Efficacy of ceftaroline and rifampin, alone or combined, in a rat model of methicillin-resistant Staphylococcus epidermidis osteomyelitis without implant

Microbiol Spectr. 2023 Dec 12;11(6):e0015323. doi: 10.1128/spectrum.00153-23. Epub 2023 Oct 4.

Abstract

Methicillin-resistant Staphylococcus epidermidis (MRSE) contributes to a high percentage of orthopedic infections, and their treatment represents a huge challenge. The present study aimed to evaluate the efficacy of ceftaroline alone or combined with rifampin in a rat MRSE osteomyelitis model and the bone penetration of ceftaroline. A ceftaroline monotherapy showed a significant bacterial reduction in infected bones after a 7-day period of treatment. The combination ceftaroline plus rifampin leveraged rifampin's bactericidal activity, shortening the duration of positive culture in infected animals. These results suggest that ceftaroline and rifampin combination therapy could represent a valuable therapeutic option for human MRSE osteomyelitis and deserves further preclinical and clinical evaluation.

Keywords: MRSE; bone penetration; ceftaroline; osteitis; pharmacokinetics; preclinical model; rifampin.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Humans
  • Methicillin Resistance
  • Methicillin-Resistant Staphylococcus aureus*
  • Osteomyelitis* / drug therapy
  • Osteomyelitis* / microbiology
  • Rats
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Staphylococcal Infections* / drug therapy
  • Staphylococcal Infections* / microbiology
  • Staphylococcus epidermidis
  • Vancomycin / pharmacology

Substances

  • Rifampin
  • Anti-Bacterial Agents
  • Vancomycin