Mixing Method Affects Elution and Strength of High-dose ALBC: A Pilot Study

Abstract

Background High-dose antimicrobial-loaded bone cement (ALBC) is used to treat orthopaedic infections. High-dose ALBC is not commercially available and requires surgeon directed formulation, and there are several different methods used to mix high-dose ALBC. Questions/purposes We asked whether the mixing method affected antimicrobial elution and mechanical properties of high-dose ALBC. Methods ALBC was formulated with Simplex 1 P bone cement and 10 g of vancomycin per batch using one of three mixing methods: (1) hand-stirred using a standard bowl and spatula, (2) bowl-mixed using a mechanical mixing bowl, and (3) dough-phase mixing where the vancomycin was left in chunks (1-5 mm) and folded into the cement during the dough phase after adding the monomer. We eluted 45 standardized test cylinders (15 per mixing technique) for 30 days under infinite sink conditions. We tested 135 (45 per mixing method) similarly eluted cylinders in axial compression to failure. Results Dough-phase mixing lead to greater antimicrobial delivery, but lower compressive strength than the handstirred or bowl-mixed methods. Dough-phase cement released 18,570 lg of vancomycin versus 11,731 for handstirred and 7700 lg for bowl mixed. Compressive strength for dough-phase mixing after 30 days of elution was 36 MPa, while both hand-stirred and bowl mixed cements were 56 MPa. Conclusions Performance of high-dose ALBC was affected by mixing method. Dough-phase mixing led to greater antimicrobial delivery, but caused greater loss in compressive strength.

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

“…This large decrease in compressive strength is likely related to the very large volume fraction of 24 vol%. The loss of compressive strength caused by the 300-mg formulation was consistent with previous studies of highdose ALBA with similar volume fractions after 1 day in elution (78-52 MPa for 300 mg voriconazole, 95-59 MPa for 10 g vancomycin) [13]. The average compressive strength of Simplex P without antimicrobial is approximately 85 MPa under identical experimental conditions.…”

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

“…The higher-dose formulation released more gentamicin over a longer duration. Release from the higher-dose G-PNDJ formulation is very similar to the release characteristics of high-dose antimicrobial-loaded bone cement over the first week [41] but G-PNDJ does not have the long-duration subtherapeutic release that occurs with antimicrobial-loaded bone cement because it is fully degraded by 4 weeks [50]. It is generally accepted that high-dose antimicrobial-loaded bone cement is indicated for treatment of established infection.…”

Antimicrobial Distribution From Local Delivery Depends on Dose

“…We know that the amount of antimicrobial (or Gd-DTPA) released from cement is affected both by the amount of drug loaded [21,22] and the porosity of the cement [23]. McLaren et al [21] showed relatively similar elution from all of the commercially available ''low-dose'' formulations, although the current study only evaluated Simplex 1 .…”