{
  "abstract": "Objectives: Aminoglycosides are often combined with β-lactams for the treatment of carbapenem-resistant Enterobacterales, but the impact of aminoglycoside-modifying enzyme (AME) genes on treatment efficacy in phenotypically susceptible isolates remains unclear. We evaluated whether aac(6′)-Ib-cr, the AME gene with recognized activity against amikacin, attenuates amikacin efficacy in KPC-producing Klebsiella pneumoniae.\n\nMethods: Thirteen clinical isolates of KPC-producing K. pneumoniae without phenotypic aminoglycoside resistance (amikacin MIC ≤4 mg/L; median 2, range 0.5–3 mg/L) were studied. Three were AME-negative; 10 were AME-positive, carrying aac(6′)-Ib-cr, aac(3)-IIa and strA/strB. Amikacin activity was assessed by time-kill assays and a Galleria mellonella survival model, compared with ceftazidime–avibactam.\n\nResults: In time-kill assays, amikacin killing at 24 h was greater in AME-negative isolates than in AME-positive isolates (mean 4.28 ± 1.30 versus 2.41 ± 2.16 log10 cfu/mL), with more regrowth by 72 h in AME-positive isolates (median 1.94 [0–5.82] versus 0 [0–3.32] log10). In the survival model, amikacin reduced larval mortality versus saline (HR, 0.32; 95% CI, 0.24–0.43; P < 0.001). The interaction between AME-positive status and amikacin (HR, 2.11; 95% CI, 1.54–2.90; P < 0.001) indicated reduced efficacy that persisted after adjustment for amikacin MIC (adjusted HR, 2.09; 95% CI, 1.52–2.86; P < 0.001). Ceftazidime–avibactam reduced mortality (HR, 0.24; 95% CI, 0.18–0.33; P < 0.001) with no significant interaction with AME gene status (HR, 1.03; 95% CI, 0.71–1.48; P = 0.894).\n\nConclusion: Carriage of aac(6′)-Ib-cr was associated with reduced amikacin efficacy despite phenotypic susceptibility, independently of amikacin MIC, consistent with a treatment effect modifier rather than a binary resistance determinant. Genotyping of aac(6′)-Ib-cr may help guide aminoglycoside use in carbapenem-resistant Klebsiella pneumoniae infections.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Jaehoon Kim",
      "orcid": "0009-0000-6290-8696"
    },
    {
      "name": "Jae Eun Seong"
    },
    {
      "name": "Youn-Jung Lee"
    },
    {
      "name": "Sora Park"
    },
    {
      "name": "Min Han"
    },
    {
      "name": "Yongseop Lee"
    },
    {
      "name": "Jung Ah Lee"
    },
    {
      "name": "Jung Ho Kim",
      "orcid": "0000-0002-5033-3482"
    },
    {
      "name": "Jin Young Ahn",
      "orcid": "0000-0002-3740-2826"
    },
    {
      "name": "Su Jin Jeong"
    },
    {
      "name": "Nam Su Ku",
      "orcid": "0000-0002-9717-4327"
    },
    {
      "name": "Joon-Sup Yeom"
    },
    {
      "name": "Hyukmin Lee"
    },
    {
      "name": "Jun Yong Choi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dgfepswb4vsy4.bib",
  "cited_by": 0,
  "doi": "10.1093/jacamr/dlag239",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724272/?tool=EBI",
  "id": "dgfepswb4vsy4",
  "issns": [
    "2632-1823"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13724272",
  "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": [
    [
      "heading",
      "AcademicSubjects/MED00740"
    ],
    [
      "heading",
      "AcademicSubjects/SCI01150"
    ],
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1313|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7225127371",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724272/pdf/?tool=EBI",
  "pmcid": "PMC13724272",
  "pmid": "42973457",
  "published": "2026-11-02",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/dgfepswb4vsy4.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC13724272",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13724272"
    },
    {
      "first_seen": "2026-11-04T12:22:52Z",
      "native_id": "PMC13724272",
      "source": "pmc",
      "url": "https://doi.org/10.1093/jacamr/dlag239"
    },
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42973457",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42973457"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1313|Antibiotic Resistance in Bacteria",
      "subfield": "general"
    }
  ],
  "title": "Amikacin activity against carbapenem-resistant Klebsiella pneumoniae without phenotypic aminoglycoside resistance: impact of aminoglycoside-modifying enzyme (AME) gene aac(6′)-Ib-cr in vitro and in vivo",
  "title_text": "Amikacin activity against carbapenem-resistant Klebsiella pneumoniae without phenotypic aminoglycoside resistance: impact of aminoglycoside-modifying enzyme (AME) gene aac(6′)-Ib-cr in vitro and in vivo",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:49Z",
  "url": "https://research.draconitic.com/paper/dgfepswb4vsy4",
  "venue": "JAC-antimicrobial resistance",
  "versions": []
}