{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:39:22Z","timestamp":1791841162380,"version":"4.3.4"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Nystatin, a polyene, is one of the oldest antifungal drugs with wide\n              <jats:italic>in vitro<\/jats:italic>\n              potency. BSG005 is a novel, chemically modified, nystatin-like molecule in development for systemic therapy. We evaluated the pharmacokinetic\/pharmacodynamic (PK\/PD) relationships and target exposures using\n              <jats:italic>in vivo<\/jats:italic>\n              invasive pulmonary aspergillosis (IPA) and invasive candidiasis (IC) infection models for BSG005 against common fungal pathogens including\n              <jats:italic>Aspergillus fumigatus<\/jats:italic>\n              ,\n              <jats:italic>Candida albicans<\/jats:italic>\n              ,\n              <jats:italic>Candida auris<\/jats:italic>\n              , and\n              <jats:italic>Candida glabrata<\/jats:italic>\n              . For each species group, three to four strains were selected. Minimum inhibitory concentration (MIC) testing was done by Clinical Laboratory Standards Institute (CLSI) methods. Single-dose kinetics for BSG005 were performed at four dose levels. The immunosuppressed mouse IPA model was used for\n              <jats:italic>A. fumigatus<\/jats:italic>\n              studies. For all\n              <jats:italic>Candida<\/jats:italic>\n              studies, we utilized the neutropenic disseminated candidiasis model. We used quantitative PCR to enumerate\n              <jats:italic>Aspergillus<\/jats:italic>\n              in the lung and colony forming units (CFU) counts for\n              <jats:italic>Candida<\/jats:italic>\n              in the kidney. Treatment results were evaluated based on both area under the concentration-time curve (AUC)\/MIC and maximum plasma concentration (\n              <jats:italic>C<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              )\/MIC exposures. The BSG005 MIC was 1 mg\/L against all strains. Escalating doses of BSG005 resulted in increased effect and, in general, the dose-response curves within each species were concordant. The median 96-h AUC\/MIC associated with net stasis was lowest at 6.08 for\n              <jats:italic>C. glabrata<\/jats:italic>\n              . Increasing exposures were needed for same outcome for\n              <jats:italic>C. auris<\/jats:italic>\n              at 18.7,\n              <jats:italic>C. albicans<\/jats:italic>\n              at 29.3, and\n              <jats:italic>A. fumigatus<\/jats:italic>\n              at 102.4.\n              <jats:italic>C<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              \/MIC targets for the four groups were 0.22, 0.48, 0.60, and 1.41. BSG005 demonstrated potent activity against a variety of fungal pathogens in the neutropenic mouse models.\n              <jats:italic>C<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              \/MIC PK\/PD targets were numerically lower than other polyene studies using the same infection models.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01234-24","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T13:00:38Z","timestamp":1730206838000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["<i>In vivo<\/i>\n            pharmacodynamic evaluation of the novel nystatin derivative BSG005 in the invasive candidiasis and invasive pulmonary aspergillosis mouse models"],"prefix":"10.1128","volume":"68","author":[{"given":"Alexander J.","family":"Lepak","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Massey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-1500","authenticated-orcid":true,"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine K.","family":"Olesen","sequence":"additional","affiliation":[{"name":"Biosergen AS","place":["Trondheim, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryley","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":true,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin","place":["Madison, USA"]},{"name":"William S. 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