A new study led by a research team from the Massachusetts Eye and Ear Medical School at Harvard Medical School describes how bacteria are adapted to modern hospital environments and are continuously causing antibiotic-resistant infections. Infections acquired by hospitalized patients are more likely to be antibiotic-resistant than those occurring elsewhere, and hospitals are making significant efforts to prevent them. Despite the best efforts, some bacteria can continue and circulate among patients, causing repeated infections. This study examined one of the first in-hospital epidemics of a multi-resistant bacterium, Enterococcus faecalis, which occurred from the early mid-1980s, causing over 60 types of epidemics.
The study, published on April 10 at Science translational medicine, was led by a research team headed by Michael Gilmore, MD, senior eye and ear, and professor of ophthalmology Sir William Osler, and director of the Institute of Infectious Diseases at the Department of Ophthalmology at the Harvard Medical School. The team compared DNA sequences of bacteria that had been archived since the appearance 30 years ago by collaborator Mark M. Huikke, MD, a contagious disease specialist, who is now at the Oklahoma University's Center for Health Sciences. The researchers identified mutations in bacteria as they caused one infection after another, over 4 years, with the help of Gilmore research associates, Daria Van Thien, Dr. Daria Van Thane.
The authors of the study hope that findings from new information on how enterococci will infect the bloodstream will help scientists and doctors develop new ways to prevent these infections from occurring and be better treated when they occur.
"Knowing how the microbes exceed the immune system of the body and antibiotics tells us what's crucial for the microbes to cause infection," says Dr. Gilmore. "This in turn gives us a clearer picture of new goals for the development of the next generation of antibiotics and for targeting careful use in and out of hospitals."
Naturally occurring in the human stomach, enterococci bacteria can lead to infections, including blood and urinary tract infections, surgical site infections, and endocarditis – cardiac valve infection.
The researchers examined bacteria genomes to analyze samples from the onset of bacteremia in patients in a hospital in Wisconsin between 1984 and 1988 who were caused by drug-resistant Enterococcus faecalis in order to learn how to adapt to the existence in the hospital and the transfer from one patient to another. By returning to the first days of the antibiotic resistance problem, Dr. Van Thane, Dr. Gilmore and his colleagues saw it Enterococcus faecalis entering the bloodstream first turned into an unusual path that allows the microbe to create a new substance that helps strengthen its cell wall. This makes the bacteria more capable of resisting killing by white blood cells, as well as from the penicillin-class antibiotic attacking the bacterial cell wall. The authors also noted that in the middle of the phenomenon, the types of adaptations suddenly changed, and the bacteria began to strengthen their cell walls in a new way. This change corresponds to the introduction and widespread use of a new antibiotic called imipenem.
Dr. Van Thine, now an assistant at the Department of Medicine at the University of Pittsburgh, was able to recreate the exact change 30 years later in the laboratory using an antibiotic of imipenem, proving the relationship.
"Our study shows how an enterococcal epidemic arose and developed over the extended hospitality phenomenon and how the epidemic of the epidemic responded to the immune selection of the host and change the regimens of antibiotics," said Dr. Van Thane. "These findings highlight new pathways that can be further used in the future to control and manage enterococcus infections acquired in a hospital."
Antibiotic-resistant infection is a leading public health threat worldwide. It is estimated that by 2050, more people could die from infections that are no longer treated with antibiotics, rather than from cancer. Understanding how some bacteria have managed to overcome our natural immune defense and new drugs as introduced is the key to preventing a future where up to 10 million people may die of antibiotic-resistant infection each year, according to Dr. Gilmore.
"This research study is a powerful example of how scientists such as Dr. Gilmore use new genetic technologies and molecular biology to discover new and important information about drug-resistant bacteria so that we can better understand and finally prevent and we are treating dangerous life-threatening infections, says Dr. Joan W. Miller, professor David Glennning Kogan and president of ophthalmology at Harvard Medical School, Chief of Ophthalmology at the Massachusetts General Hospital and Massachusetts and Chief Ophthalmologist at Bree women's and women's hospital.
In addition to Dr. Gilmore and Dr. Van Thine, co-authors of the Science translational medicine The study includes Dr. Agidel L. Manson and Dr. Ashley M. Earl, MD. Shirn Institute, Dr. Mark M. Hookeeke, Oklahoma Health Sciences Center, and Dr John Caranacols from the Chuck Chase Center for Cancer. This study was supported by PHS grants. AI083214 (Harvard Program for Antibiotic Resistance) and AI072360 to M.S.G. and grant no. EY028222 to D.V.T. Additional support for subsequent genome assay was provided by NIAID contract no. HHSN272200900018C and grant no. U19AI110818 to the Wide Institute. М.М.Х. was supported by the Francis Duffy Foundation.
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About the Department of Ophthalmology at Harvard University
The Department of Ophthalmology of Medicine at Harvard (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the state. More than 400 full-time faculty and apprentices work in eight Harvard Ophthalmology Branches, including Massachusetts's eye and ear [home to Schepens Eye Research Institute], Massachusetts General Hospital, Brigham and Women's Hospital, Boston Children's Hospital, Beth Israel Diabetes Center, Jolin Diabetes Center, Botanic Environment Institute, Boston Health System, and the Cambridge Health Alliance. Formally established in 1871, the department was built on a strong and rich foundation for medical education, research and clinical care. Over the years, faculty and alumni have a profound influence on ophthalmic science, medicine and literature – helping to transform the field of ophthalmology from the branch of surgery to an independent medical specialty in the forefront of science.