NSAIDs as a Drug Repurposing Strategy for Biofilm Control

Abstract

Persistent infections, usually associated with biofilm-producing bacteria, are challenging for both medical and scientific communities. The potential interest in drug repurposing for biofilm control is growing due to both disinvestment in antibiotic R&D and reduced efficacy of the available panel of antibiotics. In the present study, the antibacterial and antibiofilm activities of four non-steroidal anti-inflammatory drugs (NSAIDs), piroxicam (PXC), diclofenac sodium (DCF), acetylsalicylic acid (ASA) and naproxen sodium (NPX) were evaluated against Escherichia coli and Staphylococcus aureus. The minimum inhibitory/bactericidal concentrations (MICs and MBCs) and the dose–response curves from exposure to the selected NSAIDs were determined. MICs were found for PXC (800 μg/mL) and ASA (1750 μg/mL) against E. coli, and for DCF (2000 μg/mL) and ASA (2000 μg/mL) against S. aureus. No MBCs were found (>2000 μg/mL). The potential of NSAIDs to eradicate preformed biofilms was characterized in terms of biofilm mass, metabolic activity and cell culturability. Additionally, the NSAIDs were tested in combination with kanamycin (KAN) and tetracycline (TET). ASA, DCF and PXC promoted significant reductions in metabolic activity and culturability. However, only PXC promoted biofilm mass removal. Additive interactions were obtained for most of the combinations between NSAIDs and KAN or TET. In general, NSAIDs appear to be a promising strategy to control biofilms as they demonstrated to be more effective than conventional antibiotics.

The Drug-Loaded Electrospun Poly(ε-Caprolactone) Mats for Therapeutic Application

“…The antimicrobial activity of diclofenac sodium salt was described by many authors [ 74 , 75 ]. In this study, the antimicrobial activity of the electrospun pure PCL and DSS-loaded PCL mats was tested against S. aureus and E. coli by the contact method according to ISO 22196:2011.…”

Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing

“…Pseudomonas aeruginosa Soheili et al, 2015;Belfield et al, 2017;Fourie et al, 2017;Ulusoy et al, 2017;Pereira et al, 2018;She et al, 2018;Abidi et al, 2019;Dai et al, 2019;Gerner et al, 2020 Staphylococcus aureus Belfield et al, 2017;Dotto et al, 2017;Xu et al, 2017;Cai et al, 2018;Oliveira et al, 2019;Abbas et al, 2020;Tzeng et al, 2020 Candida spp. Rosato et al, 2016;Fourie et al, 2017;Brilhante et al, 2020;Lin et al, 2020;Santos et al, 2020 Escherichia coli Cattò et al, 2017;Pereira et al, 2018;Leão et al, 2020…”

“…Acetylsalicylic acid Rosato et al, 2016;Yang et al, 2016;Belfield et al, 2017;Dotto et al, 2017;Fourie et al, 2017;Xu et al, 2017;Cai et al, 2018;Abidi et al, 2019;Leão et al, 2020;Lin et al, 2020;Santos et al, (Gerner et al, 2020). A previous report demonstrated that the growth of P. aeruginosa in the presence of salicylate reduced the production of extracellular polysaccharides required for biofilm formation (Pereira et al, 2018 (200,175, and 150 µg/ml, respectively).…”

“…However, although the available in vitro data can create some enthusiasm on the prospects of repurposing NSAIDs as antibiofilm agents, these observations can hardly be translated into clinical practice as it stands. Data on NSAIDs' in vitro activity against planktonic bacteria and biofilms are not consistent (Riordan et al, 2011;Belfield et al, 2017;Abbas et al, 2020;Gerner et al, 2020;Leão et al, 2020). In addition, there is evidence showing the selection of resistant bacterial populations following exposure to NSAIDs (Cohen et al, 1993;Gustafson et al, 1999;Helal, 2012;Belfield et al, 2017;Verma et al, 2018).…”

Synergistic Activity of New Diclofenac and Essential Oils Combinations against Different Candida spp.

“…Recently, the activity of different drugs belonging to other therapeutic classes are being evaluated in the drugs-repositioning strategy as antimicrobials [7]. Drugs such as Promazine (phenothiazine antipsychotic), Promethazine (antihistamine), Methyldopa (centrally acting antidepressant), Dobutamine (sympathomimetic) and Diclofenac (NSAIDs) have shown an interesting antimicrobial activity, and for this reason they have been defined as non-antibiotic drugs [8][9][10][11][12]. According to these results, Diclofenac, also known as (2-[2-(2,6-dichloroanilino)phenyl] acetic acid), one of the more effective cyclooxygenase enzymes (COX) inhibitors, was selected for this research.…”