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Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages

Author

Listed:
  • Xiaoliang Ba

    (University of Cambridge)

  • Claire L. Raisen

    (University of Cambridge)

  • Olivier Restif

    (University of Cambridge)

  • Lina Maria Cavaco

    (Statens Serum Institut)

  • Carina Vingsbo Lundberg

    (Statens Serum Institut)

  • Jean Y. H. Lee

    (The University of Melbourne at The Doherty Institute for Infection and Immunity)

  • Benjamin P. Howden

    (The University of Melbourne at The Doherty Institute for Infection and Immunity)

  • Mette D. Bartels

    (Copenhagen University Hospital - Amager and Hvidovre
    University of Copenhagen)

  • Birgit Strommenger

    (Robert Koch Institute, Wernigerode Branch)

  • Ewan M. Harrison

    (University of Cambridge
    University of Cambridge
    Wellcome Sanger Institute)

  • Anders Rhod Larsen

    (Statens Serum Institut)

  • Mark A. Holmes

    (University of Cambridge)

  • Jesper Larsen

    (Statens Serum Institut)

Abstract

Global spread of multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages underscores the need for new therapeutic strategies. Here we show that many S. epidermidis isolates belonging to these lineages display cryptic susceptibility to penicillin/β-lactamase inhibitor combinations under in vitro conditions, despite carrying the methicillin resistance gene mecA. Using a mouse thigh model of S. epidermidis infection, we demonstrate that single-dose treatment with amoxicillin/clavulanic acid significantly reduces methicillin-resistant S. epidermidis loads without leading to detectable resistance development. On the other hand, we also show that methicillin-resistant S. epidermidis is capable of developing increased resistance to amoxicillin/clavulanic acid during long-term in vitro exposure to these drugs. These findings suggest that penicillin/β-lactamase inhibitor combinations could be a promising therapeutic candidate for treatment of a high proportion of methicillin-resistant S. epidermidis infections, although the in vivo risk of resistance development needs to be further addressed before they can be incorporated into clinical trials.

Suggested Citation

  • Xiaoliang Ba & Claire L. Raisen & Olivier Restif & Lina Maria Cavaco & Carina Vingsbo Lundberg & Jean Y. H. Lee & Benjamin P. Howden & Mette D. Bartels & Birgit Strommenger & Ewan M. Harrison & Anders, 2023. "Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42245-y
    DOI: 10.1038/s41467-023-42245-y
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