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Two highly potent BATSIs being developed are S02030 and MB076 strategically designed to be active against cephalosporinases and carbapenemases, especially KPC. When combined with cefepime, S02030 and MB076 demonstrated potent antimicrobial activity against laboratory and clinical strains of\n              <jats:italic>Enterobacterales<\/jats:italic>\n              expressing a variety of class A and class C \u03b2-lactamases, including\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>KPC-2<\/jats:sub>\n              and\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>KPC-3<\/jats:sub>\n              . Static time-kill assays revealed the bactericidal activity of cefepime in combination with S02030 and MB076 against a multidrug-resistant KPC-producing\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              (KPC-\n              <jats:italic>Kpn<\/jats:italic>\n              -1), in which a \u2265 3-log\n              <jats:sub>10<\/jats:sub>\n              decrease in the bacterial density was observed by 6 h.\n              <jats:italic>In vivo<\/jats:italic>\n              efficacy of MB076 in combination with cefepime was evaluated in a lung infection model where male C57BL\/6 mice were infected intranasally with KPC-\n              <jats:italic>Kpn<\/jats:italic>\n              -1. Cefepime alone administered at 2 h post infection resulted in a 1.07 log\n              <jats:sub>10<\/jats:sub>\n              CFU reduction at 24 h, while cefepime in combination with MB076 resulted in an enhanced reduction of 2.70 log\n              <jats:sub>10<\/jats:sub>\n              CFU (\n              <jats:italic>P<\/jats:italic>\n              &lt; 0.0001) compared to the no treatment control group. In a survival analysis where mice were infected via the tail vein with KPC-\n              <jats:italic>Kpn<\/jats:italic>\n              -1\n              <jats:italic>,<\/jats:italic>\n              all mice treated with placebo or cefepime alone (100 mg\/kg) died, whereas those treated with a 1:4 molar ratio of cefepime-MB076 survived. Our data demonstrate bactericidal activity and\n              <jats:italic>in vivo<\/jats:italic>\n              efficacy of cefepime-MB076 comparable to ceftazidime-avibactam and support the continued development of this combination as a new treatment option for infections caused by class A carbapenemase producing\n              <jats:italic>Enterobacterales,<\/jats:italic>\n              particularly KPC-\n              <jats:italic>Kpn<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00964-24","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T14:01:00Z","timestamp":1738072860000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Restoring cefepime activity against multidrug-resistant KPC-producing\n            <i>Klebsiella pneumoniae<\/i>\n            by combination with boronic acid inhibitors, MB076 and S02030"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-1658","authenticated-orcid":false,"given":"Laura J.","family":"Rojas","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"name":"CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES)","place":["Cleveland, USA"]},{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3366-7912","authenticated-orcid":true,"given":"Travis B.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Keck School of Medicine of the University of Southern California (USC)","place":["Los Angeles, USA"]},{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California (USC)","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Pantapalangkoor","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California (USC)","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena A.","family":"Taracila","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center","place":["Cleveland, USA"]},{"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-216X","authenticated-orcid":false,"given":"Maria L.","family":"Introvigne","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0891-7548","authenticated-orcid":false,"given":"Rajnikant","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina","place":["Chapel Hill, USA"]},{"name":"USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5968-1007","authenticated-orcid":true,"given":"Shekhar","family":"Yeshwante","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1380-9824","authenticated-orcid":true,"given":"Maria F.","family":"Mojica","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"name":"CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES)","place":["Cleveland, USA"]},{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-7898","authenticated-orcid":true,"given":"Krisztina M.","family":"Papp-Wallace","sequence":"additional","affiliation":[{"name":"JMI Laboratories\/Element\u2014Iowa City","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Hujer","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center","place":["Cleveland, USA"]},{"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0650-9540","authenticated-orcid":false,"given":"Fabio","family":"Prati","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-9453","authenticated-orcid":false,"given":"Emilia","family":"Caselli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Spellberg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Keck School of Medicine of the University of Southern California (USC)","place":["Los Angeles, USA"]},{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California (USC)","place":["Los Angeles, USA"]},{"name":"Los Angeles County-USC (LAC+USC) Medical Center","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9674-6250","authenticated-orcid":true,"given":"Philip N.","family":"Rather","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine","place":["Atlanta, USA"]},{"name":"Research Service, Atlanta Veterans Affairs Medical Center","place":["Decatur, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-7770","authenticated-orcid":true,"given":"Gauri G.","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina","place":["Chapel Hill, USA"]},{"name":"USC Alfred E. 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