Efficacy of dalbavancin against MRSA biofilms in a rat model of orthopaedic implant-associated infection.

OBJECTIVES: The aim of this study was to evaluate the efficacy of dalbavancin against MRSA biofilm-related infection in orthopaedic implants in vivo. METHODS: One MRSA strain isolated from human osteomyelitis was used to promote biofilm formation on the surface of screws. The implants were inserted in the proximal tibia under general anaesthesia. Thirty-nine Wistar rats were divided into three groups [control group (no treatment), Group 1 (7 days of treatment) and Group 2 (14 days of treatment)]; both treatment groups were administered dalbavancin intraperitoneally and euthanized after treatment. cfu of bacteria present in both the tibia and the implant were quantified. The infection severity was assessed by histopathology and scored from 0 (no infection) to 4 (severe infection). RESULTS: The high number of cfu/g and cfu/mL present in the control group indicated a well-established infection. There was a significant reduction in cfu in rats treated with dalbavancin both in the tibia (2.8 × 105 cfu/g) and the implant (1.1 × 106 cfu/mL) in Group 1 (1.8 × 103 cfu/g and 2.4 × 105 cfu/mL, respectively) and in Group 2 (8.2 cfu/g and 8.2 × 103 cfu/mL, respectively). Most animals from the control group presented an infection scored as 3 (severe). At the end of the experiment, most rats from Groups 1 and 2 presented an infection scored as 2 (moderate) and 0 (no infection), respectively. CONCLUSIONS: Although there was a marked decrease in cfu number, signs of biofilm-induced infection prevailed after 14 days of treatment. Further studies should be carried out to evaluate the potential of dalbavancin in the treatment of bone and orthopaedic implant-associated MRSA infections.

Anti-biofilm activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) isolated from human bone infection.

The presence of methicillin-resistant Staphylococcus aureus (MRSA) in bone infections difficults its treatment and is a sign of concern. The aim of this study was to evaluate in vitro activity of dalbavancin on pre-established adhered cells and 24 h old biofilms of MRSA strains isolated from a human bone infection. Thirty-three MRSA were isolated from osteomyelitis episodes. The antimicrobial susceptibility of these strains was assessed by the Kirby-Bauer disc diffusion method and the presence of resistance genes was screened by PCR. MRSA planktonic minimum inhibitory concentration and minimum bactericidal concentration were assessed. Minimum biofilm eradication concentration (MBEC) was performed by the microtiter biofilm formation assay. All 33 MRSA strains were classified as multidrug-resistant strains and susceptible to dalbavancin. Dalbavancin inhibited the growth of 54.6% and 52% of strains at the concentrations of 0.05 µg/mL and 1 µg/mL, respectively. The MBEC values up to 0.4 µg/mL demonstrated that dalbavancin was active against most strains in pre-established adhered cells and 24 h old biofilms. The current results show that dalbavancin is active against adhered cells and biofilms in vitro, suggesting that this antimicrobial agent may be an option for the treatment of bone infections caused by MRSA.

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

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.