{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T20:06:49Z","timestamp":1774728409409,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"ContraFect Corporation and USAMRDC","award":["W81XWH1910139"],"award-info":[{"award-number":["W81XWH1910139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>CF-296 is a lysin in pre-clinical development for the treatment of MSSA and MRSA infections, used in addition to standard-of-care (SOC) antibiotics. We evaluated the efficacy of CF-296 alone and in addition to daptomycin or vancomycin against Staphylococcus aureus in the neutropenic mouse thigh infection model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Eight isolates (one MSSA and seven MRSA) were studied. Mice were administered five CF-296 monotherapy doses ranging from 0.5 to 50\u2009mg\/kg intravenously. To assess adjunctive therapy, mice received sub-therapeutic daptomycin alone, sub-therapeutic vancomycin alone, or the five CF-296 doses in addition to either daptomycin or vancomycin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Relative to starting inoculum (5.80\u2009\u00b1\u20090.31\u2009log10 cfu\/thigh), bacterial density in vehicle controls increased by +2.49\u2009\u00b1\u20090.98 across all eight strains. Relative to 24\u2009h controls, a dose\u2013response in bacterial killing (range \u22120.22\u2009\u00b1\u20090.87 to \u22122.01\u2009\u00b1\u20091.71\u2009log10 cfu\/thigh) was observed with increasing CF-296 monotherapy against the eight isolates. Daptomycin and vancomycin resulted in \u22121.36\u2009\u00b1\u20090.77 and \u22121.37\u2009\u00b1\u20091.01\u2009log10 cfu\/thigh bacteria reduction, respectively, relative to 24\u2009h controls. Escalating CF-296 exposures (0.5\u201350\u2009mg\/kg) in addition to daptomycin resulted in an enhanced dose\u2013response, ranging from bacterial killing of \u22120.69 to \u22122.13\u2009log10 cfu\/thigh, relative to daptomycin alone. Similarly, in addition to vancomycin, escalating CF-296 exposures resulted in bacterial reduction ranging from \u22121.37 to \u22122.29\u2009log10 cfu\/thigh, relative to vancomycin alone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Relative to SOC antibiotics (daptomycin or vancomycin), addition of CF-296 resulted in robust and enhanced antibacterial dose\u2013response, achieving \u22651\u2009log10 cfu\/thigh decrease across most doses, highlighting a potential role for CF-296 adjunctive therapy against MSSA and MRSA isolates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab206","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T11:22:03Z","timestamp":1622719323000},"page":"2622-2628","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy assessment of lysin CF-296 in addition to daptomycin or vancomycin against <i>Staphylococcus aureus<\/i> in the murine thigh infection model"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-0924","authenticated-orcid":false,"given":"Tomefa E","family":"Asempa","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole A","family":"DeRosa","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara","family":"Cassino","sequence":"additional","affiliation":[{"name":"ContraFect Corporation, Yonkers, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Lehoux","sequence":"additional","affiliation":[{"name":"ContraFect Corporation, Yonkers, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4324-573X","authenticated-orcid":false,"given":"Raymond","family":"Schuch","sequence":"additional","affiliation":[{"name":"ContraFect Corporation, Yonkers, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"2021091709030192200_dkab206-B1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1017\/ice.2016.174","article-title":"Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the national healthcare safety network at the 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