{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:06:29Z","timestamp":1785423989371,"version":"3.56.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100006438","name":"Office of the Assistant Secretary for Health","doi-asserted-by":"publisher","award":["W81XWH-19-1-0295"],"award-info":[{"award-number":["W81XWH-19-1-0295"]}],"id":[{"id":"10.13039\/100006438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Increasing rates of antimicrobial resistance require additional safe and effective options for managing difficult-to-treat infections. SPR206 is a next-generation polymyxin with improved\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      safety profiles. This study determined the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity of SPR206 against a diverse collection of gram-negative isolates. SPR206 was tested against 5,179 Enterobacterales,\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Acinetobacter<\/jats:italic>\n                      spp. collected from patients in the United States (US), Europe, Israel, and Turkey. Broth microdilution was performed following the Clinical &amp; Laboratory Standards Institute (CLSI) guidelines, and MIC results interpreted by CLSI, European Committee on Antimicrobial Susceptibility Testing (EUCAST), and United States Food and Drug Administration (US FDA) criteria. SPR206 (MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      , 0.25\/0.25\u20130.5 mg\/L) was active against\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      , including the multidrug-resistant, extensively drug-resistant, and difficult-to-treat subsets, with 99.8\u2013100% of isolates inhibited at MIC values of \u22642 mg\/L. SPR206 inhibited 94.5% of\n                      <jats:italic toggle=\"yes\">Acinetobacter<\/jats:italic>\n                      spp., including 90.4 and 87.9% of the multidrug-resistant (MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      , 0.12\/2 mg\/L) and extensively drug-resistant (MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      , 0.12\/8 mg\/L) subsets at MIC values of \u22642 mg\/L. SPR206 (MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      , 0.06\/0.25 mg\/L) inhibited 95.4% of non-Morganellaceae Enterobacterales at MIC values of \u22642 mg\/L. SPR206 MIC\n                      <jats:sub>50<\/jats:sub>\n                      and MIC\n                      <jats:sub>90<\/jats:sub>\n                      values of 0.06 and 0.5 mg\/L were obtained against carbapenem-resistant Enterobacterales from the US and Western Europe, whereas MIC\n                      <jats:sub>50<\/jats:sub>\n                      of 0.5 mg\/L and MIC\n                      <jats:sub>90<\/jats:sub>\n                      of 64 mg\/L were noted against carbapenem-resistant Enterobacterales isolates from Eastern Europe. SPR206 demonstrated potent activity against a large collection of gram-negative organisms, including resistant subsets. These results, along with an enhanced safety profile, warrant the development of SPR206 as a candidate for the treatment of infections caused by gram-negative bacteria.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        SPR206 is a novel, next-generation polymyxin with improved safety profiles that demonstrates activity against gram-negative organisms. This study benchmarks the activity and spectrum of SPR206 against a large collection of gram-negative isolates, including multidrug-resistant and extensively drug-resistant\n                        <jats:italic toggle=\"yes\">Acinetobacter<\/jats:italic>\n                        spp. and\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        , and carbapenem-resistant Enterobacterales collected from multiple medical sites in the US and Europe. Additional treatment options are needed as antimicrobial resistance emerges and spreads. The results presented in this manuscript show potent SPR206 activity against resistant and difficult-to-treat gram-negative organisms.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01341-25","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T13:06:26Z","timestamp":1757509586000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    activity of SPR206 and comparator agents against\n                    <i>Pseudomonas aeruginosa<\/i>\n                    ,\n                    <i>Acinetobacter<\/i>\n                    species, and Enterobacterales responsible for infection in United States, European, Israeli, and Turkish hospitals"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-1657","authenticated-orcid":false,"given":"Gina M.","family":"Morgan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0981-0758","authenticated-orcid":true,"given":"Ian","family":"Critchley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05fxq1221","id-type":"ROR","asserted-by":"publisher"}],"name":"Spero Therapeutics","place":["Cambridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-4176","authenticated-orcid":true,"given":"Nicole","family":"Cotroneo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05fxq1221","id-type":"ROR","asserted-by":"publisher"}],"name":"Spero Therapeutics","place":["Cambridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-6644","authenticated-orcid":true,"given":"Helio","family":"Sader","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-1137","authenticated-orcid":true,"given":"Rodrigo","family":"Mendes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"JMI Laboratories\/Element Materials Technology","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO. 2022. 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In vitro bactericidal activity of next-generation polymyxin SPR206 against susceptible and multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae as compared to levofloxacin and meropenem. ASM Microbe, San Francisco, CA"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa217"},{"key":"e_1_3_2_17_2","volume-title":"ECCMID","author":"Grosser L","unstructured":"Grosser L, Heang K, Teague J, Warn P, Corbett D, Dawson MJ. In vivo efficacy of SPR206 in murine lung and thigh infection models caused by multidrug resistant pathogens Pseudomonas aeruginosa and Acinetobacter baumannii. 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