Brodimoprim synergy against Enterococcus faecalis evaluated in vitro

• Published in: Journal of antimicrobial chemotherapy 1996-07, Vol.38 (1), p.27-37
• Main Authors: Richards, R. M. E., Xing, J. Z.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Carbenicillin - pharmacology; Ciprofloxacin - pharmacology; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecalis - drug effects; Enzyme Inhibitors - pharmacology; Evaluation Studies as Topic; Folic Acid Antagonists - pharmacology; Gentamicins - pharmacology; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Rifampin - pharmacology; Trimethoprim - analogs & derivatives; Trimethoprim - pharmacology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/38.1.27

Combinations of either brodimoprim or trimethoprim plus either carbenicillin, 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 antibacterial activity against both strains of E. faecalis than trimethoprim. MBCs of brodimoprim and trimethoprim were 14.4 and 25.6 mg/L for E. faecalis NCTC 5957 and 7.2 and 12.8 mg/L for E. faecalis NCTC 775. Combinations of either brodimoprim or trimethoprim plus the other antibacterial agents, except gentamicin and dibromopropamidine isethionate, were bactericidal at achievable plasma concentrations. Viable count determinations 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 trimethoprim indicated that only the combinations prevented recovery and regrowth of the cultures over 24 h. The ATP released from cultures of both strains of E. faecalis treated with brodimoprim and tnmethoprim at the same concentrations was approximately 1.5 times greater with brodimoprim 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 against cultures of both strains of E. faecalis resulted in greater release of ATP than occurred with equivalent trimethoprim combinations. It is postulated that the increased activities observed with the brodimoprim combinations resulted from an effect of brodimoprim on the bacterial cell permeability control. These results indicate that both brodimoprim and trimethoprim offer potential benefits for use with either carbenicillin, gentamicin, ciprofloxacin or rifampicin for the treatment of E. faecalis infections.