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

Staphylococcus aureus, 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 Staphylococcus aureus (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 bone marrow (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 marrow and bone, respectively. CDA loaded with linezolid enhance the efficacy of the IV linezolid regimen by more than one log(10)CFU/g.

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

AIMS: To assess the impact of antibiotic therapy on severe osseous infections, animal models of chronic bacterial infections have been developed; however, these models suffer from many experimental limitations. The aim of this work was to develop a new model system in which high levels of bacteria are obtained within femoral bone marrow and bone tissue, and such infections are maintained for at least 14 days. METHODS AND RESULTS: Experimental osteomyelitis was induced in 25 New Zealand white rabbits. A 10(9) CFU ml(-1) suspension of methicillin-resistant Staphylococcus aureus was injected into the knee after bone trepanation. On day 3, surgical debridement was performed to mimic a surgical procedure. Animals were euthanized 1, 2, 3, 9 and 14 days post-inoculation to determine the bacterial counts in marrow and bone, and to evaluate the stability of the infection. Inoculated lesions also were assessed for changes in histological parameters on days 3 and 7 post-inoculation. At days 1, 2, 3, 9 and 14 post-inoculation, we observed 6·50 ± 0·64, 7·30 ± 0·49, 7·82 ± 0·19, 8·00 ± 1·48 and 8·99 ± 0·20 log10 CFU g(-1) in bone marrow and 8·40 ± 0·68, 7·65 ± 0·27, 7·58 ± 0·30, 8·88 ± 0·52 and 8·28 ± 0·39 log10 CFU g(-1) in bone tissue, respectively. No statistical differences in bacterial count were found between bone marrow and bone tissue at any time point. CONCLUSION: This new model of acute osteomyelitis was validated by histological and microbiological changes in the absence of sclerosing agents, and these changes remained stable for 14 days. SIGNIFICANCE AND IMPACT OF THE STUDY: These results describe a new experimental model of acute osteomyelitis and demonstrate its usefulness in assessing the activity of antibacterial agents in vivo soon after bone infection.

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

Daptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (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 S. aureus from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage.

In vivo assessment of the antimicrobial activity of a calcium-deficient apatite vancomycin drug delivery system in a methicillin-resistant Staphylococcus aureus rabbit osteomyelitis experimental model.

The antimicrobial activities of calcium-deficient apatite loaded with different concentrations (25, 100, and 500 microg/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.

An epidemiological survey of human listeriosis in France during 1987, using serotyping and phage typing.

During 1987 the French National Reference Center for Listeria received, from this country, 384 Listeria monocytogenes strains isolated from human listeriosis cases. A constant exchange of information and strains between the Reference Center and the Bacterial Ecology Unit of the Institute Pasteur of Paris allowed complete characterization of these isolates, using serotyping and phage typing. Among the strains studied 22%, 13% and 63%, respectively belonged to serovars 1/2a, 1/2b, and 4b, but this distribution can vary according to place, and time of isolation. Only 58% of strains were phage-typeable (1/2a: 29%), (1/2b: 66%) and (4b: 40%). Phage typing allows to consider that French human cases, in 1987, were mainly sporadic. However, a small number of cases corresponding to similar phage types could be clustered according to place and/or time.