Effects of Tranexamic Acid in Combination with Teicoplanin Against Staphylococcus isolates: Results from an In Vitro...

Staphylococcus epidermidis is a major cause of periprosthetic and other implant-associated orthopedic infections because of its ability to adhere to biomaterial surfaces and form biofilm. Tranexamic acid (TXA) is routinely used in arthroplasty to reduce perioperative blood loss; however, emerging evidence suggests that it may also modulate bacterial behavior and antibiotic activity. This study investigated the in vitro effects of TXA in combination with teicoplanin on planktonic growth and biofilm biomass formation in clinical Staphylococcal isolates. Clinical Staphylococcal isolates were evaluated using disk diffusion assays, microtiter plate-based planktonic growth assays, and crystal violet biofilm biomass assays. Microplate-based growth and biofilm assays were performed using five clinical isolates, whereas disk diffusion assays were performed using a separate set of seven clinical staphylococcal isolates. Teicoplanin was tested at literature-based low concentrations of 0.1 and 0.4 µg/mL, either alone or in combination with TXA at 10 and 50 mg/mL. In disk diffusion assays, inhibition zone diameters were quantified using ImageJ. Planktonic growth was assessed by optical density at 600 nm, and biofilm biomass accumulation was quantified by crystal violet staining at 570 nm. Disk diffusion data were analyzed using paired t-tests, while microplate-based growth and biofilm data were analyzed using two-way analysis of variance (ANOVA) followed by Tukey's multiple-comparisons test. In disk diffusion assays, TXA co-application was associated with larger teicoplanin inhibition zones on both blood agar and Mueller-Hinton agar, suggesting an increased apparent inhibitory zone under agar-based conditions. In microplate-based planktonic growth assays, responses were isolate-dependent. However, co-exposure to TXA, particularly at 50 mg/mL, was associated with reduced OD600-based bacterial growth in several isolates compared with teicoplanin alone. A similar isolate-dependent pattern was observed for crystal violet-based biofilm biomass accumulation. In most tested isolates, teicoplanin combined with 50 mg/mL TXA was associated with lower biofilm biomass than teicoplanin alone, whereas one isolate showed minimal responsiveness. Under the tested in vitro conditions, TXA-teicoplanin co-exposure was associated with reduced planktonic growth and crystal violet-based biofilm biomass accumulation in several clinical staphylococcal isolates. However, because TXA-only controls were not available across the full experimental framework and formal synergy assays were not included, these findings do not establish synergistic activity or distinguish combination-specific effects from TXA-associated effects alone. Further studies are needed to clarify the biological and translational relevance of these observations.