We herein report the preparation and investigation of antibacterial activity of biocidal ionic liquids (ILs) consisting of cationic imidazolium or pyridinium and an anionic β-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.

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Abstract:The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin) and a well-known antiseptic (chlorhexidine di-acetate) were fashioned into a group of uniform materials based on organic salts (GUMBOS) as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics), GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell OPEN ACCESSMolecules 2015, 20 6467 types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria.

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