Antimicrobial properties and elution kinetics of linezolid-loaded hip spacers in vitro

Abstract

Bacterial adhesion to and -persistence on antibiotic-loaded bone cement is an increasing problem. New antibiotics with good antimicrobial and pharmacokinetic properties (e.g. linezolid) may be the solution to this problem; however, few data concerning linezolid-loaded acrylic cement are currently available. Ten gentamicin-linezolid-loaded hip spacers (1 g gentamicin/2.4 g linezolid/80 g PMMA; five spacers including a metallic endoskeleton, five with no metallic components) were tested in vitro against a strain of methicillin-resistant Staphylococcus aureus with regard to antibiotic release and bacteria growth inhibition. Daily, the antibiotic elution was determined by high liquid performance chromatography (linezolid) and fluorescence polarization immunoassay (gentamicin), the bacteria growth inhibition photometrically at 546 nm. All spacers demonstrated growth inhibition for 8 days. Peak average concentrations were reached for both agents on day 1 (gentamicin-35.10 mug/mL [24.10-52.52], linezolid-36.28 mug/mL [22.87-71.76]). After 8 days, 0.97% [0.93-1.05%] of the initial amount of linezolid and 3.13% [2.85-3.31%] of gentamicin were meanly released from spacers containing a metallic endoskeleton. In those containing of simple cement these values were 1.22% [0.91-1.59%] and 2.67% [2.12-2.73%], respectively. Linezolid demonstrated acceptable elution kinetics from bone cement; however, further experimental research and animal studies should clarify any possible side effect of linezolid-loaded cement media before definitive use in the clinical practice.