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

Autor: 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 14; Vol. 14 (1), pp. 6479. Date of Electronic Publication: 2023 Oct 14.
DOI: 10.1038/s41467-023-42245-y
Abstrakt: 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.)
Databáze: MEDLINE
Externí odkaz: