Antibiotic PMMA Research Articles

Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for Postimplantation Refilling.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination antibiotic PMMA composite system composed of rifampicin-filled β-cyclodextrin (β-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through zone of inhibition, drug activity, antibiotic release, and refilling, as well as mechanical studies. Our combination antibiotic PMMA composite system achieved up to an 8-fold increase in the duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for load-bearing applications (e.g., bone cement), our composites are certainly amenable for a variety of nonload-bearing applications (e.g., antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).

Successful management of intramedullary nail associated infection with reaming and antibiotic cement beads/rod

Objective To assess the efficacy of using reaming and antibiotic cement beads/rod for intramedullary nail as-sociated infection. Methods Data of 12 patients with intramedullary infection of tibia or femur following intramedullary nailing from October 2014 to April 2016 were retrospectively analyzed. There were 10 men and 2 women aged from 19 to 63 years old with an average age of 39.2 years. In 5 cases the disease was localized in the femur with one case of nonunion, and in other 7 cases the disease was localizedin the tibia with two cases of nonunion. The initial injury included closed fracture in 8 patients and open fracture in 4 patients which were all Gustilo-AndersonⅡ. According to the Cierny-Mader classification of adult osteomyelitis, 6 cases were typeⅠ (medullary osteomyelitis), 4 cases were type Ⅰcombined with type Ⅲ (medullary and localized osteomyelitis), and 2 cases were typeⅠ combined with type Ⅳ (medullary and diffuse osteomyelitis). Surgical technique included removal of the intramedullary nailand reaming and irrigation of the medullary canal to remove intramedullary debris. The drainage sinus and soft tissues abscess were excised if existed. An local or enbloc resection for the infected or necrotic bone was performed if there was lo-cal or diffuse infection in the fracture sites. Ilizarov technique was performed for segment bone defect. The bone union was ob-served in nine patients and stable nonunion in one. Antibiotic PMMA beads were inserted into intramedullary canal for these ten cases after debridement, and the antibiotic beads were removed approximately 12-14 days after implantation. The antibiotic ce-ment rod was inserted into the medullary canal to provide stabilization in the other 2 cases. All the patients received intravenous antibiotics systemically for three weeks, and followed by three weeks of oral antibiotics. Results At a mean follow-up period of 23.5 months (range, 15-33 months), no recurrence of infection was observed. There were 3 cases of nonunions. One case of tibial nonunion had been achieved union 10 months after insertion of an antibiotic cement rod. One with stable nonunion of tibia was treated with antibiotic PMMA beads, and enbloc resection for the infected bone was performed after the extension of infection had been narrowed at the nonunion. 6 cm of bone defect was treated with bone transport and then union was obtained 16 months after operation. The third case was infected nonunion in the femur with 4 cm bone defect after debridement. The femur was shortened and temporarily stabilized with the intramedullary antibiotic cement rod. The rod was removed three months after the operation, and then the femur was lengthened. The docking site and the regeneration area were healed 12 months after the lengthening opera-tion. Conclusion The clinical results shows that reaming and antibiotic cement beads/rod appears an effective and safe alterna-tive for management of intramedullary nail associated infection of the tibia and femur. Key words: Femur; Tibia; Infection; Fracture fixation, intramedullary

Viable bacteria persist on antibiotic spacers following two-stage revision for periprosthetic joint infection.

