The effect of a thiol-based combination treatment on medically important biofilm-forming bacteria

Abstract

In 2017, the World Health Organisation officially published a list of highly virulent, multi-drug resistant organisms considered responsible for increasing therapeutic failure worldwide. Of these include six clinically significant, biofilm-forming bacterial pathogens identified as the ESKAPE species (Enterococcus faecium or Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). Rising costs, increased antibiotic resistance, recalcitrant biofilms, prolonged length of stay, exhausting public health budget and staff, limited treatment options, and increased patient morbidity and mortality are just some of the direct consequences of combating the ESKAPE species.

The in vitro studies presented here utilised a novel treatment comprised of a two-part combination therapy consisting of an antioxidant (either glutathione or N-acetyl cysteine), and an antibiotic (either amikacin or ciprofloxacin) over a range of concentrations to disrupt biofilms formed by isolates from all ESKAPE species and eradicate underlying bacterial cells. A three-part combination therapy which included 40U of the enzyme DNase-I was also studied. The resulting data presented here demonstrated that two-part combination therapy was particularly effective with either antioxidant at 30 mM, and resulted in significant reductions in biofilm viability and biomass across all ESKAPE pathogens, while also reducing the concentration of antibiotic required. In the case of A. baumannii, only a third of antibiotic (4 µg/mL) was necessary in the successful disruption of biofilm viability when applied in combination therapy.

These findings may help pave the way for future in vivo animal trials and if successful, in human clinical trials, and therefore, potentially provide an alternative therapeutic treatment for ESKAPE species forming recalcitrant biofilms.