Before antibiotics were invented, people often used silver, a known antimicrobial that can also be toxic, to tackle infections.

Researchers in the early 1900s also noticed a mysterious and inconsistent effect from using a mild electric current to kill nasty microbes.

Both methods were problematic, though, and were quickly abandoned with the advent of antibiotics, which killed bacteria so effectively throughout the twentieth century.

Now, as the efficacy of conventional antibiotics wanes, Washington State University researchers are reinventing old ideas to fight bacterial infection.

At their lab in the School of Mechanical and Materials Engineering, Amit Bandyopadhyay and Susmita Bose have developed a nontoxic way to use tiny amounts of silver to control difficult-to-treat bacterial infections that often occur after orthopedic surgery.

The researchers were able to control infection by carefully affixing nanosized specks of silver onto stainless steel bone implant materials. When they added a nasty and common Staphylococcus aureus bacterial infection, the silver-coated implants successfully fought off the infection for as long as nine months—much longer than one could use prophylactic antibiotics. The research, funded by the National Institutes of Health, found that the miniscule number of silver ions that escaped into surrounding tissues did not have any toxic effects.

The engineers also incorporated silver into calcium phosphate ceramics, bone-like materials that are commonly used in jaw and dental surgeries. They were able to slowly release tiny, nontoxic amounts of silver at levels that would be effective for killing bacteria.

“The challenge is to control the release amount and the rate of release,” says Bose. “You need to release a small amount to be effective, but not beyond toxicity.”

Meanwhile, another WSU research group is tackling and beating drug-resistant bacterial infections in chronic wounds with another old idea—using a low electric current.

Researchers have tried electrical stimulation as a method to kill bacteria for more than a century, but, with only a poor understanding of how it worked, they had limited success.

Haluk Beyenal, the Paul Hohenschuh Distinguished Professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering, and his team determined how to better use an electric current to produce a disinfectant—hydrogen peroxide. They carefully control the current to assure a specific electrochemical reaction at an exact rate.

With improved understanding of the reaction, the researchers developed an “e-scaffold,” a sort of electronic bandage made of conductive carbon fabric. With the addition of an antibiotic, the researchers used the e-scaffold to tackle difficult-to-treat “persister cells” that hide in bacterial slime layers known as biofilms. These subpopulations of cells often survive treatment, grow, and multiply, resulting in chronic infections.

“I didn’t expect to kill persister cells using the e-scaffold,” says Beyenal. “To verify these unexpected results, we biologically replicated the work multiple times.”

The e-scaffold created an electrical current that produced a low and constant concentration of hydrogen peroxide, which disrupted the biofilm matrix and damaged bacteria cell walls and DNA, allowing for effective antibiotic penetration. Their method does not damage surrounding tissue, and the bacteria are unable to develop resistance.

“It turns out that hydrogen peroxide is really hard on biofilms,” says Doug Call, an epidemiologist in the Paul G. Allen School for Global Animal Health who is involved in the work.

With their e-scaffold prototype, the researchers were able to kill all of the highly persistent Pseudomonas aeruginosa PAO1 bacteria in their samples.