{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:54:14Z","timestamp":1791374054346,"version":"4.3.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech, Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Safe and effective therapies are needed for hospitalized patients with complicated Staphylococcus aureus infections, including approaches capable of eradicating intracellular bacterial reservoirs that contribute to treatment failure. This study evaluated the safety, tolerability, and pharmacokinetics of DSTA4637S, an antibody\u2013antibiotic conjugate combining an anti-S. aureus antibody with a rifamycin-class antibiotic, in patients with complicated S. aureus bacteremia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this phase 1b, randomized, double-blind, placebo-controlled study, 25 patients with methicillin-sensitive (MSSA, 68%) or -resistant (MRSA, 32%) complicated S. aureus bacteremia received weekly intravenous doses of DSTA4637S at 15, 45, or 100\u2005mg\/kg in combination with at least 4 weeks of standard-of-care antistaphylococcal antibiotics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most patients (92%) experienced \u22651 treatment-emergent adverse event (TEAE), of which 44% were considered treatment-related. Grade \u22653 TEAEs and serious adverse events occurred in 72% and 56% of patients, respectively. The most common grade \u22653 TEAEs were infusion-related reactions (IRRs), pneumonia, anemia, and respiratory failure. Four patients (21%) receiving DSTA4637S discontinued study treatment due to treatment-related IRRs. Systemic exposure of DSTA4637S in patients increased approximately dose-proportionally from 15 to 100\u2005mg\/kg but was 30%\u201360% lower than previously observed in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The safety profile of DSTA4637S, characterized by unpredictable IRRs, and its pharmacokinetic behavior in patients differed substantially from those observed in healthy volunteers, highlighting the critical importance of conducting early phase studies in the target patient population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag608","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:22:07Z","timestamp":1790335327000},"source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients With Complicated\n                    <i>Staphylococcus aureus<\/i>\n                    Bacteremia Receiving Standard-of-Care Antibiotics"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0487-1711","authenticated-orcid":false,"given":"Loren G","family":"Miller","sequence":"first","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, and Harbor-UCLA Medical Center Division of Infectious Diseases, , Torrance, California ,","place":["USA"]},{"name":"David Geffen School of Medicine at UCLA Division of Infectious Diseases, , Los Angeles, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vance G","family":"Fowler","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine Department of Medicine, , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8057-7755","authenticated-orcid":false,"given":"Jose M","family":"Miro","sequence":"additional","affiliation":[{"name":"Hospital Clinic-IDIBAPS, University of Barcelona, and Reial Academia de Medicina de Catalunya (RAMC) , Barcelona ,","place":["Spain"]},{"name":"CIBERINFEC, Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Horcajada","sequence":"additional","affiliation":[{"name":"Hospital del Mar Department of Infectious Diseases, , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Lewin-Koh","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Department of Early Clinical Development, , South San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Chu","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Department of Early Clinical Development, , South San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Rymut","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Department of Early Clinical Development, , South San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Department of Early Clinical Development, , South San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie M","family":"Rosenberger","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Department of Early Clinical Development, , South San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter L W","family":"Hazenbos","sequence":"additional","affiliation":[{"name":"Genmab Department of Target Discovery, , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Glickstein","sequence":"additional","affiliation":[{"name":"Genentech, Inc. 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