Non-Antimicrobial Drugs: Etodolac as a Possible Antimicrobial or Adjuvant Agent Against ESKAPE Pathogens

Multiple-drug resistant bacteria are emerging exponentially in healthcare units, threatening public health and requiring novel therapeutic approaches. In 2017, World Health Organization published a list that frames antimicrobial resistant bacteria into priority levels for research of novel drugs to fight them.

Antimicrobial resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter sp.) and Enterococcus faecalis and Escherichia coli pathogens are present in this list. Representative isolates of each species were used to test the Antibacterial and anti-biofilm formation activities of Etodolac (a Non-Steroidal Anti-Inflammatory Drug, NSAID) at 10 and 1 mM using a broth microdilution technique.

Statistically significant (p< 0,05) results were observed against all tested gram-positives, particularly anti-biofilm activity against E. faecium. Etodolac had an almost null influence on tested gram-negatives, with the exception of one A. baumannii clinical isolate regarding biofilm formation inhibition. Observed differences deserve further analysis and prospection of the involved mechanisms, to unravel possible novel bacterial targets for drug development. Similar work with other NSAID's may also be worth exploring to ascertain novel therapeutic applications for these drugs, particularly regarding biofilm formation inhibition, per si or as adjuvants of current antibiotherapy, mainly against gram-positives, as suggested by present work.

Already approved drugs in terms of pharmacokinetics and safety may deploy faster solutions for antimicrobial therapy against priority pathogens. Current work intends to bring attention to that possibility, particularly regarding NSAIDs, anti-biofilm formation and top priority pathogens.