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

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 Rhod Larsen, Mark A. Holmes and Jesper Larsen ()
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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
Birgit Strommenger: Robert Koch Institute, Wernigerode Branch
Ewan M. Harrison: University of Cambridge
Anders Rhod Larsen: Statens Serum Institut
Mark A. Holmes: University of Cambridge
Jesper Larsen: Statens Serum Institut

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42245-y

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