{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:29:25Z","timestamp":1792114165796,"version":"4.4.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1R21\/R33 AI121689-01"],"award-info":[{"award-number":["1R21\/R33 AI121689-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Carbapenemase-producing\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (KPC) are globally emerging pathogens that cause life-threatening infections. Novel treatment alternatives are urgently needed. We therefore investigated the effectiveness of three novel bacteriophages (Spivey, Pharr, and Soft) in a neutropenic murine model of KPC gastrointestinal colonization, translocation, and disseminated infection. Bacteriophage efficacy was determined by residual bacterial burden of KPC (CFU\/g) in kidneys. Parallel studies were conducted of bacteriophage pharmacokinetics and resistance. Treatment of mice with 5 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      PFU of phage cocktail via intraperitoneal injection was effective in significantly reducing renal KPC CFU by 100-fold (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01) when administered every 24 h and 1000-fold (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01) every 12 h. Moreover, a combination of bacteriophage and ceftazidime-avibactam produced a synergistic effect, resulting in a 10\n                      <jats:sup>5<\/jats:sup>\n                      -fold reduction in bacterial burden in cecum and kidney (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001 in both tissues). Prophylactic administration of bacteriophages via oral gavage did not prevent KPC translocation to the kidneys. Bacteriophage decay determined by linear regression of the ln of mean concentrations demonstrated R\n                      <jats:sup>2<\/jats:sup>\n                      values in plasma of 0.941, kidney 0.976, and cecum 0.918, with half-lives of t\n                      <jats:sub>1\/2<\/jats:sub>\n                      = 2.5 h. Furthermore, a phage-resistant mutant displayed increased sensitivity to serum killing\n                      <jats:italic>in vitro<\/jats:italic>\n                      , but did not show significant defects in renal infection\n                      <jats:italic>in vivo<\/jats:italic>\n                      . A combination of bacteriophages demonstrated significant efficacy alone and synergy with ceftazidime\/avibactam in the treatment of experimental disseminated KPC infection in neutropenic mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00919-24","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T09:00:16Z","timestamp":1734685216000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Bacteriophage treatment is effective against carbapenem-resistant\n                    <i>Klebsiella pneumoniae<\/i>\n                    (KPC) in a neutropenic murine model of gastrointestinal translocation and renal infection"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-957X","authenticated-orcid":true,"given":"Panagiotis","family":"Zagaliotis","sequence":"first","affiliation":[{"name":"Transplantation\/Oncology Program, Division of Infectious Diseases, Weill Cornell Medicine","place":["New York, USA"]},{"name":"Department of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordyn","family":"Michalik-Provasek","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University","place":["College Station, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Mavridou","sequence":"additional","affiliation":[{"name":"Transplantation\/Oncology Program, Division of Infectious Diseases, Weill Cornell Medicine","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Naing","sequence":"additional","affiliation":[{"name":"Transplantation\/Oncology Program, Division of Infectious Diseases, Weill Cornell Medicine","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis S.","family":"Vizirianakis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]},{"name":"Department of Health Sciences, School of Life and Health Sciences, University of Nicosia","place":["Nicosia, Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Chatzidimitriou","sequence":"additional","affiliation":[{"name":"Deparment of Microbiology, School of Medicine, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9494-6053","authenticated-orcid":true,"given":"Jason J.","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Texas A&M University Department of Animal Science","place":["College Station, USA"]},{"name":"Center for Phage Technology, Texas A&M University","place":["College Station, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-9778","authenticated-orcid":true,"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Transplantation\/Oncology Program, Division of Infectious Diseases, Weill Cornell Medicine","place":["New York, USA"]},{"name":"Center for Innovative Therapeutics and Diagnostics","place":["Richmond, 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