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Therapeutic Methods and Therapies TCIM
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1.
J Antimicrob Chemother ; 68(6): 1312-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23447139

ABSTRACT

OBJECTIVES: Reduction in faecal shedding of Shiga toxin-producing enterohaemorrhagic Escherichia coli (EHEC) in food-producing animals is a viable strategy to minimize human disease initiated by exposure to these microorganisms. To this end, an intervention strategy involving the electrostatic hybridization of two commonly used anti-infective agents for veterinary practice (i.e. chlorhexidine and ampicillin) was evaluated to curtail EHEC-transmitted disease from ruminant sources. Chlorhexidine di-ampicillin is a novel group of uniform material based on organic salts (GUMBOS) with inherent in vitro antibacterial activity that comes from its parent antimicrobial ions, chlorhexidine and ampicillin. METHODS: Antibacterial activities for chlorhexidine diacetate, sodium ampicillin, chlorhexidine di-ampicillin and stoichiometrically equivalent 1 : 2 chlorhexidine diacetate : sodium ampicillin were assessed using the serial 2-fold dilution method and time-kill studies against seven isolates of E. coli O157:H7 and one non-pathogenic E. coli 25922. Further studies to investigate synergistic interactions of reacted and stoichiometrically equivalent unreacted antimicrobial agents at MICs and possible mechanisms were also investigated. RESULTS: Synergism and in vitro antibacterial activities against EHEC were observed in this study, which suggests chlorhexidine di-ampicillin could be a useful reagent in reducing EHEC transmission and minimizing EHEC-associated infections. Likewise, chlorhexidine di-ampicillin reduced HeLa cell toxicity as compared with chlorhexidine diacetate or the stoichiometric combination of antimicrobial agents. Further results suggest that the mechanisms of action of chlorhexidine di-ampicillin and chlorhexidine diacetate against E. coli O157:H7 are similar. CONCLUSIONS: Reacting antimicrobial GUMBOS as indicated in this study may enhance the approach to current combination drug therapeutic strategies for EHEC disease control and prevention.


Subject(s)
Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Chlorhexidine/therapeutic use , Disinfectants/therapeutic use , Escherichia coli Infections/prevention & control , Escherichia coli O157 , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Cell Survival/drug effects , Drug Combinations , Drug Synergism , Drug Therapy, Combination , Food Microbiology , HeLa Cells , Humans , Indicator Dilution Techniques , Kinetics , Microbial Sensitivity Tests , Salts , Shiga Toxin/metabolism , Shiga-Toxigenic Escherichia coli/metabolism
2.
Chem Biol Drug Des ; 78(1): 33-41, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21443681

ABSTRACT

We herein report the preparation and investigation of antibacterial activity of biocidal ionic liquids (ILs) consisting of cationic imidazolium or pyridinium and an anionic ß-lactam antibiotic. The antibacterial properties were quantified by measuring the minimum inhibitory concentration and minimum bactericidal concentration against Escherichia coli O157:H7, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium. In general, the ILs had improved antibacterial activity than their parent materials, whether individually or in combination. In 83% of the experiments, the ampicillin ILs (Amp-ILs) had better antibacterial activities than their quaternary halide parent materials, whereas in 92% of the experiments, Amp-ILs outperformed the commercially available sodium ampicillin salt. Amp-ILs had up to 43 times improved antibacterial activity than sodium ampicillin. Overall, when normalized for ampicillin content, ILs had greater antimicrobial activity against E. coli O157:H7, K. pneumoniae, S. aureus, and E. faecium than sodium ampicillin alone.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Drug Design , Drug Evaluation, Preclinical , Imidazoles/chemistry , Pyridinium Compounds/chemistry , beta-Lactams/chemical synthesis , beta-Lactams/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Inhibitory Concentration 50 , Ions , Magnetic Resonance Spectroscopy , Micelles , Microbial Sensitivity Tests , Solubility
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