Antibiotic-loaded bone cement is the most widely used approach for the treatment of biofilm-induced septic sequelae in orthopedic surgery. Dalbavancin is a lipoglycopeptide that acts against Gram-positive bacteria and has a long half-life, so we aimed to assess whether it could be a new alternative drug in antibiotic-loaded bone cement for the treatment of periprosthetic joint infections. We assessed the elution capacity of dalbavancin and compared it with that of vancomycin in bone cement. Palacos^®R (Heraeus Medical GmbH, Wehrheim, Germany) bone cement was manually mixed with each of the antibiotics studied at 2.5% and 5%. Three cylinders were obtained from each of the mixtures; these were weighed and incubated in 5 mL phosphate-buffered saline at 37°C under shaking for 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 168 h, and 336 h. PBS was replenished at each time point. The samples were analyzed using high-performance liquid chromatography (vancomycin) and mass cytometry (dalbavancin). Elution was higher than the minimum inhibitory concentration (MIC)90 for both antibiotics after 14 days of study. The release of vancomycin at 14 days was higher than of dalbavancin at each concentration tested (p = 0.05, both). However, the cumulative release of 5% dalbavancin was similar to that of 2.5% vancomycin (p = 0.513). The elution capacity of dalbavancin reached a cumulative concentration similar to that of vancomycin. Moreover, considering that the MIC90 of dalbavancin is one third that of vancomycin (0.06 mg/L and 2 mg/L, respectively) and given the long half-life of dalbavancin, it may be a new alternative for the treatment of biofilm-related periprosthetic infections when loaded in bone cement.

As we previously demonstrated that tranexamic acid (TXA), an antifibrinolytic, showed an antibacterial effect alone and in combination with vancomycin and gentamicin, we now wanted to analyze its own efficacy using new, different fluorescent staining reagents that target different components of the biofilm matrix and compare which one quantifies biofilm reduction better. A 10⁸ cfu/mL suspension of the Staphylococcus aureus (ATCC29213) strain was placed into the wells of a 24-multiwell plate covered with glass slides coated with 10% poly-L-lysine under agitation for 24 h at 37 °C. After 3 washes with PBS, wells were treated with either TXA 10 mg/mL or sterile water and incubated for 24 h at 37 °C. After three washes with PBS, the density area of the following biofilm components was calculated using confocal laser scanning microscopy: extracellular proteins (Sypro Ruby), α-extracellular polysaccharides (ConA-Alexa fluor 633), α or β-extracellular polysaccharides (GS-II-Alexa fluor 488), bacterial DNA (PI), and eDNA (TOTO^®-1). We observed a statistically significant reduction in the occupied area by all components of the S. aureus biofilm (p < 0.001) after TXA 10 mg/mL treatment, compared to the positive control. All biofilm components’ reduction percentages reached ≥90.0%. We demonstrated that TXA reduced both bacteria and extracellular matrix components of S. aureus biofilm by using five different stain reagents, with all being equally valid for quantification.

Despite the measures employed, fracture-related infections remain a concern after fracture fixation worldwide. Recently, the role of tranexamic acid as a protective drug against postsurgical infections in joint replacement and orthopedic trauma surgery has been proposed, where tranexamic acid has been associated with less surgical wounds complications and infectious complications including periprosthetic joint infection. The mechanism through which tranexamic acid exerts a protective effect against peri-implant infection is still the subject of debate. Although some authors hypothesize an indirect effect inhibiting the formation of postoperative hematoma, there are several studies that show a direct antibacterial effect of the drug against the capacity of bacterial aggregation, even avoiding biofilm formation, favoring the immune response of the host and the action of antibiotics. The purpose of this narrative review is to show the current role of tranexamic acid in orthopedic trauma, specifically its relationship with the prevention of infections related to implants.

Based on previous studies of our group in which we demonstrated that dalbavancin loaded in bone cement had good elution capacity for the treatment of biofilm-related periprosthetic infections, we now assess the anti-biofilm activity of dalbavancin and compare it with that of vancomycin up to a 3-month period. We performed an in vitro model based on calculation of percentage reduction of log cfu/ml counts of sonicated steel discs contaminated with Staphylococci and further exposed to bone cement discs loaded with 2.5% or 5% vancomycin and dalbavancin at each study period (24 hours, 48 hours, 1 week, 2 weeks, 6 weeks, 3 months). In addition, we tested the anti-biofilm activity of eluted vancomycin and dalbavancin at each study period based on a 96-well plate model assessing percentage reduction of metabolic activity. Overall, dalbavancin showed a significant concentration decrease from 2 weeks of incubation and maintain its anti-biofilm activity up to 3 months, whereas, despite vancomycin showed a significant decrease at 1w and then it gradually increased, its anti-biofilm activity was significantly lower. Dalbavancin percentage reduction cfu/ml counts were higher than those of vancomycin, both at 2.5% and 5% concentrations. Reduction of log cfu/ml counts were higher for S. epidermidis than for S. aureus, being more notable for 5% dalbavancin at month 3. In addition, percentage reduction of metabolic activity also decreased at 3 months in 5% dalbavancin and 5% vancomycin, being more notable in the last.