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.

AIM: Chronic osteomyelitis is a difficult to treat infection requiring prolonged antimicrobial therapy and involving systems of local antimicrobial delivery. Linezolid is a new antimicrobial agent with well documented in vitro activity against gram positive cocci when resistance to other antistaphylococcal agents is present. Few data are present regarding its embedding in local antimicrobial delivery systems and subsequent elution. The elution of linezolid by a polylactic acid (PLA) system was studied.

METHODS: Linezolid was dry-mixed with PLA at a ratio of 1:9, ie 50mg of linezolid were mixed with 450mg PLA. The mixture was diluted with 0,5mL of methanol and placed at the bottom of a cylindrical vial. Two replicas were created and one mL of Mueller-Hinton broth was added over the free solid surface of each mixture. Vials were transferred to a 37°C incubator and broth was replaced every 48h for 11 days. Concentration of linezolid was determined by an HPLC method using a Zorbax Eclipse XDB-C8 column and UV detection.

RESULTS: Mean linezolid concentration at days 1, 3, 5, 7, 9 and 11 was 2778.54 mg/L, 2456.22 mg/L, 668.63 mg/L, 324.86 mg/L, 390.10 mg/L, and 155.28 mg/L respectively.

CONCLUSION: Elution of linezolid by a PLA local delivery system remains very high throughout the period studied. The results are promising for the therapy of staphylococcal chronic osteomyelitis with the use of a PLA local antimicrobial delivery system employing linezolid.