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 |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |