Introduction: Bacterial biofilms are an important
virulence factor in chronic periprosthetic joint
infection (PJI) and other orthopedic
infection since they are highly tolerant to
antibiotics and host immunity.
Antibiotics are mixed into carriers such as
bone cement and
calcium sulfate bone void fillers to achieve sustained high concentrations of
antibiotics required to more effectively manage biofilm
infections through local release. The effect of
antibiotic diffusion from
antibiotic-loaded
calcium sulfate beads (ALCS-B) in combination with
PMMA bone cement spacers on the spread and killing of Pseudomonas aeruginosa Xen41 (PA-Xen41) biofilm was investigated using a "large
agar plate" model scaled for clinical relevance. Methods: Bioluminescent PA-Xen41 biofilms grown on discs of various orthopedic materials were placed within a large
agar plate containing a
PMMA full-size mock "spacer" unloaded or loaded with
vancomycin and
tobramycin, with or without ALCS-B. The amount of biofilm spread and log reduction on discs at varying distances from the spacer was assessed by bioluminescent imaging and viable cell counts. Results: For the unloaded spacer control, PA-Xen41 spread from the biofilm to cover the entire plate. The loaded spacer generated a 3 cm zone of inhibition and significantly reduced biofilm bacteria on the discs immediately adjacent to the spacer but low or zero reductions on those further away. The combination of ALCS-B and a loaded
PMMA spacer greatly reduced bacterial spread and resulted in significantly greater biofilm reductions on discs at all distances from the spacer. Discussion: The addition of ALCS-B to an
antibiotic-loaded spacer mimic increased the area of
antibiotic coverage and efficacy against biofilm, suggesting that a combination of these depots may provide greater physical
antibiotic coverage and more effective dead space management, particularly in zones where the spread of
antibiotic is limited by diffusion (zones with little or no fluid motion).