Silver Gives New Life to Overprescribed and Ineffective Antibiotics

Low doses of silver can enhance the germ-fighting abilities of antibiotic drugs, even those drugs that have become less effective after decades of overprescribing has caused some microbes to become resistant, according to a team of researchers led by Jim Collins of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

They showed that not only does the addition of silver make some antibiotic drugs up to 1,000 times more effective, but silver has also made at least one drug-resistant bacterium surrender to antibiotics once again. In addition, silver has allowed the expansion of at least one drug, Vancomycin, an antibiotic that is usually only effective at killing Gram-positive bacteria such as Staph and Strep. With the addition of silver, it can also kill Gram-negative bacteria such as those that cause food poisoning (like E. coli) and hospital-acquired infections.

The researchers also learned that the addition of silver helps dispatch two kinds of microbes that are tough to knock down with antibiotics. The first are microbes caused by sticky biofilms, such as those that cling to catheters and other medical devices. This is why many catheters are coated by silver. The second are bacteria that initially seem to have been killed by antibiotics, only to resurface after discontinued use of the medicine. This is one reason why antibiotic labels warn patients to ‘finish all drugs’ and why
some infections, like those in the urinary tract, can be especially tough to fight. In one test by Collins’ team, a mouse with a urinary tract infection from E. coli was resistant to tetracycline until silver was added.

Although previous studies have shown the mechanism by which silver attacks germ cells – it destroys the cell walls – these researchers have gone a step further. By studying silver’s interaction with E. coli they determined that the metal stimulated the target bacteria to produce more reactive oxygen species (ROS), which are chemicals produced
by living cells during the process of metabolism. ROS are beneficial to cells in the right amount but at higher levels they can damage proteins and DNA. They can also breach
the cell’s membrane, which is one line of defense that cells use against intruders like beneficial drugs.

In effect, silver can be thought of as a battering ram that punches a hole in a cell’s wall, which then allows antibiotic drugs to enter and kill the bacteria cell itself. The Harvard research also showed that even small doses of widely-used antibiotics such as gentamycin, ofloxacin, and ampicillin were up to 1,000 times more effective when combined with silver to fight E. coli.

In still another test at Harvard, mice with peritonitis, an inflammation of tissues in the abdomen – a life- threatening condition seen in humans – were given silver in
conjunction with vancomycin. Ninety percent of mice treated in this manner lived. In control tests, 90 percent of those treated only with the drug died. The team also tested whether silver was toxic to subjects and found that the amounts necessary to enhance the antibiotics were so low as not to harm mice or human cells.

Collins noted: “We’re keen to explore how smart drug-delivery nanotechnologies being developed at the Wyss could help deliver effective but nontoxic levels of silver to
sites of infection.” Added Don Ingber, M.D., Ph.D., Wyss Institute Founding Director: “Doctors desperately need new strategies to fight antibiotic-resistant infections, and Jim [Collins] and his team have uncovered one that’s incredibly versatile, and that could be put to use quickly in humans.”

The study, which appeared June 19th in the journal Science Translational Medicine, was supported by funds from the National Institutes of Health, Howard Hughes Medical Institute and the Wyss Institute.

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