Efficacy of ceftaroline versus vancomycin in an experimental foreign-body and systemic infection model caused by biofilm-producing methicillin-resistant Staphylococcus epidermidis

Int J Antimicrob Agents. 2016 Dec;48(6):661-665. doi: 10.1016/j.ijantimicag.2016.09.011. Epub 2016 Oct 18.

Abstract

In this study, the efficacy of ceftaroline versus vancomycin against biofilm-producing methicillin-resistant Staphylococcus epidermidis (MRSE) in a murine model of foreign-body and systemic infection was compared. Two bacteraemic biofilm-producing MRSE strains were used (SE284 and SE385). The minimum inhibitory concentrations (MICs) for strains SE284 and SE385, were, respectively, 0.25 mg/L and 0.5 mg/L for ceftaroline and 4 mg/L and 2 mg/L for vancomycin. The in vitro bactericidal activities of ceftaroline and vancomycin were evaluated using time-kill curves. A foreign-body and systemic infection model in neutropenic female C57BL/6 mice was used to ascertain in vivo efficacy. Animals were randomly allocated into three groups (n = 15) without treatment (controls) or treated with ceftaroline 50 mg/kg every 8 h or vancomycin 110 mg/kg every 6 h. In vitro, ceftaroline showed concentration-dependent bactericidal activity, whilst vancomycin presented time-dependent activity. In the experimental in vivo model, ceftaroline and vancomycin decreased the liver and catheter bacterial concentrations (P <0.05) and increased survival (P <0.05) for both strains. In conclusion, ceftaroline is as effective as vancomycin in the treatment of experimental foreign-body and systemic infection caused by biofilm-producing MRSE.

Keywords: Foreign-body infection; MRSE; Pharmacodynamics; Pharmacokinetics; Systemic infection.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Load
  • Biofilms / drug effects
  • Ceftaroline
  • Cephalosporins / therapeutic use*
  • Disease Models, Animal
  • Female
  • Foreign Bodies / complications
  • Methicillin Resistance
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Random Allocation
  • Sepsis / drug therapy*
  • Sepsis / microbiology
  • Soft Tissue Infections / drug therapy*
  • Soft Tissue Infections / microbiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus epidermidis / drug effects*
  • Staphylococcus epidermidis / isolation & purification
  • Treatment Outcome
  • Vancomycin / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Vancomycin