Variability in the release of antibiotics from PMMA bone cement spacers

The antibiotic-loaded PMMA spacers are being used with increased frequency in two-stage revision arthroplasty. The release of aminoglycosides and vancomycin, the most commonly used antibiotics, is prompt and concentrations are inhibitory. The release kinetic from PMMA bone cement shows a biphasic (bimodal) profile, consisting in an initial high rapid drug release followed by a slower but sustained phase. However, this common (general) profile of drug release kinetics from PMMA spacers in vitro may present (exhibits) great variability in terms of drug amount, modality, and duration of elution. Initial drug concentration, cement surface area and porosity are essential and well-known factors in determining the drug release. Moreover, viscosity, vacuum preparation and the different technical characteristics of commercially available spacers are additional factors of variability. Industrial preformed spacers are considered superior to hand- and/or mold-made devices because of uniform mixing and standardized procedures Spacers produced by different manufacturers vary in their mechanical properties and antibiotic elution characteristics. Small changes in the formulation of a bone cement can further (also) affect these properties. Similar bone cements produced by various brands release different amount of drugs. Gentamicin diffuses from Palacos in larger amount and for longer period than from Simplex e CMV. Spacers produced in France (Synicem, Gentamicin 5%) and in Argentina (Subiton, Gentamicin 5%) eluted less total gentamicin than those produced in Italy (Spacer G, Gentamicin 1.9%) and showed a delayed peak drug release. The low initial release of antibiotic can contribute to unsatisfactory antimicrobial effect and to risk of selection of resistant bacteria. Some spacers release gentamicin for longtime (months) while others release antibiotic for only two weeks. In the last years an evolution in PMMA spacers production occurred and modifications in the polimerization process of cement can increase cement porosity and antibiotic elution from spacer. The current commercial preformed spacers (Spacer G, prepared with Cemex HP) release more gentamicin (34.1 mg) than previous models prepared with Cemex SP (16.4 mg) for 10 days elution and maintain high elution rate (1.4-1.6 mg/day after one month). The combination of Gentamicin and Vancomycin maintains an elution pharmacokinetic profile superimposable to that of Gentamicin and Vancomycin alone, with synergistic effects against multiresistant bacteria at prosthetic infection site. In conclusion, the antibiotic release from PMMA spacers of different (various) brands is not equivalent. The old elution data are no longer valid for new preparations. Consequently, this additional factor of variability should be considered in the clinical practice and literature data revision.