Treatment in periprosthetic joint infection (PJI) remains challenging. The failure rate of two-stage revision and irrigation and debridement with component retention in PJI suggests that biofilm cells have a high tolerance to antibiotic chemotherapy. Previous work has demonstrated that biofilm cells have high antibiotic tolerance in vitro, but there is little clinical evidence to support these observations. The aim of this study was to determine if retrieved antibiotic spacers from two-stage revision total knee arthroplasty for PJI have evidence of remaining viable bacteria. Antibiotic poly (methyl methacrylate) (PMMA) spacers from two-stage revision total knee arthroplasty for PJI were prospectively collected and analyzed for bacterial 16s rRNA using polymerase chain reaction (PCR), reverse transcription (RT)-PCR, quantitative RT-PCR (qRT-PCR), and single genome analysis (SGA). PCR and RT-PCR identified bacterial species on 53.8% (7/13) of these samples. When initial culture negative cases are excluded, 68% (6/9) samples were identified with bacterial species. A more rigorous qRT-PCR analysis showed a strong positive signal for bacterial contamination in 30.7% (4/13) of cases. These patients did not show any clinical evidence of PJI recurrence after 15 months of follow-up. Because the half-life of bacterial rRNA is approximately a few days, the identification of bacteria rRNA on antibiotic PMMA spacers suggests that viable bacteria were present after conclusion of antibiotic therapy. This study provides evidence for the high tolerance of biofilm cells to antibiotics in vivo and the important role of bacterial persisters in PJI. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:452-458, 2018.

An Important Backdrop to the Continued Discussion on the Use of Antibiotic-Containing Bone Cements

The use of antibiotic-containing polymethylmethacrylate, or antibiotic PMMA, in revision of a total hip or total knee replacement due to a previous infection is currently accepted practice. Additionally, despite lack of regulatory approval in the United States, the “off-label” use of antibiotic PMMA for primary arthroplasty by orthopaedic surgeons is substantial and has continued to increase. The widespread use of antibiotic PMMA in total joint replacement provides ample clinical relevance to the article by Meyer et al. regarding the effects of vacuum-mixing on six widely used antibiotic PMMA formulations. One of the strengths of the work is the logical study design. The authors utilize a previously reported methodology for creating pellets of uniform consistency with virtually identical geometry1. Thirty pellets of each antibiotic (fifteen vacuum-mixed and fifteen atmospheric) were evaluated each day during a five-day elution protocol and were compared between groups as …

Premixed Antibiotic Bone Cement: An In Vitro Comparison of Antimicrobial Efficacy

After Food and Drug Administration (FDA) approval of premixed antibiotic bone cements (polymethylmethacrylate [PMMA]), these products are being used with increasing frequency during revision and primary hip and knee arthroplasties. To date, no studies have compared the antimicrobial efficacy of more than 2 products directly. Using a 7-day modified Kirby-Bauer assay, we assessed the in vitro antibacterial properties of 5 FDA-approved, commercially available antibiotic PMMAs. Significant differences in antimicrobial activity were noted among the antibiotic PMMA products included in this investigation. Antibacterial activity of all products tested was greatest on day 1 and rapidly diminished thereafter. Results of this investigation suggest that the antibacterial efficacies of premixed antibiotic PMMA products are not equivalent.

Antimicrobial Efficacy of Five Commercially Available Antibiotic Bone Cements: An In Vitro Comparison

Antibiotic bone cement (PMMA) can be used for primary total knee arthroplasty/total hip arthroplasty infection prophylaxis as well as treatment and reconstruction of septic total knee arthroplasty/total hip arthroplasty. To date, no investigation has compared antimicrobial efficacies of commercially available, “pre-mixed” antibiotic PMMAs. This study compares the in vitro antibacterial activity of 5 antibiotic PMMA formulations.

The Effect of Glycine Filler on the Elution Rate of Gentamicin from Acrylic Bone Cement

Elution of antibiotics from acrylic bone cement (polymethylmethacrylate [PMMA]) is dependent on the access of fluid to the depths of the cement that contains the antibiotic. Commercially prepared antibiotic beads that are porous have higher elution rates than hand-mixed, nonporous antibiotic PMMA mixtures. To increase the elution of gentamicin from hand-mixed PMMA, glycine was added as a filler to produce porosity. Elution of gentamicin from the antibiotic PMMA-glycine mixture increased with increasing amounts of glycine. With 3.6 g gentamicin powder and 14 g of crystalline glycine per batch of Palacos PMMA, the elution of gentamicin from the PMMA at 2 days was, similar to the previously documented elution of gentamicin from commercially prepared porous Septopal PMMA beads. With further investigation it may be possible to identify a specific filler and a volume of filler that can be hand mixed in antibiotic PMMA to produce the elution behavior that is needed for specific clinical requirements.