Antibiotic-Loaded Synthetic Calcium Sulfate Beads for Prevention of Bacterial Colonization and Biofilm Formation in Periprosthetic Infections

Abstract

e Periprosthetic infection (PI) causes significant morbidity and mortality after fixation and joint arthroplasty and has been extensively linked to the formation of bacterial biofilms. Poly(methyl methacrylate) (PMMA), as a cement or as beads, is commonly used for antibiotic release to the site of infection but displays variable elution kinetics and also represents a potential nidus for infection, therefore requiring surgical removal once antibiotics have eluted. Absorbable cements have shown improved elution of a wider range of antibiotics and, crucially, complete biodegradation, but limited data exist as to their antimicrobial and antibiofilm efficacy. Synthetic calcium sulfate beads loaded with tobramycin, vancomycin, or vancomycin-tobramycin dual treatment (in a 1:0.24 [wt/wt] ratio) were assessed for their abilities to eradicate planktonic methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis relative to that of PMMA beads. The ability of the calcium sulfate beads to prevent biofilm formation over multiple days and to eradicate preformed biofilms was studied using a combination of viable cell counts, confocal microscopy, and scanning electron microscopy of the bead surface. Biofilm bacteria displayed a greater tolerance to the antibiotics than their planktonic counterparts. Antibiotic-loaded beads were able to kill planktonic cultures of 10 6 CFU/ml, prevent bacterial colonization, and significantly reduce biofilm formation over multiple days. However, established biofilms were harder to eradicate. These data further demonstrate the difficulty in clearing established biofilms; therefore, early preventive measures are key to reducing the risk of PI. Synthetic calcium sulfate loaded with antibiotics has the potential to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material and, thus, to reduce the rates of periprosthetic infection. P eriprosthetic infection (PI) is a serious complication of total joint arthroplasty with high rates of associated morbidity (1, 2), and a growing body of data suggests that bacterial biofilms are the underlying cause (3-9). Within a biofilm, bacteria display a Ն1,000-fold tolerance to antibiotics than their planktonic counterparts (10) and significant resistance to innate and adaptive host immunity (11). Moreover, biofilms associated with orthopedic hardware are typically difficult to culture using conventional clinical microbiological methods, and the lack of a definitive diagnosis may result in an underestimate of infection rates (12, 13). Consequently, the underlying infection is difficult to diagnose and treat (6, 7), and often the only effective intervention is the twin strategy of thorough debridement and prostheses removal (14).Existing prevention strategies include the use of antibiotic-loaded poly(methyl methacrylate) (PMMA) cement spacers or beads to elevate local antibiotic levels at the surgical site. Studies have demonstrated a significant reduction in infection rates using antibiotic-impregnated ce...

Increased rates of genomic mutation in a biofilm co-culture model of Pseudomonas aeruginosa and Staphylococcus aureus

“…12 , was determined for mono-and co-culture biofilms of P. aeruginosa 183 PA21 and S. aureus UAMS-1 using a method adapted from Howlin et al (2015) 13 . 184…”

Synergistic effects of heat and antibiotics on Pseudomonas aeruginosa biofilms

“…The transport limitations mentioned above are due largely to the EPS surrounding the bacteria and limiting the transport of antibiotics to the bacterial cells (Anderl et al 2003; Walters III et al 2003). This slower transport of antibiotics can result in concentrations below the minimum inhibition concentration, which not only fail to eradicate the biofilm, but have also been shown to increase the likelihood of evolutionary resistance to that antibiotic in the biofilm (Gbejuade et al 2015; Howlin et al 2015). Another consequence of EPS transport limitation is the nutrient gradient in the biofilm and the resulting variation in metabolic activity among the bacteria.…”

Possibility of one-stage surgery to reconstruct bone defects using the modified Masquelet technique with degradable calcium sulfate as a cement spacer: A case report and hypothesis

“…Of note, radical debridement of the bone and surrounding soft tissues is the premise of the following surgical procedures. iii) With regards to the definitive outcomes of the combination of calcium sulfate with additives in reconstruction of bone defects, Howlin et al (18) identified that calcium sulfate with antibiotics may have a potential ability to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material, thus reducing the rates of periprosthetic infection. Following the comparison of PMMA with calcium sulfate as antibiotic carriers at the infected sites, McConoughey et al (13) indicated that calcium sulfate led to similar or improved outcomes compared to PMMA in the inhibition of bacterial growth.…”