BRODIMOPRIM SYNERGY AGAINST ENTEROCOCCUS-FAECALIS EVALUATED IN-VITRO

Combinations of either brodimoprim or trimethoprim plus either carbeni cillin, gentamicin, ciprofloxacin or rifampicin showed synergy at sub- inhibitory concentrations against both Enterococcus faecalis NCTC 5957 and 775. Brodimoprim alone and in combination showed greater antibact erial activity against both strains of E. faecalis than trimethoprim. MBCs of brodimoprim and trimethoprim were 14.4 and 25.6 mg/L for E. fa ecalis NCTC 5957 and 7.2 and 12.8 mg/L for E. faecalis NCTC 775. Combi nations of either brodimoprim or trimethoprim plus the other antibacte rial agents, except gentamicin and dibromopropamidine isethionate, wer e bactericidal at achievable plasma concentrations. Viable count deter minations of cultures of both test organisms in the presence of 3/4 of the MIC of each of the four antibiotics and the two antifolates alone and combinations of each antibiotic with either brodimoprim or trimet hoprim indicated that only the combinations prevented recovery and reg rowth of the cultures over 24 h. The ATP released from cultures of bot h strains of E. faecalis treated with brodimoprim and trimethoprim at the same concentrations was approximately 1.5 times greater with brodi moprim than with trimethoprim. Combinations of 3/4 of the MIC of each of the antibiotics in combination with 3/4 of the MIC of brodimoprim a gainst cultures of both strains of E. faecalis resulted in greater rel ease of ATP than occurred with equivalent trimethoprim combinations. I t is postulated that the increased activities observed with the brodim oprim combinations resulted from an effect of brodimoprim on the bacte rial cell permeability control. These results indicate that both brodi moprim and trimethoprim offer potential benefits for use with either c arbenicillin, gentamicin, ciprofloxacin or rifampicin for the treatmen t of E. faecalis infections.