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

Abstract

The in vivo efficacy of ceftaroline and rifampin alone or in combination was investigated in an experimental rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteomyelitis. After a 3-day treatment, the mean tibial bacterial load was significantly reduced in animals receiving rifampin alone or combined with ceftaroline (1.89 and 1.68 log 10 CFU/g, respectively, P < 0.0001), whereas ceftaroline alone did not show any significant reduction at this early stage. After a 7-day treatment, the mean tibial bacterial load was reduced for ceftaroline alone compared to control animals (3.6 log 10 CFU/g versus 4.4 log 10 CFU/g, respectively, P < 0.05) and reached the limit of detection in almost all animals receiving rifampin alone or combined with ceftaroline ( P < 0.0001). Finally, after a 14-day treatment the efficacy of ceftaroline alone was enhanced ( P < 0.0001), and no MRSE was recovered from the tibias of animals receiving rifampin alone or combined with ceftaroline. No emergence of rifampin resistance was observed, regardless of the treatment group (monotherapy or combined therapy) or the timepoint of interest. Ceftaroline administered with rifampin could represent a valuable therapeutic option in the management of MRSE osteomyelitis. IMPORTANCE 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.