true,"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"name":"Element Iowa City\u2013JMI Laboratories","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01688-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac333"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad099"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.5812\/jjm.10887"},{"key":"e_1_3_3_6_2","volume-title":"Antimicrobial activity of sulopenem tested against Gram-positive and Gram-negative organisms from the United States and Europe (2013-2015)","author":"Puttagunta S","year":"2017","unstructured":"Puttagunta S, Dunne M. 2017. 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