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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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Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
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Journal Article
Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
2023
Overview
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.
Staphylococcus epidermidis
can cause invasive infections that are difficult to treat due to multi-resistance to most clinically relevant drugs, including methicillin and other β-lactam antibiotics, vancomycin, and rifampicin. In this work, the authors use in vitro assays and a mouse infection model to explore cryptic susceptibility and development of resistance to penicillin/β-lactamase combinations.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 64/60
/ Amides
/ Amoxicillin - therapeutic use
/ Anti-Bacterial Agents - pharmacology
/ Anti-Bacterial Agents - therapeutic use
/ beta-Lactamase Inhibitors - pharmacology
/ Clavulanic Acid - pharmacology
/ Clavulanic Acid - therapeutic use
/ Humanities and Social Sciences
/ Humans
/ Multidrug resistant organisms
/ Penicillins - therapeutic use
/ Rifampin
/ Science
/ Staphylococcal Infections - drug therapy
/ Thigh
