{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:11:11Z","timestamp":1785442271183,"version":"3.56.0"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MOHW | Taiwan Centers for Disease Control","award":["MOHW114-CDC-C-114-114110"],"award-info":[{"award-number":["MOHW114-CDC-C-114-114110"]}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["IV-114-PP-02"],"award-info":[{"award-number":["IV-114-PP-02"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["IV-114-SP-01"],"award-info":[{"award-number":["IV-114-SP-01"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112-2314-B-400-015"],"award-info":[{"award-number":["112-2314-B-400-015"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["113-2314-B-400-011-MY2"],"award-info":[{"award-number":["113-2314-B-400-011-MY2"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      This study aimed to evaluate the concordance of vancomycin susceptibility testing methods, its\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      efficacy, and the mechanisms underlying elevated MICs in\n                      <jats:italic toggle=\"yes\">Elizabethkingia<\/jats:italic>\n                      spp. Vancomycin susceptibilities of 18\n                      <jats:italic toggle=\"yes\">E. anophelis<\/jats:italic>\n                      isolates were determined using multiple assays. The efficacy of vancomycin against five clinical isolates and one laboratory-induced mutant with an elevated vancomycin MIC was evaluated using time-kill assays and\n                      <jats:italic toggle=\"yes\">Galleria mellonella<\/jats:italic>\n                      and murine models. Vancomycin MICs (16\u201332 mg\/L) determined by broth microdilution were consistent with agar dilution, Etest, and MBC assay results. All isolates had zone diameters &lt; 17 mm and were, thus, categorized as non-susceptible according to the CLSI criteria for\n                      <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>\n                      spp. Time-kill assays of five clinical isolates demonstrated that vancomycin at a clinically relevant concentration (4 mg\/L) exhibited poor bactericidal activity similar to that of teicoplanin. Vancomycin improved\n                      <jats:italic toggle=\"yes\">Galleria mellonella<\/jats:italic>\n                      survival in a dose-dependent manner, whereas teicoplanin, dalbavancin, oritavancin, and daptomycin were ineffective. Murine models revealed that vancomycin at a human-equivalent dose (25 mg\/kg twice daily) prolonged survival in most infections and modestly reduced bacterial load, while teicoplanin remained ineffective. Vancomycin efficacy was significantly reduced in\n                      <jats:italic toggle=\"yes\">G. mellonella<\/jats:italic>\n                      and mice infected with a mutant strain exhibiting an elevated MIC (128 mg\/L), which was attributable to spontaneous mutations in\n                      <jats:italic toggle=\"yes\">pbp<\/jats:italic>\n                      4. In conclusion,\n                      <jats:italic toggle=\"yes\">E. anophelis<\/jats:italic>\n                      were consistently non-susceptible to vancomycin as determined by multiple\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      assays. However, vancomycin demonstrated unique\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      activity among glycopeptides although this effect was abrogated by spontaneous mutations leading to elevated MICs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Elizabethkingia anophelis<\/jats:italic>\n                      is a multidrug-resistant pathogen associated with limited treatment options and high mortality. Most commonly considered agents, including fluoroquinolones, piperacillin\/tazobactam, and trimethoprim\/sulfamethoxazole, are increasingly compromised by resistance, toxicity, or inconsistent efficacy. Although vancomycin is not routinely used for Gram-negative infections due to limited outer membrane permeability, case reports have suggested potential benefit in\n                      <jats:italic toggle=\"yes\">Elizabethkingia<\/jats:italic>\n                      infections under critical conditions. In this study, we show that\n                      <jats:italic toggle=\"yes\">E. anophelis<\/jats:italic>\n                      isolates are uniformly non-susceptible to vancomycin\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and exhibit minimal bactericidal activity. However, vancomycin conferred a modest but statistically significant survival benefit in two independent animal models. Importantly, this effect was lost in strains with vancomycin-induced MIC elevation, and genome analysis identified\n                      <jats:italic toggle=\"yes\">pbp4<\/jats:italic>\n                      mutations as a potential underlying mechanism. These findings suggest vancomycin may offer therapeutic benefit when no preferred options are available. They support cautious use in selected cases and highlight the need for continued monitoring of susceptibility and resistance development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02371-25","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T13:01:23Z","timestamp":1759323683000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>In vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    efficacy of vancomycin against\n                    <i>Elizabethkingia<\/i>\n                    species and the impact of increased vancomycin MICs"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-1138","authenticated-orcid":true,"given":"Tzu-Wen","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05031qk94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/05031qk94","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng-Kuang","family":"Yeh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes","place":["Zhunan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Yuan","family":"Hsu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Zhunan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chen","family":"Tan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Zhunan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Cheng","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Zhunan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6940-6450","authenticated-orcid":true,"given":"Shu-Chen","family":"Kuo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Zhunan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Science & Technology, National Yang Ming Chiao Tung University","place":["Hsinchu, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7090295"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02994-15"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60121990"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad322"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.2.192"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.06.021"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa499"},{"key":"e_1_3_4_9_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically\u201311th edition: approved standard M07","author":"Clinical and Laboratory Standards Institute","year":"2018","unstructured":"Clinical and Laboratory Standards Institute. 2018. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically\u201311th edition: approved standard M07. CLSI, Wayne, PA."},{"key":"e_1_3_4_10_2","volume-title":"CLSI document M100Performance standards for antimicrobial susceptibility testing","author":"Clinical and Laboratory Standards Institute","year":"2023","unstructured":"Clinical and Laboratory Standards Institute. 2023. CLSI document M100. Performance standards for antimicrobial susceptibility testing. 33rd ed. 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