Effect of tranexamic acid on planktonic and biofilm susceptibility of Candida albicans

BACKGROUND: Fungal periprosthetic joint infection remains a challenging complication in revision arthroplasty. Candida albicans (C. albicans) is among the most frequently reported fungal pathogens, and biofilm formation further limits antifungal efficacy. Tranexamic acid (TXA) is routinely used to reduce perioperative blood loss in arthroplasty and may come into direct contact with antifungal agents within the joint environment. However, whether TXA modifies antifungal activity against C. albicans remains unclear. This study aimed to evaluate the effect of TXA on the in vitro activity of representative antifungal agents against C. albicans under planktonic and established biofilm conditions. RESULTS: Baseline planktonic MICs for FLC, VRC, CAS, and AMB were 0.75, 0.5, 1, and 0.75 µg/mL, respectively. In the presence of TXA, susceptibility shifts were class-dependent: MICs for VRC and CAS decreased four-fold and two-fold, respectively, while AMB exhibited a two-fold increase and FLC remained unchanged. Established biofilms showed markedly reduced antifungal susceptibility, and TXA further altered the XTT-derived biofilm metabolic inhibition profiles. For FLC, TXA increased peak metabolic inhibition from approximately 50-55% in saline to 85-90%, with an XTT-derived MBEC₉₀ of 192 µg/mL. In contrast, TXA attenuated VRC-mediated biofilm metabolic inhibition, producing a right-shifted dose-response profile relative to saline conditions. For CAS, TXA lowered the XTT-derived activity threshold from 256 to 128 µg/mL, although the response curves converged at higher concentrations. For AMB, TXA reduced apparent biofilm activity, increasing the XTT-derived minimum biofilm eradication concentrations (MBECs) threshold from 1.5 to 12 µg/mL. CONCLUSIONS: TXA differentially modulated the apparent in vitro activity of representative antifungal agents against C. albicans in an antifungal class- and growth-state-dependent manner. The discordance between planktonic and antibiofilm responses under TXA co-exposure supports further mechanistic and translational validation in clinically relevant Candida biofilm models.