33. IN VITRO ACTIVITY OF FUSIDIC ACID AND VANCOMYCIN IN PMMA BONE CEMENT FOR THE TREATMENT OF METHICILLIN-RESISTANT STAPHLYOCOCCUS AUREUS

Abstract

Purpose: This study investigates the synergistic use of fusidic acid with vancomycin, and linezolid in poly-methylmethacrylate (PMMA) cement for the treatment of orthopedic MRSA and MRSE infections. Alone, Vancomycin is typically eluted in limited quantities from cement. The purpose of this study was to

1. combine FA and Vancomycin, and Linezolid alone in PMMA cement and characterize antibiotic elution, and

2. to improve drug release using polyethylene glycol (PEG) and NaCl in PMMA cement.

Method: Standardized 1g pellets of Palacos cement were manufactured containing Vancomycin and FA or Linezolid at increasing concentrations in three batches: without additive, with increasing concentrations of PEG, and with increasing concentrations of NaCl. The pellets were incubated in phosphate buffered saline and sampled at regular intervals. Drug analysis was performed with high pressure liquid chromatograpy.

Results: Total drug release at 2.5% loading of Vancomycin alone was 0.84% and of FA was 2.35%. Linezolid showed comparable release profiles. Vancomycin and FA combined yeilded Vancomycin release of 6.2% and FA of 8.4%. The addition of 30% PEG increased release of Vancomycin and Fusidic Acid by six-fold. The addition of 18% NaCl increased total Vancomycin release by 11-fold but had no effect on FA release.

Conclusion: Linezolid, Vancomycin and FA can be combined in PMMA and have favorable release profiles. The addition of PEG and NaCl dramatically increases the release of antibiotics, with the exception of FA and NaCl. These strategies may be useful in the management of MRSA/MRSE infections.