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

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.

Fig 1

Ceftaroline mean plasma concentrations after a single 20 mg/kg intraperitoneal dose in healthy rats. The C_max was 20.5 µg/mL at 0.5 h, and the AUC_0-24 using one dose every 12 h was 49.5 µg.h/mL.

Fig 2

Results of quantitative MRSE bone cultures (log10 CFU per gram of bone) from rats receiving vehicle, ceftaroline alone, rifampin alone, or the combined therapy. Individual tibia results are shown for each study group (n = number of tibias, 2 tibias per animal). Results are expressed as mean ± SD. D7: Start of therapy. Quantitative variables were compared using an analysis of variance and a post-hoc analysis using Bonferroni’s test. (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, versus controls).

Fig 3

Experimental design summary.