{
  "abstract": "Linezolid is a key component of the bedaquiline, pretomanid, linezolid (BPaL) regimen for rifampin-resistant tuberculosis, but dose- and duration-dependent mitochondrial toxicity frequently limits its use. TBD09 (formerly MK-7762) is a novel oxazolidinone developed to maintain antitubercular potency comparable to linezolid while reducing related adverse events. We evaluated the contribution of TBD09 to the bactericidal and sterilizing activities of BPa-based regimens in a murine tuberculosis model. BALB/c mice were aerosol-infected with Mycobacterium tuberculosis H37Rv and treated starting 2 weeks post-infection. In Experiment 1, dose-ranging bactericidal activity of TBD09 (50, 100, 200 mg/kg) was assessed alone and in combination with BPa, with comparison to linezolid and sutezolid. In Experiment 2, the sterilizing activity of TBD09 (200 mg/kg) in combination with BPa and BPa plus moxifloxacin (M) was assessed by evaluating relapse after treatment durations of 4-22 weeks. TBD09 monotherapy was bacteriostatic, similar to linezolid over the first 4 weeks of treatment. The addition of TBD09 to BPa significantly enhanced bactericidal activity comparable to the addition of linezolid. In relapse assessments, BPa+TBD09 resulted in significantly fewer relapses compared to BPa alone after 14 weeks of treatment, and BPaM+TBD09 resulted in significantly fewer relapses compared to BPaM after 10 weeks. Model-based analysis estimated the treatment duration to 95% cure for BPa+TBD09 at 2.7 weeks, compared to 3.2 weeks for BPaL, although the time to 50% cure was similar. These results demonstrate that TBD09 provides bactericidal and sterilizing activity similar to linezolid in combination with BPa(M), supporting further clinical development of TBD09 for tuberculosis.",
  "abstract_shown": true,
  "affiliations": [
    "Johns Hopkins University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "D. V. Almeida"
    },
    {
      "name": "P. J. Converse"
    },
    {
      "name": "C. Schill"
    },
    {
      "name": "J. I. Lee"
    },
    {
      "name": "M. Levi"
    },
    {
      "name": "A. Berg"
    },
    {
      "name": "M. Khisi"
    },
    {
      "affs": [
        0
      ],
      "name": "E. L. Nuermberger"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/da6x4ry0723fq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753971",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753971v1.full",
  "id": "da6x4ry0723fq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753971v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7214229903",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753971v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/da6x4ry0723fq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:23Z",
      "native_id": "10.64898/2026.09.23.753971",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753971v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Contribution of the novel oxazolidinone TBD09 (MK-7762) to regimens with bedaquiline and pretomanid in a mouse model of tuberculosis",
  "title_text": "Contribution of the novel oxazolidinone TBD09 (MK-7762) to regimens with bedaquiline and pretomanid in a mouse model of tuberculosis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:23Z",
  "url": "https://research.draconitic.com/paper/da6x4ry0723fq",
  "venue": "bioRxiv",
  "versions": []
}