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Scientists Say New Antibacterial Approach Could Resolve Serious Skin Infections

Liquid salts disrupt bacterial biofilms

Like a protective tent over a colony of harmful bacteria, biofilms make the treatment of skin infections especially difficult. Microorganisms protected in a biofilm pose a significant health risk because of their antibiotic resistance and recalcitrance to treatment. Biofilm-protected bacteria account for approximately 80% of total bacterial infections in humans and are 50 to 1,000 times more resistant to antibiotics compared with simpler bacterial infections.

“In essence, we may have stumbled onto a magic bullet,” said Dr. David Fox, a researcher at the Los Alamos National Laboratory. “Through a robust screening strategy, our research team has identified a unique class of materials, known as ionic liquids [liquid salts], which both neutralize biofilm-forming pathogens and deliver drugs through the skin.”

“In several cases, we found that the ionic liquid was more efficacious on a biofilm than a standard bleach treatment and exhibited minimal cytotoxicity effects on human cell lines (unlike bleach),” Fox added. “This has excellent prospects for aiding antibiotic delivery to the pathogen through biofilm disruption, but most interestingly, the ionic liquids themselves are quite effective for pathogen neutralization.”

Biofilms often persist in the periphery of a wound, beneath an intact, healthy skin layer, and the difficulty of their treatment is largely due to the outermost layer of the skin, the stratum corneum, being a natural barrier for drug delivery.

“If the bacterial biofilm can be disrupted, delivery of antibiotics is greatly enhanced, and any dispersed pathogens are generally restored to normal antibiotic susceptibility,” Fox said. “Further, many bacterial infestations in wounds penetrate under the outer skin layer, the stratum corneum, and deep into the tissue (epidermis and dermis). These materials are able to penetrate through the skin and effectively carry antibiotics to the deepest layers.”

In an article published in the Proceedings of the National Academy of Sciences, the researchers identified ionic liquids that could effectively disrupt biofilms, neutralize pathogens, and enhance the delivery of antibiotics into skin. One liquid in particular — choline geranate — showed excellent antimicrobial activity, minimal toxicity to epithelial cells and skin, and effective permeation enhancement for drug delivery. Specifically, choline geranate was comparable with, or more effective than, bleach against established biofilms of Salmonella enterica and Pseudomonas aeruginosa, respectively. In addition, choline geranate increased the delivery of the antibiotic cefadroxil by more than 16-fold into the deep-tissue layers of the skin without inducing skin irritation.

Biofilms are a major cause of chronic wounds and wound degeneration. Wounds from infected surgical incisions result in 1 million additional hospital days. Additional causes of bacteria-infected wounds include traumatic injuries, diabetic foot ulcers, venous leg ulcers, and pressure ulcers.

The total economic burden of skin disease was estimated to be approximately $96 billion in 2004, and the prevalence of and health care costs for skin disease have been increasing over the last three decades. Bacterial infections in the skin are among the most common diagnoses in hospital patients, accounting for about 10% of all hospital visits. Staphylococcus aureus infections acquired in hospitals, which account for only 16% of nosocomial infections, are estimated to be responsible for $9.5 billion in extra patient costs and 12,000 deaths annually.

Source: Los Alamos National Laboratory; August 26, 2014.

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