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05:02

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Published on: February 10, 2011

Activity of ceftaroline against Enterococcus faecium PBP5

Xavier Henry1, Oliver Verlaine, Ana Amoroso

  • 1Bacterial Physiology and Genetics Unit, Center for Protein Engineering, Life Science Department, University of Liège, Liège, Belgium.

Antimicrobial Agents and Chemotherapy
|September 25, 2013
PubMed

Insights

Ceftaroline effectively kills ampicillin-resistant Enterococcus faecium by rapidly inactivating the essential PBP5 protein. This finding offers new insights into treating resistant bacterial infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Enterococcus faecium is an opportunistic pathogen often resistant to beta-lactam antibiotics.
  • Penicillin-binding protein 5 (PBP5) in E. faecium has low affinity for beta-lactams and is often mutated in resistant strains.
  • Ceftaroline has shown limited efficacy against beta-lactam-resistant E. faecium previously.

Purpose of the Study:

  • To investigate the activity of ceftaroline against a laboratory-derived ampicillin-resistant E. faecium mutant.
  • To determine the interaction of ceftaroline with PBP5 in this resistant strain.

Main Methods:

  • Construction of an ampicillin-resistant E. faecium mutant overproducing wild-type PBP5.
  • Assessment of ceftaroline's killing activity against the mutant strain.
  • Comparison of PBP5 inactivation rates by ceftaroline, benzylpenicillin, and ceftobiprole.

Main Results:

  • Ceftaroline demonstrated significant killing activity against the ampicillin-resistant E. faecium mutant.
  • Ceftaroline inactivated PBP5 more rapidly than benzylpenicillin.
  • Ceftaroline also inactivated PBP5 faster than ceftobiprole.

Conclusions:

  • Ceftaroline exhibits potent bactericidal activity against ampicillin-resistant E. faecium strains.
  • Rapid inactivation of PBP5 is the mechanism by which ceftaroline exerts its killing effect.
  • These findings suggest potential for ceftaroline in treating E. faecium infections, even those with beta-lactam resistance.

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