# Antibacterial Effect of Topically Administered Transcamic Acid in Large Joint Arthroplasty
## 4 Discussion  
With the objective of better understanding the local effects of topically administered TXA and its potential contribution to a reduction of early postoperative infections in arthroplasty, we designed an in vitro study aimed at evaluating its effect on clinically relevant bacterial strains. Presumed growth inhibitory and bactericidal effects of TXA were investigated using a microdilution technique and kinetic growth assay. None of the tested TXA concentrations had a bactericidal effect on any of the 22 tested bacterial strains, since bacteria reassumed growth after subculturing onto media without TXA. However, a growth inhibitory effect was shown on eight tested bacterial strains at higher TXA concentrations (50 and 100 mg/mL) with the microdilution technique. More specific TXA-induced dynamic changes in bacterial growth of all tested bacterial strains became evident during the kinetic growth assay. TXA is an antifibrinolytic drug used routinely in orthopedic surgery. It inhibits fibrinolysis by blocking the lysine binding site on plasminogen, competitively inhibiting the activation of plasminogen to plasmin [9]. Some studies have found that application of TXA can also decrease the incidence of periprosthetic joint infections. Based on the available literature, some of the beneficial effects in regard to postoperative infection rates can be attributed to the antifibrinolytic effect of TXA, since it has been shown significantly to lower the incidence of surgical wound hematomas [22], which in themselves predispose a wound to bacterial colonization. Additionally, it reduces the overall need for allogenic blood transfusions, which carry immunomodulatory properties and have been shown to increase the risk of infection after arthroplasty [6; 7; 33; 34]. While TXA is commonly used in surgical settings, particularly in orthopedic surgeries, only a few studies investigating its effects on bacteria and biofilm have been performed, showing mixed results. A recent study conducted in vitro by [PERSON] et al. [27] assessed the effect of TXA on bacterial growth of 6 _S. aureus_, 4 _S. epidermidis_, and 4 _C. acnes_ strains. They concluded that the percentage of reduction in bacterial growth was greater at lower TXA concentrations. However, this study only tested its effect at concentrations of 10 and 50 mg/mL, using endpoint measurements of bacterial counts, cell viability, and metabolic activity. In another study by [PERSON] et al. [28], they researched the possible synergistic effect of TXA combined with vancomycin or gentamicin. They reported a synergistic effect of TXA with antibiotics against staphylococcal strains, which was more pronounced at 10 mg/mL compared with 50 mg/mL of TXA. Our findings did not correlate with those shown in their studies. However, we performed kinetic growth assays that allowed for continuous monitoring of bacterial growth over time and growth curve examinations. Our results showed a dose-dependent growth inhibition observed at TXA concentrations equal to or  
Figure 5: Number of bacterial strains that showed a decrease in the maximum specific growth rate during incubation at different TXA concentrations compared with their respective reference controls. higher than 6.25 mg/mL, with a better inhibitory effect at higher concentrations. Similar findings were also reported by [PERSON] et al. [29] during their studies on biofilm inhibition. They discovered that TXA inhibited biofilm formation at concentrations equal to or higher than 10 mg/mL in a dose-dependent manner. Moreover, they suggested that inhibition was due to the suppression of proteins and polysaccharide components. TXA at concentrations of 25 mg/mL and 50 mg/mL was also successful in biofilm prevention in an in vivo mouse implant-associated model. However, this study was performed only on two _S. aureus_ strains.