Navy Medicine Researchers Develop Therapeutic Cocktail of Environmental Phages to Overcome Antibiotic-Resistant Infection

By Doris Ryan
Naval Medical Research Center Public Affairs

In a proof-of-concept study, a team from the Naval Medical Research Center (NMRC), in collaboration with the Walter Reed Army Institute of Research (WRAIR), reported success in combating an antibiotic-resistant infection in a laboratory model using bacteriophage therapy.

The results will be published in the October issue of the journal, “Antimicrobial Agents and Chemotherapy.” The paper, “Personalized Therapeutic Cocktail of Wild Environmental Phages Rescues Mice From A. Baumannii Wound Infections,” is available online on the American Society for Microbiology website http://aac.asm.org/content/early/2016/07/13/AAC.02877-15.full.pdf+html/.

Acinetobacter baumannii is recognized as one of the most difficult antimicrobial-resistant gram-negative infections to treat. Combat-related injuries are at high risk for serious infections. Infections have occurred in up to 35 percent of service members who have had combat-related injuries during Operations Iraqi and Enduring Freedom. Those infections are often very hard to treat because of multidrug antibiotic resistance in the bacteria present in the wound.

NMRC worked in collaboration with Navy Medicine’s overseas laboratories to collect phages from environmental sources around the world. Using the collection of phages, referred to as a phage library, personalized phage cocktails could be made by selecting multiple individual phages from the phage library to create phage mixes customized to the needs of each patient.

Cmdr. Michael Stockelman, deputy director of the Infectious Diseases Directorate at the Naval Medical Research Center, shows petri dishes containing pathogens used in phage research. The Naval Medical Research Center, in collaboration with the Walter Reed Army Institute of Research, successfully combated an antibiotic-resistant infection in a laboratory model through bacteriophage therapy, which uses viruses found in the environment that are known for their activity against bacteria. (Photo by NMRC Public Affairs)

Cmdr. Michael Stockelman, deputy director of the Infectious Diseases Directorate at the Naval Medical Research Center, shows petri dishes containing pathogens used in phage research. The Naval Medical Research Center, in collaboration with the Walter Reed Army
Institute of Research, successfully combated an antibiotic-resistant infection in a laboratory model through bacteriophage therapy, which uses viruses found in the environment that are known for their activity against bacteria. (Photo by NMRC Public Affairs)

NMRC also worked closely with WRAIR’s Wound Infections Department to test the phage cocktails in wound infection models and demonstrate that personalized phage cocktails can treat infections.

“Bacteriophages, commonly known as phages, are viruses found in the environment, and are known for their activity against bacteria; this is why they have therapeutic potential, and may be able to treat bacterial infections even when antibiotics fail,” said Cmdr. Michael Stockelman, deputy director of the NMRC Infectious Diseases Directorate. “In this study we showed that a phage cocktail can be designed and used to target an infection caused by antibiotic-resistant bacteria in a wound infection experimental model.”

Phages have an entirely different way of attacking bacteria compared to the mechanism of action for conventional antibiotics. Phages invade the bacterial cells, replicate in the cells, and destroy the cells when they rupture and release more phages into the body. Because phages multiply when they kill the disease-causing bacteria, the phage treatment actually gets stronger where it is needed most, at the infection site. In addition, phages do not affect bacteria that are not being targeted.

“Our bodies have many different kinds of bacteria that normally live on or in us, and they help our bodies work,” said Stockelman. “When we take antibiotics, we impact the whole system, killing good bacteria along with the bad bacteria. Phages will not damage that community of bacteria called the microbiome the way antibiotics do.”

Stockelman explained phage therapy could allow physicians to treat and manage wound infections in combat casualties who would otherwise need repeated surgeries or other extreme measures, including limb amputations, to control the infections. Successful phage therapy would greatly improve the quality of life for wounded warriors and make it more likely wound infections would not prevent a warfighter’s ability to return to duty.

The next step for the team is to plan for clinical trials testing phage cocktails in human volunteers. Initial studies will confirm phage is safe in humans. For future clinical trials, researchers hope to work with treating physicians to eventually make personalized phage cocktails for patients with otherwise untreatable infections, to test the ability of phage therapy to overcome antibiotic resistance in a medical setting, outside the laboratory.

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