학술논문
Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages.
Document Type
Academic Journal
Author
Ba X; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Raisen CL; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Restif O; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Cavaco LM; Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.; Vingsbo Lundberg C; Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.; Lee JYH; Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.; Howden BP; Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.; Bartels MD; Department of Clinical Microbiology, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Strommenger B; National Reference Centre for Staphylococci and Enterococci, Division Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode Branch, Wernigerode, Germany.; Harrison EM; Department of Medicine, University of Cambridge, Cambridge, UK.; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Wellcome Sanger Institute, Hinxton, UK.; Larsen AR; Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.; Holmes MA; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Larsen J; Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark. jrl@ssi.dk.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.
(© 2023. Springer Nature Limited.)
(© 2023. Springer Nature Limited.)