Antimicrobial and antibiofilm activities of paracetamol in combination with various antimicrobials

Background and Aims: In recent years, very few new antimicrobial agents have been approved and used for the treatment of infectious diseases. Paracetamol (acetaminophen) is one of the nonsteroidal anti inflammatory drugs with analgesic and antipyretic effects, which is frequently preferred and used safely in our country and in many other countries. In addition, because it is the most frequently prescribed drug after antibiotics and is often administered with antimicrobial therapy, understanding the interactions between these two drug classes is extremely important for drug repurposing. Methods: For this purpose, the effects of paracetamol alone or in combination with various antimicrobial agents and their activities on adhesion and biofilm formation were investigated against various standard bacteria and yeasts. Results: The minimum inhibitory concentration of paracetamol against standard strains was found 10,000 μg/mL, and the minimum bactericidal and fungicidal concentrations were found 10,000 - > 20,000 μg/mL. Cefepime and paracetamol combinations against Escherichia coli and Achromobacter xylosoxidans, and gentamicin and paracetamol combinations against Klebsiella pneumoniae and Acinetobacter baumannii showed synergistic effect. No antagonism was observed. According to the biofilm adhesion and formation inhibition assays, it was found that paracetamol was more effective against gram-negative bacteria than gram-positive bacteria and yeasts. Conclusions: In conclusion, this study proved that paracetamol, which is one of the most common analgesic and antipyretic agents in clinical use for many years, has antimicrobial and antibiofilm activity and can show synergistic effect in combination with various antibiotics.