Therapeutic potential of dalbavancin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-osteomyelitis

Abstract

Bacterial osteomyelitis is a major clinical challenge in human and veterinary patients. This infection is an infrequent but feared complication of orthopedic surgery and is mainly caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of dalbavancin (dosed for either 7 or 14 days) in an MRSA-osteomyelitis tibial bone model. A total of 39 rats were included in the study. All animals received an inoculum of a clinical strain of MRSA (106 colony-forming units [CFU]) injected into the proximal tibia under general anesthesia. Dalbavancin was injected intraperitoneally for 7 or 14 days in 13 animals each; the remaining 13 animals received saline solution. After treatment, the animals were sacrificed. Infected tibiae were recovered for histological evaluation and microbiological analysis (MRSA count per gram of bone). Rats that received dalbavancin showed a statistically significant reduction of MRSA counts compared with the control group: median 0 CFU/g bone (14 days of dalbavancin) vs. 70 CFU/g bone (7 days of dalbavancin) and 1600 CFU/g bone (control). Histological evaluation showed typical signs of osteomyelitis in the control group, whereas there were no signs of bone infection in 92% of the rats that received 14 days of dalbavancin. According to this model, dalbavancin seems to have good efficacy for treating serious Gram-positive bone infections, including those caused by MRSA.