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

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Raisen, Claire L 
Vingsbo Lundberg, Carina 


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.


Acknowledgements: 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.


Humans, Penicillins, beta-Lactamase Inhibitors, Staphylococcus epidermidis, Staphylococcal Infections, Clavulanic Acid, Amoxicillin, Microbial Sensitivity Tests, Anti-Bacterial Agents

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Nat Commun

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Springer Science and Business Media LLC