Viruses stop antibiotic-resistant bacteria

Nearly a century ago, biologists discovered viruses that prey upon bacteria. When penicillin and other antibiotics emerged a few decades later, however, physicians largely abandoned their efforts to use these bacteriophages, or phages, to thwart infectious diseases.

As more bacteria develop resistance to antibiotics, there’s renewed interest in phages (SN: 6/3/00, p. 358: Viruses that slay bacteria draw new interest). Scientists now report that these viruses can prevent mice from dying after being infected with an antibiotic-resistant bacterium.

“This is the first published study of phages working against multidrug-resistant bacterial strains,” says study coauthor Richard Carlton of Exponential Biotherapies in Port Washington, N.Y.

While phages are a popular therapy among physicians in the former Soviet Union, most U.S. investigators have remained skeptical. Few scientifically rigorous studies support phages’ effectiveness. Also, side effects from contaminants have plagued phage therapy since its inception.

In the 1990s, concerned about the rise of antibiotic-resistant bacteria, Carl R. Merril of the National Institutes of Health in Bethesda, Md., and his colleagues began to use modern scientific tools to improve phage therapy (SN: 6/1/96, p. 350). For example, the group developed a method to isolate phages that persist in an animal’s blood longer than most do. In one study, such phages protected mice injected with lethal quantities of the bacterium Escherichia coli.

Merril’s team then joined forces with Carlton’s company to investigate applying phages to fight antibiotic-resistant strains of enteroccoci, particularly ones impervious to the drug vancomycin. More than 10 percent of the infections acquired by patients in hospitals now result from vancomycin-resistant enterococci.

These gut bacteria pose a major health risk to people with weakened immune systems and serve as a reservoir of antibiotic-resistant genes that more-dangerous germs can draw upon. For example, reports of vancomycin-resistant Stapholococcus aureus infections have recently alarmed physicians.

In the January Infection and Immunity, Merril, Carlton, and their colleagues report successfully using phages to defend mice against a strain of Enterococcus faecium that resists vancomycin and other antibiotics. The researchers inoculated rodents with the bacterium and 45 minutes later injected some animals with phages that target the germ.

Untreated animals died within 2 days. Depending on the dose, 40 percent or more of the mice receiving the phages overcame the infection and survived.

“At the right dose, we get 100 percent survival,” says Carlton.

Even when the researchers delayed treatment for a day, until the infected mice were very sick, the phages saved about 50 percent of them, notes Merril. There were no harmful side effects to the treatment, say the researchers.

“This is very important and significant work, mainly because we need [animal] studies that are proof of principle,” says Marissa Miller of the National Institute of Allergy and Infectious Disease in Bethesda, Md. “This is a huge step.”

Exponential Biotherapies has begun testing in people one of the phages used in the mouse study. In a test tube, the phage kills about 95 percent of the E. faecium strains seen in hospitals, says Carlton.

Last year, the company gave multiple injections of the phage to healthy volunteers and discovered no side effects. The firm now plans a multihospital trial of the phage’s effectiveness in people with enterococci infections.

While two drugs that work against vancomycin-resistant enterococci have recently received approval for use in the United States, some strains have already developed resistance to these new antibiotics. Carlton suggests that combining phage therapy with the drugs may prolong their usefulness.