Erdosteine enhances antibiotic activity against bacteria within biofilm

Int J Antimicrob Agents. 2022 Mar;59(3):106529. doi: 10.1016/j.ijantimicag.2022.106529. Epub 2022 Jan 17.

Abstract

Bacterial biofilms form on inert and living surfaces and display high levels of resistance to antibiotics, making it difficult to eradicate biofilm-related infections. Erdosteine, a thiol-based drug used in the treatment of acute and chronic respiratory diseases, has multiple pharmacodynamic properties (mucolytic, anti-inflammatory, antioxidant), suggesting that it may have potential in controlling biofilm-related infections. This in vitro study aimed to evaluate the effects of erdosteine in combination with different antibiotics against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) biofilms. Biofilm production/mass and bacterial viability were measured using crystal violet absorbance and resorufin resonance, respectively, in young (6 h) and mature (24 h) biofilms incubated with antibiotics [at concentrations from 0 to 200 times the minimum inhibitory concentration (MIC)] for 24 h in the absence or presence of erdosteine (2, 5 and 10 mg/L). In 6-h MRSA biofilms, vancomycin and linezolid displayed concentration-dependent reductions in biofilm mass and viability, which was enhanced in the presence of increasing concentrations of erdosteine. Similar results were seen for amoxicillin/clavulanate and levofloxacin against 6-h MSSA biofilms. Antibiotics alone had reduced efficacy against 24-h biofilms, while the effect of the erdosteine-antibiotic combination was significantly greater against 24-h biofilms (MRSA and MSSA). These results suggest that erdosteine enhances the activity of the antibiotic by facilitating its penetration into biofilms and by disrupting the extracellular polymeric substance matrix, which should be confirmed with further studies. The potential clinical value of erdosteine in treating biofilm-related infections warrants further investigation.

Keywords: Antibiotic resistance; Biofilm; Erdosteine; MRSA; MSSA; Staphylococcus aureus.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Biofilms
  • Extracellular Polymeric Substance Matrix
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Thioglycolates
  • Thiophenes

Substances

  • Anti-Bacterial Agents
  • Thioglycolates
  • Thiophenes
  • erdosteine