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

Autor: Maria Celeste Varela, Roberto R. Rosato, Matthew Ojeda Saavedra, Agustina Taglialegna, James J. Davis, Melanie Roch, Scott Wesley Long, Adriana E. Rosato, Rafael E Hernandez, Lucas R. Hoffman, Warren E. Rose
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Methicillin-Resistant Staphylococcus aureus
Cystic Fibrosis
medicine.drug_class
030106 microbiology
Cephalosporin
Medicine (miscellaneous)
Microbial Sensitivity Tests
medicine.disease_cause
Cystic fibrosis
Meropenem
Microbiology
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Antibiotic resistance
Bacterial Proteins
Drug Resistance
Multiple
Bacterial
medicine
polycyclic compounds
Humans
lcsh:QH301-705.5
business.industry
Respiratory disease
Staphylococcal Infections
biochemical phenomena
metabolism
and nutrition
medicine.disease
bacterial infections and mycoses
Anti-Bacterial Agents
Cephalosporins
Pneumonia
030104 developmental biology
Carbapenems
lcsh:Biology (General)
Staphylococcus aureus
Preclinical research
Mutation
Sputum
Drug Therapy
Combination
medicine.symptom
General Agricultural and Biological Sciences
business
Genome
Bacterial
medicine.drug
Zdroj: Communications Biology, Vol 3, Iss 1, Pp 1-10 (2020)
Communications Biology
ISSN: 2399-3642
Popis: 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.
Varela, Roch et al. find that resistance of preceding isolates to carbapenems is associated with the subsequent isolation of methicillin-resistant Staphylococcus aureus (MRSA) resistant to ceftaroline. Addition of meropenem reduces the cystic fibrosis MRSA’s resistance to ceftaroline in a pneumonia mouse model, suggesting a strategy to control antibiotics resistance.
Databáze: OpenAIRE
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