Assessment of anti-MRSA activity of auranofin and florfenicol combination: a PK/PD analysis

Area of Science:

• Antimicrobial resistance
• Infectious diseases
• Pharmacology

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) is a significant zoonotic pathogen.
• Multidrug-resistant MRSA strains are increasingly common in human and veterinary medicine.

Purpose of the Study:

• To evaluate auranofin (AF) as an antibiotic adjuvant to boost the anti-MRSA activity of florfenicol (FFC).
• To establish a pharmacokinetic/pharmacodynamic (PK/PD) model comparing FFC alone versus FFC combined with AF against MRSA.

Main Methods:

• Assessed MRSA susceptibility to FFC in the presence of AF.
• Investigated the impact of FFC-AF combination on MRSA biofilm formation and metabolic activity.
• Evaluated efficacy in Galleria mellonella larvae and murine models.
• Developed a PK/PD model to determine efficacy targets.

Main Results:

• AF significantly enhanced MRSA susceptibility to FFC, demonstrating synergistic effects.
• The FFC-AF combination effectively inhibited MRSA biofilm formation and reduced metabolic activity.
• AF restored FFC efficacy in vivo (G. mellonella and murine models).
• PK/PD analysis showed lower AUC24h/MIC targets for bacteriostatic and bactericidal effects with combination therapy.

Conclusions:

• Auranofin shows potential as a novel adjuvant to improve FFC efficacy against MRSA invasive infections.
• Valuable PK/PD insights were gained for designing effective FFC-AF combination therapies.