{
  "abstract": "Background\n\nCarbapenem-resistant Enterobacterales (CRE) represent a major therapeutic challenge, driven in part by serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs). APC24-7 is a broad-spectrum β-lactamase inhibitor (BLI) designed to inhibit enzymes from both groups. Here, we evaluated the ability of APC24-7 to potentiate meropenem (MEM) activity against meropenem-resistant Escherichia coli and Klebsiella pneumoniae.Methods & results\n\nCheckerboard assays were performed against 31 K. pneumoniae and 17 E. coli isolates harboring a range of clinically relevant SBL and/or MBL genes. APC24-7 reduced meropenem minimum inhibitory concentrations (MICs) in an isolate- and concentration-dependent manner. At 32 mg/L APC24-7, meropenem MICs fell within the CLSI susceptible range for meropenem in 11 of 17 E. coli isolates, whereas 16 of 31 K. pneumoniae isolates remained resistant. Time-kill experiments with nine selected isolates showed bactericidal activity under active combination conditions, defined as a ≥3 log10 CFU/mL reduction from the initial bacterial count, within 3-5 h. Pharmacokinetic evaluation in infected mice showed less-than-dose-proportional systemic exposure following subcutaneous administration of APC24-7, with a maximum plasma concentration of approximately 26 mg/L after a 30 mg/kg dose. In a neutropenic murine thigh infection model, APC24-7 increased meropenem activity against four selected in vitro-responsive isolates in a dose-dependent manner.Conclusions\n\nThese findings provide preclinical proof of concept for APC24-7 as a broad-spectrum BLI capable of potentiating meropenem against Enterobacterales harboring diverse β-lactamases, while highlighting substantial isolate-dependent variability that warrants further pharmacokinetic/pharmacodynamic and resistance-mechanism studies.",
  "abstract_shown": true,
  "affiliations": [
    "Bacteria, Parasites & Fungi, Statens Serum Institut (SSI), 2300 Copenhagen, Denmark.",
    "CANDOR Simulation, 8270 Højbjerg, Denmark.",
    "AdjuTec Pharma AS, 0349 Oslo, Norway.",
    "Department of Pharmacy, The University of Oslo, 0371 Oslo, Norway."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carina Sofia Silva Matias",
      "orcid": "0000-0003-2386-9422"
    },
    {
      "affs": [
        1
      ],
      "name": "Klaus Skovbo Jensen",
      "orcid": "0000-0003-0408-6705"
    },
    {
      "affs": [
        0
      ],
      "name": "Henrik Hasman"
    },
    {
      "affs": [
        0
      ],
      "name": "Kasper Thystrup Karstensen",
      "orcid": "0000-0002-5009-0476"
    },
    {
      "affs": [
        2
      ],
      "name": "Bjørg Bolstad",
      "orcid": "0009-0007-9064-932X"
    },
    {
      "affs": [
        2
      ],
      "name": "Bjørn Klem"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Pål Rongved"
    },
    {
      "affs": [
        0
      ],
      "name": "Carina Vingsbo Lundberg"
    },
    {
      "affs": [
        0
      ],
      "name": "Jon Ulf Hansen",
      "orcid": "0000-0002-6410-5755"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dgbm23pg5kekg.bib",
  "cited_by": 0,
  "doi": "10.3390/antibiotics15101011",
  "fulltext_url": "https://europepmc.org/articles/PMC13700718",
  "id": "dgbm23pg5kekg",
  "issns": [
    "2079-6382"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938753",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1313|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7221521461",
  "pdf_url": "https://europepmc.org/articles/PMC13700718?pdf=render",
  "pmcid": "PMC13700718",
  "pmid": "42938753",
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dgbm23pg5kekg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42938753",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938753"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1313|Antibiotic Resistance in Bacteria",
      "subfield": "general"
    }
  ],
  "title": "In Vitro and In Vivo Efficacy of the Broad-Spectrum β-Lactamase Inhibitor APC24-7 in Combination with Meropenem Against Carbapenem-Resistant Enterobacterales.",
  "title_text": "In Vitro and In Vivo Efficacy of the Broad-Spectrum β-Lactamase Inhibitor APC24-7 in Combination with Meropenem Against Carbapenem-Resistant Enterobacterales.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/dgbm23pg5kekg",
  "venue": "Antibiotics (Basel, Switzerland)",
  "versions": []
}