{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:50:37Z","timestamp":1782280237854,"version":"3.54.5"},"posted":{"date-parts":[[2025,4,9]]},"group-title":"Microbiology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Mycobacteroides abscessus<\/jats:italic>\n                    are rapidly growing non-tuberculous mycobacteria that cause chronic lung and soft tissue infections. Treatment options are often severely limited due to intrinsic resistance to most antimicrobials. Amikacin has historically been a mainstay of combination treatment regimens. However, irreversible hearing loss and vestibular toxicity have led to a search for alternative agents. Apramycin is a novel aminoglycoside currently in phase I clinical trials that may offer lower potential for ototoxic and renal toxic side effects.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>\n                    The goal of this study was to compare apramycin\u2019s\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity with amikacin and other aminoglycosides against a large collection of\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    clinical isolates, both alone and in combination with clofazimine or linezolid. We also tested the activity of apramycin against a more limited collection of other species of rapidly growing mycobacteria.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Analysis was performed using reference broth microdilution minimal inhibitory concentration testing, inkjet printer-assisted checkerboard assays, and time-kill assays.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Against\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    , the MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    for apramycin (2 \u00b5g\/mL) was 8-fold lower than for amikacin (16 \u00b5g\/mL). Plazomicin was inactive, and organisms were rarely susceptible to tobramycin. Synergy was not detected by checkerboard assay. In time-kill studies, clofazimine modestly potentiated activity of apramycin and. to a lesser extent, amikacin. Apramycin and amikacin showed delayed bacterial killing that either achieved or approached a bactericidal threshold. Apramycin was similarly potent against other rapidly growing mycobacteria tested.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Apramycin exhibits more potent\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity against a diverse set of\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    and other rapidly growing mycobacteria than approved aminoglycosides.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.09.648020","type":"posted-content","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T23:05:16Z","timestamp":1744239916000},"source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Activity of Apramycin and Apramycin-Based Combinations Against\n                  <i>Mycobacteroides abscessus<\/i>"],"prefix":"10.64898","author":[{"given":"Yanqin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Truelson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella A.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"O\u2019Doherty","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0392-4500","authenticated-orcid":false,"given":"James E.","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041203352149000_2025.04.09.648020v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz221"},{"key":"2026041203352149000_2025.04.09.648020v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku431"},{"key":"2026041203352149000_2025.04.09.648020v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1125"},{"key":"2026041203352149000_2025.04.09.648020v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103652"},{"key":"2026041203352149000_2025.04.09.648020v1.5","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.29.771"},{"key":"2026041203352149000_2025.04.09.648020v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2006.11.006"},{"key":"2026041203352149000_2025.04.09.648020v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204073109"},{"key":"2026041203352149000_2025.04.09.648020v1.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3430-12.2013"},{"key":"2026041203352149000_2025.04.09.648020v1.9","unstructured":"Company EP . 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