Impact of erdostein on bacterial biofilm − and what it means for clinical practice?

Bacterial biofilm as a major problem in clinical practice

Bacterial biofilms represent a serious problem because infections accompanied by their formation lead to persistent, recurrent, and difficult-to-treat conditions that are poorly sensitive to antimicrobial therapy. As a result, many scientific teams aim to find ways to prevent biofilm formation and develop new strategies to enhance the effectiveness of available treatments. Due to the unique properties of biofilm, simple antibiotic (ATB) monotherapy does not yield the desired results.

The reason is both the protective effect of the extracellular polymeric matrix, which encapsulates pathogenic organisms' cells and hinders ATB penetration through the biofilm (potentially directly inhibiting their action through enzymes, for example), and the heterogeneity of biofilm composition in terms of the metabolic state of individual cells. Studies have shown that biofilm cells can be up to 1000 times more resistant to ATB effects than free-floating cells. Moreover, different gene expressions in planktonic cells and cells attached within the biofilm can also play a role.

Mechanism of action of erdostein

Erdostein is an oral mucolytic agent. It is a prodrug that transforms into active metabolites (especially Met 1) containing a thiol (sulfhydryl) group in the body. The action of free thiol groups disrupts the disulfide bridges of glycoproteins present in bronchial mucus, reducing its viscosity and elasticity. The medication also promotes mucociliary transport.

Thiol groups are also responsible for the antioxidant properties of erdostein metabolites, as they scavenge free oxygen radicals and simultaneously prevent their formation. Anti-inflammatory effects of erdostein have also been described − experimentally, a decrease in levels of pro-inflammatory cytokines, such as interleukins IL-6 and IL-8 or tumor necrosis factor-alpha (TNF-α), has been confirmed.

Potentiation of ATB effect

From the perspective of applying erdostein in treating infections associated with biofilm formation, crucial studies have confirmed its ability to improve the penetration of certain types of antibiotics (such as amoxicillin, clarithromycin, or ciprofloxacin) into the biofilm biomass, ensuring their higher efficacy. However, the exact mechanism leading to increased ATB efficacy against biofilm has not yet been elucidated.

Several factors are assumed to play a role. The first is related to the ability of biologically active metabolites of erdostein to affect disulfide bridges. The extracellular matrix of the biofilm, like bronchial mucus, contains many disulfide bonds that contribute to stabilizing the structure of its components. Affecting the structure of the biofilm's extracellular matrix can help improve ATB penetration and effectiveness. Another factor is erdostein's antioxidant activity, as oxidative stress affects the production of the extracellular matrix. The efficacy of ATB in treating infections associated with biofilm formation is further enhanced by erdostein's potential to negatively affect bacteria's ability to adhere to the respiratory mucosa. Thiol groups, which weaken the bonds bacteria use to attach to epithelial surfaces via fimbriae, are again responsible for this anti-adhesive effect.

Conclusion

Many details related to the mechanism of action of erdostein combined with antibiotic therapy for infections associated with biofilm formation must still be clarified. And there is no doubt that the results will vary depending on the pathogenic organism and biofilm's extracellular matrix composition. However, based on existing knowledge, erdostein has already emerged as a justified and important component of these diseases' therapies.

(eub)

Sources:
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