title: Minimizing human infection from Escherichia coli O157:H7 using GUMBOS.
abstract: OBJECTIVE
  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.
authors: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
authors: Marsha R
authors: MR
authors: Cole
authors: Min
authors: M
authors: Li
authors: Ravirajsinh
authors: R
authors: Jadeja
authors: Bilal
authors: B
authors: El-Zahab
authors: Daniel
authors: D
authors: Hayes
authors: Jeffery A
authors: JA
authors: Hobden
authors: Marlene E
authors: ME
authors: Janes
authors: Isiah M
authors: IM
authors: Warner
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000627:therapeutic use*; D004202:Disinfectants / Q000627:therapeutic use*; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000517:prevention & control*; D019453:Escherichia coli O157; D005516:Food Microbiology; D006367:HeLa Cells; D006801:Humans; D007201:Indicator Dilution Techniques; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D012492:Salts; D022621:Shiga Toxin / Q000378:metabolism; D054323:Shiga-Toxigenic Escherichia coli / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004202:Disinfectants; D004338:Drug Combinations; D012492:Salts; D022621:Shiga Toxin; D000667:Ampicillin; D002710:Chlorhexidine
keywords: ampicillin; antibacterial activity; chlorhexidine; combination drug therapy