{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T15:05:15Z","timestamp":1787929515040,"version":"build-2784847793"},"reference-count":218,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["JR22\/00049"],"award-info":[{"award-number":["JR22\/00049"]}]},{"name":"European Development Regional Fund (\u201cA way to achieve Europe\u201d)","award":["JR22\/00049"],"award-info":[{"award-number":["JR22\/00049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6\u20138 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.<\/jats:p>","DOI":"10.3390\/antibiotics12040704","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T04:09:50Z","timestamp":1680581390000},"page":"704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-944X","authenticated-orcid":false,"given":"Laura","family":"Herrera-Hidalgo","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Farmacia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo, 41013 Seville, Spain"},{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda (UCEIMP) Grupo de Resistencias Bacterianas y Antimicrobianos (CIBERINFEC), Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-2879","authenticated-orcid":false,"given":"Beatriz","family":"Fern\u00e1ndez-Rubio","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Farmacia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Luque-M\u00e1rquez","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda (UCEIMP) Grupo de Resistencias Bacterianas y Antimicrobianos (CIBERINFEC), Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-527X","authenticated-orcid":false,"given":"Luis E.","family":"L\u00f3pez-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas y Microbiolog\u00eda, Grupo de Resistencias Bacterianas y Antimicrobianos (CIBERINFEC), Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen Macarena\/SCIC\/Universidad de Sevilla, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Gil-Navarro","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Farmacia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-4462","authenticated-orcid":false,"given":"Ar\u00edstides","family":"de Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda (UCEIMP) Grupo de Resistencias Bacterianas y Antimicrobianos (CIBERINFEC), Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1001\/archinternmed.2008.603","article-title":"Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: The International Collaboration on Endocarditis-Prospective Cohort Study","volume":"169","author":"Murdoch","year":"2009","journal-title":"Arch. 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