Efficacy of daptomycin combined with rifampicin for the treatment of experimental meticillin-resistant (MRSA) acute osteomyelitis

International audienceDaptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant (MRSA). Daptomycin in combination with rifampicin needs to be assessed in bone infection. An MRSA acute osteomyelitis model was used. Daptomycin and vancomycin were compared, alone or in combination with rifampicin, over 4 days. Surviving bacteria were counted in bone, bone marrow and joint fluid. Vancomycin and daptomycin as single therapies were ineffective, but both combinations were significantly more effective than the corresponding monotherapy. Combination of daptomycin and rifampicin could prevent from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage

A new experimental model of acute osteomyelitis due to methicillin-resistant Staphylococcus aureus in rabbit

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Design and Characterisation of Multi-Gene Expression Vectors for CHO Cell Engineering

The antimicrobial activities of calcium-deficient apatite loaded with different concentrations (25, 100, and 500 mu g/mg) of vancomycin as a filling biomaterial were evaluated in a methicillin-resistant Staphylococcus aureus (MRSA) rabbit acute osteomyelitis model. Bacterial counts in bone, bone marrow, and joint fluid samples treated with forms of the apatite were compared to those in tissue samples receiving a constant intravenous vancomycin infusion after 4 days. This study demonstrates that using a calcium-deficient apatite loaded with vancomycin dramatically decreases the bacterial counts in bone and marrow

A delivery system of linezolid to enhance the MRSA osteomyelitis prognosis: in vivo experimental assessment

International audienceStaphylococcusaureus, a major responsible microorganism of osteomyelitis, represents a challenge to treat because of the poor penetration of antibiotics in bone and increasing minimum inhibitory concentrations (MICs) to glycopeptides. The calcium-deficient apatites (CDA), closer to the biological components found in bone and other calcified tissues, have osteoconductive properties. So, to process severe osseous infections, CDA can be used to deliver in the infectious site antibiotics like linezolid. The acute experimental osteomyelitis due to methicillin-resistant Staphylococcusaureus (MRSA) was induced in rabbit’s femurs and surgery mimicking human procedures was performed at day three after inoculation. Animals were randomly assigned to treatment groups: L(IV)[4-day linezolid IV infusion, human-equivalent dose of 10 mg/kg/12 h], L(CDA50%) (100 mg CDA with linezolid 500 μg/mg) and L (CDA50%) +L (IV). Surviving bacteria were counted in bonemarrow (BM) and bone (Bo) at day 3 (before treatment), day 7 (4-day treatment) or day 17 (14-day treatment). L(iv)was effective after a 4-day treatment with a log[10]CFU/g decrease of −2.63±1.92 and −2.17±1.58 in bone marrowand bone, respectively. CDA loaded with linezolid enhance the efficacy of the IV linezolid regimen by more than one log[10]CFU/g

New in vitro and in vivo models to evaluate antibiotic efficacy in Staphylococcus aureus prosthetic vascular graft infection

International audienceOBJECTIVE: Prosthetic vascular graft infection (PVGI) is an emerging disease, mostly caused by staphylococci, with limited data regarding efficacy of current antistaphylococcal agents. We aimed to assess the efficacy of different antibiotic regimens. METHODS: Six different strains of MSSA and MRSA were used. We compared results of minimal biofilm inhibitory and eradicating concentrations (MBICs and MBECs) obtained with a Calgary Biofilm Pin Lid Device (CBPD) with those yielded by an original Dacron(®)-related minimal inhibitory and eradicating concentration measure model. We then used a murine model of Staphylococcus aureus vascular prosthetic material infection to evaluate efficacy of different antibiotic regimens: vancomycin and daptomycin combined or not with rifampicin for MRSA and the same groups with cloxacillin and cloxacillin combined with rifampicin for MSSA. RESULTS: We demonstrated that classical measures of MBICs and MBECs obtained with a CPBD could overestimate the decrease in antibiotic susceptibility in material-related infections and that the nature of the support used might influence the measure of biofilm susceptibility, since results yielded by our Dacron(®)-related minimal eradicating assay were lower than those found with a plastic device. In our in vivo model, we showed that daptomycin was significantly more bactericidal than comparators for some strains of MRSA or MSSA but not for all. For the majority of strains, it was as efficient as comparators. The addition of rifampicin to daptomycin did not enhance daptomycin efficacy. CONCLUSIONS: Despite the heterogeneity of results according to bacterial strains, these innovative models represent an option to better evaluate the in vitro efficacy of antibiotics on Dacron(®)-related biofilm S. aureus infections, and to screen different antibiotic regimens in a mouse model of PVGIs