Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA

Maria Celeste Varela, Melanie Roch, Agustina Taglialegna, Scott W. Long, Matthew Ojeda Saavedra, Warren E. Rose, James J. Davis, Lucas R. Hoffman, Rafael E. Hernandez, Roberto R. Rosato, Adriana E. Rosato

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S. aureus isolates from CF sputum samples collected at three US centers between 2015–2018. Molecular relationships demonstrated that high-level resistance of preceding isolates to carbapenems were associated with subsequent isolation of ceftaroline resistant CF MRSA. In vitro evolution experiments showed that pre-exposure of CF MRSA to meropenem with further selection with ceftaroline implied mutations in mecA and additional mutations in pbp1 and pbp2, targets of carbapenems; no effects were achieved by other β-lactams. An in vivo pneumonia mouse model showed the potential therapeutic efficacy of ceftaroline/meropenem combination against ceftaroline-resistant CF MRSA infections. Thus, the present findings highlight risk factors and potential therapeutic strategies offering an opportunity to both prevent and address antibiotic resistance in this patient population.

Original languageEnglish (US)
Article number599
JournalCommunications Biology
Volume3
Issue number1
DOIs
StatePublished - Oct 22 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)
  • Medicine(all)

Fingerprint Dive into the research topics of 'Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA'. Together they form a unique fingerprint.

Cite this