Admixing Antimicrobials to PMMA Bone Cement in the Treatment of Bone and Joint Infections: The Development of Best Practice Recommendations

Aim Commercially available bone cement products with pre-mixed antimicrobials are available but do not cover all the organisms encountered (e.g. multi-drug resistant Gram-negatives and CoNS,VRE, fungi and NTM). Therefore, the manual mixing of additional antimicrobials when preparing the bone cement intraoperatively may be required to deliver localised high-concentrations of antimicrobial to treat resistant-organisms. These extemporaneous preparations have not been rigorously evaluated in experimental studies or clinical trials and do not follow strict regulatory approval processes. This project aims to establish best practice recommendations for safely compounding extemporaneously prepared antimicrobial-loaded polymethylmethacrylate (PMMA) bone cement in the theatre environment. From this, drug monographs for clinically useful antimicrobials will be prepared to guide practice.

Methods A systematic search was undertaken using EMBASE and PUBMED for all clinically relevant human and in-vitro experimental studies evaluating the addition of antimicrobials to PMMA bone cement in orthopaedic surgery (1975 through to March 2023). Data were extracted regarding clinical situations, formulation (including the antimicrobial choice and the amount to add), base cement, and preferred manual mixing technique. Clinical outcomes analysed included reoperation rates and systemic toxicity. Experimental outcomes of interest included antimicrobial elution and its effect on mechanical properties. Depending on the study type, PMMA intervention, surgery type and outcome, the studies were split according to primaries and revision.

Results We identified 1145 studies, of which 415 were excluded as out of scope. Seven hundred thirty studies were included; 377 relevant clinical studies, 197 in vitro studies and 156 reviews. Of the clinical studies, 6 RCTs, 116 non-comparative studies, 30 comparative cohort studies, 50 in-vivo elution studies, 79 case series and 96 case reports. Most clinical studies were uncontrolled and used various time points to evaluate outcomes. Most studies incorporated vancomycin and aminoglycosides into PMMA. Full-text reviews of clinical studies are required to assess the consistency of PMMA intervention within the study, follow-up period; antimicrobials admixed, the formulation used, antibiotic loading , total mass, and mixing technique .

Conclusion The literature reviewed do not adequately support recommendations on adding antimicrobials to PMMA or the amount to load. Ongoing review aims to establish pragmatic recommendations for clinicians and the development of individual drug monographs.