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EXPERIMENTAL MRSA OSTEOMYELITIS TREATMENT BY A BIODEGRADABLE POLYLACTIDE SYSTEM RELEASING LINEZOLID



Abstract

Introduction: Biodegradable systems releasing antibiotics are promising candidates for the management of chronic osteomyelitis. Gentamicin and fluoroquinolones are the commonest antibiotics applied with these systems. The effectiveness of a new system from polymerized dilactide (PLA) with incorporated linezolid has been investigated in a rabbit model for treating osteomyelitis by methicillin-resistant Staphylococcus Aureus (MRSA).

Methods: The PLA – Linezolid system was made after thorough stirring 2gr of polymer with 100 mg of linezolid. Experimental osteomyelitis was established in 40 rabbits by a modification of the Norden model. Methicillin-resistant Staphylococcus aureus (MRSA) was applied as the test isolate. After drilling a hole in the upper right femur, the isolate was inoculated along with a thin needle working as a foreign body. After three weeks the needle was removed and cultured and PLA-Linezolid system was implanted in half of the animals. Animals were sacrificed at regular time intervals and tissue around the site of implantation was sent for histologic examination and quantitative cultures.

Results: At 2 – 4 – 6 – 8 – 10 weeks time after removal of the needle results (mean values) were as follows (Controls/PLA-Linezolid): Log10 (cfu/g) at infection site: 2.99/5.68 – 3.44/3.20 – 3.22/2.39 – 1.00/1.27 – 1.00/1.00 respectively and Δlog10 (cfu/g) compared to start: −0.05/−3.23 – 0.23/0.13 – 0.05/0.93 – 1.34/1.09 – 3.31/3.34 respectively. Histology confirmed the previous mentioned results, showing an early decrease following by late recurrence of the infectious reaction at the animals that PLA-Linezolid system was used.

Conclusions: It is concluded that the applied system achieved an early decrease of the tissue bacterial load which was not maintained until late on follow-up. This might be explained by the bacteriostatic mode of action of linezolid.

Correspondence should be addressed to: EFORT Central Office, Technoparkstrasse 1, CH – 8005 Zürich, Switzerland. Email: office@efort.org