Tranexamic acid protects against implant-associated infection by reducing biofilm formation

Wang, Jiahao; Zhang, Zhen; Li, Jingyi; Huang, Biying; Jiang, Zhiyuan; Pan, Yixiao; He, Tailai; Hu, Yihe; Wang, Long

doi:10.1038/s41598-022-08948-w

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…It has been hypothesized that TXA reduces surgical site infections by reducing surgical site bleeding and subsequent biofilm formation, which may be especially critical in implant-associated infections [ 20 ]. Central venous access devices can also serve as a nidus for biofilm formation and infection [ 21 ], which may play a role in patients with hematologic malignancy, given widespread use of central venous catheters.…”

Section: Discussionmentioning

confidence: 99%

Fewer severe infections with tranexamic acid in patients with hematologic malignancies

Poston,

Brown,

Ilich

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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Section: Discussionmentioning

confidence: 99%

Fewer severe infections with tranexamic acid in patients with hematologic malignancies

Poston,

Brown,

Ilich

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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“…However, in the present study, we decided to analyze the synergistic effect of 10 mg/ml TXA with these antibiotics against a large collection of clinical strains isolated from patients with musculoskeletal infection. We used a 10-mg/ml concentration for a number of reasons: first, because we had previously demonstrated that it had a direct antibacterial effect on planktonic cells and that its effect was not dose-dependent (Benjumea et al, 2022a ; Wang et al, 2022 ); second, because it has been shown that ≥20 mg/ml can cause cellular toxicity (to chondral cells, epithelial cells, and fibroblasts), with the result that wound healing capacity could be compromised at higher doses (Parker et al, 2018 ; Eikebrokk et al, 2019 ; Bolam et al, 2021 ); and, third, because 10 mg/ml is the most widely used concentration in clinical studies (Sun et al, 2017 ; Montroy et al, 2018 ; Masaryk et al, 2022 ; Bi et al, 2023 ). Our analysis showed an overall reduction in turbidity of 10.9% for S. aureus and 2.2% for S. epidermidis strains when treated with TXA alone.…”

Section: Discussionmentioning

confidence: 99%

“…We tested 10 mg/ml TXA (shown to be optimal) (Benjumea et al, 2022a , b ; Wang et al, 2022 ) following CLSI guidelines using a microtiter plate (Clinical and Laboratory Standards Institute, 2018 ). The wells of a 96-well plate were inoculated with 50 μl of a suspension of 10 7 cfu/ml of each microorganism in Müller-Hinton broth and treated with 50 μl of 20 mg/ml TXA (as the final dose in the well will be 10 mg/ml).…”

Section: Methodsmentioning

confidence: 99%

“…Based on the reported decrease in postoperative hematoma, some authors believe this is due to an indirect effect (Klement et al, 2020 ; Lacko et al, 2020 ; Sukeik et al, 2020 ; Yazdi et al, 2020 ). Other authors reported that TXA exerts a direct antibacterial effect on planktonic cells (Zhang et al, 2021 ; Benjumea et al, 2022b ; Wang et al, 2022 ) and, moreover, that it produces a synergistic effect with antibiotics (Benjumea et al, 2022a ). However, these results need to be validated.…”

Section: Introductionmentioning

confidence: 99%

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Validation of the antibacterial effect of topically applied tranexamic acid using in vitro and in vivo models

Benjumea,

Díaz-Navarro,

Gago-Campos

et al. 2024

Front. Microbiol.

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BackgroundSeveral studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model.MethodsWe tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM).ResultsWhen TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin.ConclusionWe confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.

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“…Biofilm, an organized colony of microorganisms, forms an extracellular polymeric matrix of substance and shows adhesion with the neighbouring living and non-living surfaces 15 . It facilitates microorganism interaction and protect tolerant cells from the change in living environment for a long period of time 16 . The biofilm matrix strengthen the tolerance to disinfectants by wrapping the underlying cells 17 , 18 and by restricting diffusion of disinfectants into the biofilm matrix 19 .…”

Section: Introductionmentioning

confidence: 99%

Molecular co-localization of multiple drugs in a nanoscopic delivery vehicle for potential synergistic remediation of multi-drug resistant bacteria

Banerjee

Mukherjee

Bera

et al. 2022

Sci Rep

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Anti-microbial resistant infection is predicted to be alarming in upcoming years. In the present study, we proposed co-localization of two model drugs viz., rifampicin and benzothiazole used in anti-tuberculosis and anti-fungal agents respectively in a nanoscopic cationic micelle (cetyl triethyl ammonium bromide) with hydrodynamic diameter of 2.69 nm. Sterilization effect of the co-localized micellar formulation against a model multi-drug resistant bacterial strain viz., Methicillin resistant Staphylococcus aureus was also investigated. 99.88% decrease of bacterial growth in terms of colony forming unit was observed using the developed formulation. While Dynamic Light Scattering and Forsters Resonance Energy Transfer between benzothiazole and rifampicin show co-localization of the drugs in the nanoscopic micellar environment, analysis of time-resolved fluorescence decays by Infelta-Tachiya model and the probability distribution of the donor–acceptor distance fluctuations for 5 μM,10 μM and 15 μM acceptor concentrations confirm efficacy of the co-localization. Energy transfer efficiency and the donor acceptor distance are found to be 46% and 20.9 Å respectively. We have also used a detailed computational biology framework to rationalize the sterilization effect of our indigenous formulation. It has to be noted that the drugs used in our studies are not being used for their conventional indication. Rather the co-localization of the drugs in the micellar environment shows a completely different indication of their use in the remediation of multi-drug resistant bacteria revealing the re-purposing of the drugs for potential use in hospital-born multi-drug resistant bacterial infection.

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Tranexamic acid protects against implant-associated infection by reducing biofilm formation

Cited by 10 publications

References 24 publications

Fewer severe infections with tranexamic acid in patients with hematologic malignancies

Fewer severe infections with tranexamic acid in patients with hematologic malignancies

Validation of the antibacterial effect of topically applied tranexamic acid using in vitro and in vivo models

Molecular co-localization of multiple drugs in a nanoscopic delivery vehicle for potential synergistic remediation of multi-drug resistant bacteria

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