Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
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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.
Originalsprog | Engelsk |
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Artikelnummer | 6479 |
Tidsskrift | Nature Communications |
Vol/bind | 14 |
Udgave nummer | 1 |
Antal sider | 12 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This work was supported by the Wellcome Trust under Grant 220540/Z/20/A (E.M.H.). We thank Frederikke Rosenborg Petersen and Emilie Due Jensen for technical assistance during the animal experiments.
Publisher Copyright:
© 2023, Springer Nature Limited.
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