Brodimoprim synergy against Enterococcus faecalis evaluated in vitro

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Enterococcus faecalis is a common cause of various infections.
• Antibiotic resistance in E. faecalis necessitates novel therapeutic strategies.
• Understanding synergistic interactions is crucial for effective treatment regimens.

Purpose of the Study:

• To evaluate the synergistic antibacterial activity of brodimoprim and trimethoprim in combination with other antibiotics against Enterococcus faecalis.
• To compare the efficacy of brodimoprim and trimethoprim in potentiating the activity of antibiotics.
• To investigate the mechanism underlying the enhanced activity of brodimoprim combinations.

Main Methods:

• Checkerboard synergy testing to determine Minimum Inhibitory Concentrations (MICs) and Minimum Bactericidal Concentrations (MBCs).
• Viable count determinations to assess bacterial regrowth over 24 hours.
• ATP release assays to measure bacterial cell membrane integrity.

Main Results:

• Synergistic activity was observed for brodimoprim and trimethoprim in combination with carbenicillin, ciprofloxacin, and rifampicin against E. faecalis.
• Brodimoprim exhibited greater antibacterial activity than trimethoprim, both alone and in combination.
• Combinations, particularly with brodimoprim, prevented bacterial regrowth and led to increased ATP release, indicating compromised cell permeability.

Conclusions:

• Brodimoprim and trimethoprim, especially brodimoprim, show significant potential for combination therapy against E. faecalis infections.
• The enhanced activity of brodimoprim combinations may be attributed to increased bacterial cell permeability.
• These findings support the development of brodimoprim-based combination therapies for E. faecalis infections.