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Altered Bacteriophages May Curb Hospital MRSA


 

LISBON — MRSA, you may have met your match.

Immobilized bacteriophages offer a novel solution to the relentlessly growing problem of hospital-acquired infection with methicillin-resistant Staphylococcus aureus, Michael Mattey, Ph.D., said at the 12th International Congress on Infectious Diseases.

Bacteriophages are highly effective bacteria killers. Until recently, however, their use in medical settings has been impractical because in nature these viruses are effective only in water.

That hurdle has now been overcome. A British biotech company, Blaze Venture Technologies, has developed a stabilized bacteriophage that's immobilized on cosmetic-grade, 10-micrometer nylon beads. These are naturally occurring bacteriophage isolates selective for MRSA that have been altered so they can withstand dehydration.

When a powder of the microscopic phage-coated beads is poured into standard medical cleaning products used to wipe down hospital surfaces, MRSA is killed on contact. Better yet, after the cleanser has dried, the phages left behind remain active for 2 weeks at room temperature, preventing reintroduction of MRSA on treated wards, explained Dr. Mattey, a Blaze employee who also is at the University of Strathclyde, Glasgow, which holds a general patent on bacteriophage-immobilization technology.

Current approaches to the MRSA problem entail treating infected patients with drugs to which the bacteria remain sensitive. That applies pressure to breed further resistance, with eventual loss of antibiotic effectiveness. In contrast, the strategy underlying immobilized bacteriophages involves reversal of antibiotic resistance through selective control aimed at taking away the MRSA strains' evolutionary advantage.

“Really, the whole idea is, 'Let's breed better bacteria,'” he said in an interview. The prevalence of MRSA among S. aureus strains is increasing at about 3.5% annually in hospitals in the United States and Europe.

“So if you got rid of 3.5% of the [bacterial] parents with MRSA, you would stabilize things. And if you got rid of more than 3.5%, you'd reverse the MRSA problem,” Dr. Mattey said at the meeting sponsored by the International Society for Infectious Diseases. Indeed, mathematical models indicate that with a 6% annual kill rate of MRSA, the prevalence of resistant strains would drop from 60% to essentially zero in a 25-year period.

Immobilized MRSA-hunting bacteriophages are attractive not only as an additive for cleaning solutions, but also for hand cleansers, impregnated wipes, and sprays. The Blaze cleaning products are currently undergoing testing to establish their safety. Dr. Mattey expects European agency approval for use in hospitals in 2–3 years.

MRSA will be the initial target of the bacteriophage-enhanced medical cleaning products simply because MRSA is such an important problem. But bacteriophage isolates selective for virtually any antibiotic-resistant bacteria can be developed. And it takes only about 36 hours to culture bacteriophages that will counter new mutant MRSA strains—versus a decade to develop a new antibiotic.

Blaze initially is moving into the medical cleaning market because of the pressing need coupled with the fact that the regulatory bar is set relatively low, with only a demonstration of product safety required. But company scientists have other irons in the fire.

The same phage technology has been used to develop a 10-minute MRSA-screening device as an alternative to conventional MRSA testing, which requires culturing patient swabs for several days. Early detection and containment of MRSA outbreaks has the potential to dramatically reduce nosocomial infection rates. The company is gearing up for field trials of the point-of-care device through two U.K. National Health Service trusts.

In addition to MRSA, the sensor can be used to detect a wide range of other problem bacteria by using cards coated with bacteriophages selective for that particular organism.

Blaze also is developing therapeutic applications for the stabilized bacteriophages. Surgical suture material impregnated with immobilized phage has been “very successful” at preventing serious wound infections in animal studies, according to Dr. Mattey.

In addition, Blaze scientists have conducted positive proof-of-concept animal studies involving injection of phage-bearing 5-micrometer nylon beads for treatment of septicemia.

“In human studies, we won't be injecting nylon beads. We'll use the sort of polymers used in biodegradable sutures that break down in a week or two,” the biologist said.

Wiping down hospital surfaces with cleaning solutions that contain phage-coated beads kills MRSA on contact. DR. MATTEY

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