A meta-analysis of bone cement mediated antibiotic release: Overkill, but a viable approach to eradicate osteomyelitis and other infections tied to open procedures

Highlights: • ALBCs release antibiotic as a small but clinically effective burst dose. • More loading is linked with higher dose and weaker cement strength. • Future antibiotic release systems will use both diffusion and burst release schemes. A number of clinical studies have highlighted the success of antibiotics formulated at concentrations between 0 and 6% w/w into bone cements to address localized infections. Separately, some commercial manufacturers have produced gentamycin-infused bone cement mixtures as a countermeasure to infection. The anecdotal evidence suggests that antibiotic infused cements can help eradicate or delay the onset of infections. Quantifying the functionality of that response is more challenging. We have surveyed the literature to identify studies in which controlled drug release or mechanical behavioral assessments have been conducted on drug-infused cements. The focus here is on vancomycin (VAN) in part due to its higher potency relative to gentamycin and its more common usage for staph infections. Takeaways from the limited pool of research studies indicate that large fractions (>99%) of the infused vancomycin remain sequestered in the cement and aren't bioavailable after solidification. Antibiotic fluence ranged from 1 to 283 μg/cm²hr. The initial strength of the various antibiotic loaded samples as produced were 52–96 MPa. Simulated exposures in a fluid environment by submersion reduced the antibiotic loaded strengths between 3 and 29%. Some strength measurements were noted below the ASTM F451 standard for acrylic bone cement although drug releasing spacers likely have different requirements. The glassy behavior of the cured cement led to both vancomycin and gentamicin having low permeability and a burst response. Smaller drug molecules and more gel-like immobilization matrices with lower glass transition temperatures offer higher potential for larger and more comprehensive drug bioavailability.