Recycling Antibiotics into GUMBOS: A New Combination Strategy to Combat Multi-Drug-Resistant Bacteria

Molecules

Marsha R. Cole²  Jeffery A. Hobden³  Isiah M. Warner¹ 

[1] Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA;Commodity Utilization, Southern Regional Research Center, Agricultural Research Services, United States Department of Agriculture, New Orleans, LA 70124, USA;Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans, LA 70112, USA

关键词: chlorhexidine;    β-lactam antibiotic;    multi-drug resistant;    GUMBOS;    combination drug therapy;    ion pair;    antibacterial;    synergy;   

DOI  :  10.3390/molecules20046466

来源: mdpi

【 摘 要 】

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 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.