Diclofenac Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactams and Prevents Implant Infections

Area of Science:

• Infectious Diseases
• Pharmacology
• Biotechnology

Background:

• Implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) pose significant perioperative risks.
• Diclofenac, a widely used nonsteroidal anti-inflammatory drug (NSAID), is employed for pain and inflammation management.

Purpose of the Study:

• To investigate the effects of diclofenac on MRSA growth, resistance, and biofilm formation.
• To evaluate the potential of diclofenac, alone and in combination with beta-lactams, for treating MRSA implant infections.

Main Methods:

• In vitro studies assessing MRSA growth inhibition and resistance mutation induction by diclofenac.
• Transcriptomic and proteomic analyses to elucidate diclofenac's molecular mechanisms.
• Murine implant infection models to evaluate in vivo efficacy of diclofenac combined with beta-lactams.

Main Results:

• High-dose diclofenac inhibited MRSA growth without readily inducing resistance.
• Low-dose diclofenac resensitized MRSA to beta-lactams and inhibited biofilm formation.
• Diclofenac and beta-lactams demonstrated synergistic effects, reducing MRSA implant infections in vivo.

Conclusions:

• Diclofenac exhibits multitarget effects against MRSA, including growth inhibition and overcoming beta-lactam resistance.
• Low-dose diclofenac combined with beta-lactams shows promise for preventing and treating MRSA implant infections.
• The synergistic action of diclofenac and beta-lactams offers a potential strategy for combating antibiotic resistance in implant-associated infections.