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However, there are numerous recently published examples where traditional susceptibility testing methodology fails to accurately predict\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy. We sought to determine if there were efficacious antibiotics against\n                      <jats:italic toggle=\"yes\">S. maltophilia<\/jats:italic>\n                      that have been overlooked due to specious\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      resistance determined by traditional\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      methods. Antibiotic resistance testing was performed utilizing conventional and nutrient-limited media. Antibiotics with discordant minimum inhibitory concentrations (MICs) between the two media were selected for further experimentation. Metal ions were supplemented back into the nutrient-limited media to establish possible mechanisms.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      corroborations of\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      MICs were done utilizing two infection models,\n                      <jats:italic toggle=\"yes\">Galleria mellonella<\/jats:italic>\n                      and a neutropenic mouse oral aspiration pneumonia model.\n                      <jats:italic toggle=\"yes\">S. maltophilia<\/jats:italic>\n                      MICs were significantly lower for ceftazidime in nutritionally deficient media that better corresponds to the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      environment than conventional rich media, resulting in a high percentage of strains determined resistant in traditional media being determined susceptible in nutritionally deficient media. The addition of zinc and manganese to the deficient media abrogated this difference, which was dependent on the L1 metallo-\u03b2-lactamase (MBL). Ceftazidime protected both\n                      <jats:italic toggle=\"yes\">G. mellonella<\/jats:italic>\n                      and neutropenic mice against lethal infection caused by\n                      <jats:italic toggle=\"yes\">S. maltophilia<\/jats:italic>\n                      that was predicted to be resistant in traditional media but susceptible in nutrient-deficient media. Ceftazidime may remain a viable therapeutic option for patients with\n                      <jats:italic toggle=\"yes\">S. maltophilia<\/jats:italic>\n                      infection caused by strains predicted to be resistant by traditional susceptibility testing. Sequestration of trace metals in the host environment may prevent\n                      <jats:italic toggle=\"yes\">S. maltophilia<\/jats:italic>\n                      MBL activity against ceftazidime.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Breakpoint interpretation criteria for ceftazidime against\n                        <jats:italic toggle=\"yes\">S. maltophilia<\/jats:italic>\n                        were recently removed by CLSI and the FDA. It was noted that clinical data were insufficient to validate the current breakpoints. Clinical data were mixed, with some studies reporting treatment success, but others reporting treatment failure. We believe that antimicrobial testing is suboptimal, and improved testing strategies, such as the use of zinc-limited media for culture, will better model the activity of ceftazidime\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        . Improved susceptibility testing strategies may better discriminate against those isolates that are truly resistant from those that were previously falsely identified as being resistant using conventional testing methods.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00840-24","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T09:01:41Z","timestamp":1747904501000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Ceftazidime retains\n                    <i>in vivo<\/i>\n                    efficacy against strains of\n                    <i>Stenotrophomonas maltophilia<\/i>\n                    for which traditional testing predicts resistance"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9329-5455","authenticated-orcid":false,"given":"Matthew C.","family":"Phillips","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital","place":["Boston, USA"]},{"name":"Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bosul","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Miller","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Goy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marl\u00e8ne","family":"Maeusli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Lam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Spellberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Spellberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"She","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope","place":["Duarte, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Spellberg","sequence":"additional","affiliation":[{"name":"Los Angeles General Hospital","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-4551","authenticated-orcid":false,"given":"Brian","family":"Luna","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"CDC. 2019. 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