Can Erdostein Help in Treating Infections Related to Biofilm Formation?

Advantageous for Bacteria, Disadvantageous for Humans

Biofilm contributes to the formation of infections in the human population by more than 80%. It is a biological structure representing a community of a larger number of microbial cells, which are firmly attached to a surface or to each other and enveloped in an extracellular matrix created by these microorganisms' products. It serves to protect microbes from adverse environmental influences and is often compared to a kind of housing for the microbial community, where its members are able to communicate and change their properties.

The composition of the extracellular matrix, and thus the physiological properties of biofilms and their defense capabilities against external influences, vary. Some, for instance, inhibit the function of leukocytes through various mechanisms. They may also be able to use efflux pumps to remove substances undesirable for the microbes, including antibiotics, from their interiors. All of this complicates the treatment of infections caused by pathogens capable of biofilm formation. Biofilms are resistant to antibiotics, thus standalone antibiotic treatment is only marginally effective in this case. It is necessary to look for agents that can penetrate it.

Bacteria and Infections Associated with Biofilm Formation

Both gram-positive and gram-negative bacteria can create biofilms. Among the most common microbes producing biofilms, which cause human infections, are the following:

• Enterococcus faecalis
• Staphylococcus aureus
• Staphylococcus epidermidis
• Streptococcus viridans
• Escherichia coli
• Klebsiella pneumoniae
• Proteus mirabilis
• Pseudomonas aeruginosa

Pathogens capable of creating biofilms are often linked to chronic, frequently nosocomial infections. They are especially problematic for patients with implants, catheters, and prosthetics. It is estimated that S. aureus and S. epidermidis strains cause 40-50% of valve replacement infections, 50-70% of catheter-related infections, and 87% of bloodstream infections. Biofilm formation plays a significant role in infections causing rhinosinusitis, endocarditis, osteomyelitis, meningitis, kidney infections, periodontitis, and chronic non-healing wounds.

According to a study published in 2018, which examined nosocomial infections caused by S. aureus, more than 99.2% of 130 tested strains of this bacterium were capable of biofilm production. For methicillin-resistant S. aureus (MRSA), 39.7% formed a strong biofilm, while for methicillin-sensitive S. aureus (MSSA), 36.8% of strains formed strong biofilms. The highest proportion of strong biofilm producers was found in strains isolated from sputum and tracheostomy cannula (66.7%), followed by those from the nose and catheter (50%), throat (44.4%), and bronchoalveolar lavage (43.8%).

How to Penetrate to Microbes?

Biofilms are resistant to the endogenous defense of the host organism. As mentioned earlier, such a protected microbial community has adaptability capabilities. It appears that large doses of antibiotics, which were used in an attempt to cure biofilm-based resistant infections, contributed to the emergence of resistant strains. Furthermore, it was found that dormant variants of cells were created within the biofilm, which not only exhibited tolerance to antibiotics (ATB) but also had the ability to reactivate after therapy cessation.

A recent study, published in March 2022, concluded that erdostein, with its multifunctional pharmacodynamic properties and mucolytic, anti-inflammatory, and antioxidant effects, shows potential in the treatment of biofilm-related infections. This in vitro study evaluated the effect of erdostein in combination with various ATBs against biofilms created by MRSA and MSSA. For MRSA, erdostein was tested in combination with vancomycin and linezolid, and against MSSA it was tested with amoxicillin/clavulanate ATBs and levofloxacin. It was shown that standalone ATBs had significantly lower penetrative capabilities into the biofilm compared to combinations including erdostein.

Researchers are testing various methods of disrupting biofilm, which are often difficult to apply in routine primary care practice. These include the use of electromagnetic fields, ultrasound, or photodynamics. Notable interest is also in creating surface modifications for bioimplants, which would prevent biofilm adhesion to their surfaces.

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Sources:
1. Pani A., Lucini V., Dugnani S., Scaglione F. Erdosteine enhances antibiotic activity against bacteria within biofilm. Int J Antimicrob Agents 2022 Mar; 59 (3): 106529, doi: 10.1016/j.ijantimicag.2022.106529. 
2. Piechota M., Kot B., Frankowska-Maciejewska A. et al. Biofilm formation by methicillin-resistant and methicillin-sensitive Staphylococcus aureus strains from hospitalized patients in Poland. Biomed Res Int 2018: 4657396, doi: 10.1155/2018/4657396. 
3. Kvasničková E. Biofilmy: Život mikroorganismů v jednotném společenství. Vysoká škola chemicko-technologická, 2016. Available at: www.vscht.cz/popularizace/doktorandi-pisou/biofilmy
4. Khatoon Z., McTiernan C. D., Suuronen E. J. et al. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon 2018; 4 (12): e01067, doi:10.1016/j.heliyon.2018.e01067.