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Silver Improves Antibiotic Performance Against Bacteria

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Researchers at Harvard University and Boston University found adding a silver compound to several types of antibiotics improved their performance against a range of bacterial infections in lab and animal tests. The team led by James Collins, a faculty member at both institutions, published its findings in this week’s issue of the journal Science Translational Medicine (paid subscription required).

Silver, the authors note, has been used as an antibacterial agent since ancient times, but the way it worked against bacteria was not understood. The researchers tested a silver nitrate salt on normal and mutant strains of E. coli bacteria. They also evaluated the adding of silver nitrate to several antibiotics as a treatment for infections in mice, on dormant residual bacteria that sometimes survive antibiotic treatments, and with bacterial colonies called biofilms that collect and spread on hospital surfaces or in the body.

The tests with E. coli found the silver compound helped produce more reactive oxygen species, molecules that damage the membrane surrounding the bacterial cells, as well as upsetting the cells’ metabolic processes and damaging their DNA. When added to three common antibiotics — gentamycin, ofloxacin, and ampicillin — small amounts of silver made E. coli from 10 to 1,000 times more sensitive to the drugs.

The Harvard-Boston team added silver compounds to common antibiotics to test on mice with E. coli urinary infections and peritonitis, an infection of the membrane that lines the inner layer of the abdominal wall. The addition of silver nitrate to gentamicin reduced urinary tract infection cell counts fourfold compared to gentamicin alone.

Adding silver nitrate to vancomycin resulted in a 100-fold decrease in peritonitis cells, while the drug or silver nitrate alone had no effect on the infection. The vancomycin-plus-silver combination also increased the survival rate of the mice after five days, compared to vancomycin or silver alone.

The researchers found another benefit of silver in these tests: the addition of silver helped make vancomycin effective against Gram-negative bacteria, such as those found in food poisoning and some hospital-acquired infections. Vancomycin is normally considered effective in killing Gram-positive bacteria, such as Staphylococcus and Streptococcus.

In lab tests, the team tested the silver nitrate compound on E. coli persisters, the dormant residual bacteria that sometimes survive antibacterial treatments, and biofilm colonies of bacteria that can spread over surfaces in the body or in health care facilities. The results showed the combination of silver and antibiotics — ampicillin, ofloxacin, and gentamicin — more effective against the persister cells than the silver compound or antibiotics alone. Likewise, the combination of gentamicin and silver compound killed more biofilm cells than the antibiotic or silver treatments alone.

In the tests with mice, the researchers tested the potential toxicity of the silver nitrate at various levels to determine the amounts effective against bacteria, when added to antibiotics, yet still not be harmful to the mice. The results showed small amounts of silver could increase the power of antibiotics without harming the mice. The added silver likewise did not harm cultured human cells, which suggests silver in a pill or injected form could be safe for humans as well.

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