{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:54:16Z","timestamp":1791410056328,"version":"4.3.3"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"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":["R01AI165519"],"award-info":[{"award-number":["R01AI165519"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21AI151363"],"award-info":[{"award-number":["R21AI151363"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI141479"],"award-info":[{"award-number":["R01AI141479"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["T32AR007534"],"award-info":[{"award-number":["T32AR007534"]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["K23AI154546"],"award-info":[{"award-number":["K23AI154546"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["T32AI138954"],"award-info":[{"award-number":["T32AI138954"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,3,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Enterococcus faecium<\/jats:italic>\n              is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical\n              <jats:italic>E. faecium<\/jats:italic>\n              isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant\n              <jats:italic>E. faecium<\/jats:italic>\n              (VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent\n              <jats:italic>E. faecium<\/jats:italic>\n              bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related\n              <jats:italic>E. faecium<\/jats:italic>\n              strains for at least 2 years and that invasive isolates likely emerged from a large\n              <jats:italic>E. faecium<\/jats:italic>\n              population in the patient\u2019s gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient\u2019s antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and\n              <jats:italic>E. faecium. In vitro<\/jats:italic>\n              analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual\n              <jats:italic>E. faecium<\/jats:italic>\n              BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent\n              <jats:italic>E. faecium<\/jats:italic>\n              infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced\n              <jats:italic>E. faecium<\/jats:italic>\n              and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03396-23","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T14:00:44Z","timestamp":1707919244000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["Bacteriophage and antibiotic combination therapy for recurrent\n            <i>Enterococcus faecium<\/i>\n            bacteremia"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-5190","authenticated-orcid":false,"given":"Madison E.","family":"Stellfox","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-5665","authenticated-orcid":true,"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-8211","authenticated-orcid":true,"given":"Ghady","family":"Haidar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailey","family":"Hughes Kramer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Dembinski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihnea R.","family":"Mangalea","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Arya","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Canfield","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4030-9822","authenticated-orcid":true,"given":"Breck A.","family":"Duerkop","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-0103","authenticated-orcid":true,"given":"Daria","family":"Van Tyne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091213-113003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:82532"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy947"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/tid.14041"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13091785"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad335"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00143-21"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.23777"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.26717\/BJSTR.2019.18.003195"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00993-20"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01623-21"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11030392"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11091175"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00340-23"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01403-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.024"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03396-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03396-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T18:15:57Z","timestamp":1723400157000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03396-23"}},"subtitle":[],"editor":[{"given":"Bruce 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