{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:43:03Z","timestamp":1792417383552,"version":"4.4.0"},"reference-count":30,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Fosmanogepix (prodrug of manogepix) is a novel antifungal agent targeting the Gwt1 enzyme. This agent has activity against a diverse spectrum of fungal species, including species refractory to other antifungal classes or multidrug-resistant fungi. A total of 332 molds from a worldwide surveillance study were susceptibility tested for manogepix and comparator antifungal agents by the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. Wild-type upper limit (WT-UL) values were determined for manogepix against organism groups using cumulative surveillance data. Isolates were collected from 20 countries, 41 hospitals, and 7 different infection sources. Eighteen genera were represented. Isolates included 208 non-\n                      <jats:italic toggle=\"yes\">fumigatus Aspergillus<\/jats:italic>\n                      spp.; 37.3% (124 isolates) were non-\n                      <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                      molds. The manogepix minimum effective concentration (MEC\n                      <jats:sub>50\/90<\/jats:sub>\n                      ) was lower than the MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      for azole comparators or amphotericin B against all\n                      <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                      spp.,\n                      <jats:italic toggle=\"yes\">Fusarium<\/jats:italic>\n                      spp.,\n                      <jats:italic toggle=\"yes\">Scedosporium<\/jats:italic>\n                      spp.,\n                      <jats:italic toggle=\"yes\">Lomentospora<\/jats:italic>\n                      spp.,\n                      <jats:italic toggle=\"yes\">Mucor<\/jats:italic>\n                      spp., and\n                      <jats:italic toggle=\"yes\">Penicillium<\/jats:italic>\n                      spp. Only\n                      <jats:italic toggle=\"yes\">Rhizopus<\/jats:italic>\n                      spp. had higher MEC\n                      <jats:sub>50\/90<\/jats:sub>\n                      values for manogepix than the MIC\n                      <jats:sub>50\/90<\/jats:sub>\n                      values of the comparators. The WT-UL values reflected this, with the highest values for\n                      <jats:italic toggle=\"yes\">Rhizopus<\/jats:italic>\n                      spp. at 16 mg\/L and\n                      <jats:italic toggle=\"yes\">Mucor<\/jats:italic>\n                      spp. at 4 mg\/L, while they were \u22640.12 mg\/L for all other organisms. Between 2023 and 2024, there were no organisms with MECs for manogepix above the WT-UL value. Manogepix displayed robust\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity against contemporary non-\n                      <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                      mold isolates. This agent was more potent than azole comparators or amphotericin B against most organism groups. Historically, less than 5% of isolates tested (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 19) had MECs above the WT-UL cutoff values. These data support the continued development of manogepix for the treatment of mold infections.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Fosmanogepix (prodrug of manogepix) is a novel antifungal agent with a new mechanism of action and broad-spectrum activity, including against yeasts and molds. It is currently in two Phase 3 clinical trials for the treatment of invasive candidiasis and invasive mold infections and has previously been used for the treatment of\n                        <jats:italic toggle=\"yes\">Fusarium<\/jats:italic>\n                        spp. infections during an outbreak. There are three main antifungal classes (echinocandins, azoles, and polyenes), but only azoles and amphotericin B have activity against non-\n                        <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                        molds; therefore, novel antifungal agents are urgently needed because invasive fungal infections have high morbidity and mortality rates. Here, we look at the\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        activity of manogepix and comparator antifungal agents against non-\n                        <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                        mold isolates collected from patient infections in 2023 and 2024. Manogepix showed potent\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        activity against these organisms, with similar to or better activity than that of the comparators against most organism groups, and represents a promising potential future treatment option.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02559-26","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:00:50Z","timestamp":1792414850000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Activity of manogepix and comparator antifungal agents against uncommon filamentous fungal isolates collected in a global surveillance program"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9785-5034","authenticated-orcid":true,"given":"Marisa L.","family":"Winkler","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby","family":"Klauer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Edeker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley","family":"Fedler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-7653","authenticated-orcid":true,"given":"Paul","family":"Rhomberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1782","authenticated-orcid":true,"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof6010028"},{"key":"e_1_3_4_3_2","unstructured":"Antifungal Agents. 2025. 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