Florfenicol As a Modulator Enhancing Antimicrobial Activity: Example Using Combination with Thiamphenicol against...

Area of Science:

• Microbiology
• Pharmacology
• Veterinary Medicine

Background:

• Synergistic antibiotic effects within the same class are uncommon.
• Previous research indicated a synergistic-like interaction between florfenicol (FFC) and thiamphenicol (TAP) against Staphylococcus aureus.

Purpose of the Study:

• To evaluate the enhanced antimicrobial activity of FFC and TAP combinations against a wider range of bacterial pathogens.
• To investigate the potential of FFC as a modulator in novel antibiotic combination regimens.

Main Methods:

• Checkerboard microdilution assay to identify susceptible strains (FICI ≤ 0.625).
• Time-kill methodology to confirm synergistic bactericidal effects (≥2 log10 CFU/ml reduction).
• In vivo chicken fowl cholera models and in vitro studies with Pseudomonas aeruginosa.

Main Results:

• 43% of Pasteurella multocida isolates showed enhanced susceptibility to the FFC-TAP combination.
• The FFC-TAP combination demonstrated significant protection in vivo at reduced dosages.
• Synergistic activity of FFC with oxytetracycline (OTC) against Pseudomonas aeruginosa was confirmed in vitro.

Conclusions:

• Florfenicol (FFC) can act as an initiating modulator, enhancing the activity of other antibiotics against both Gram-positive and Gram-negative bacteria.
• The FFC combination therapy improved bacteriostatic effects to bactericidal and extended effectiveness to FFC-resistant strains.
• Further research is warranted to explore the mechanisms, such as bacterial membrane permeability alterations, and the full potential of FFC-based combination therapies.