Bacterial spores in capsules taken by mouth can prevent recurrent C. difficile infection, results from a preliminary study suggest.
Clostridium difficile is the most common hospital-acquired infection in the United States and can cause persistent, sometimes life-threatening diarrhea. Fecal microbiota transplant has shown promise in many clinical studies as a treatment for C. difficile, but uncertainty has surrounded how such transplants should be regulated and standardized. Also, the still-investigational procedure is oftenÂ performed byÂ colonoscopy, which may be difficult forÂ some patients to tolerate.
The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.
Kraft and Tanvi Dhere, MD, assistant professor of medicine (digestive diseases) have led development of the fecal microbiota transplant program at Emory. They are authors on the capsule study, along with investigators from Mayo Clinic, Massachusetts General Hospital, Miriam Hospital (Rhode Island), and Seres Therapeutics, the study sponsor.
While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more
In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found.Â One oxygen-shy type of bacteria that grows in the wound-healing environment,Â Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal andÂ human obesity.
An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.
The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.
The results were published on January 27 inÂ Nature Microbiology.Â Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.
â€œThis is a situation resembling recovery after a forest fire,â€ says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. â€œOnce the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.â€ Read more
One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics withÂ non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.
As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrhealÂ Immodium, can make bacteria sensitive toÂ tetracycline-type antibiotics.
Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.
“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.
Medical ethnobotanist Cassandra Quave collecting plant specimens in Italy
Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. SheÂ and her colleagues have been investigatingÂ compounds that can disruptÂ biofilms, thusÂ enhancingÂ antibiotic activity. More at eScienceCommonsÂ and at her lab’s site.
Part of the problem of antibiotic resistanceÂ involves physiciansâ€™ habits. Doctors are used to prescribing antibiotics in certain situations, even when they may be inappropriate or when alternatives may be best. However, they may be susceptible to â€œnudgesâ€, even if health care organization policies donâ€™t formally restrict their choices. Former White House regulatory policy guru Cass Sunstein has written several books on this concept.
In March 2015, MD/PhD student Kira Newman and colleagues published a studyÂ in Journal of General Internal Medicine that has some bearing on this idea, althoughÂ it doesnâ€™t address antibiotic resistance directly:
Yelp for Prescribers: a Quasi-Experimental Study of Providing Antibiotic Cost Data and Prescription of High-Cost Antibiotics in an Academic and Tertiary Care Hospital.
The authors describe a shift involving the Emory University hospital electronic health record and order entry system. When a patient has systemic or urinary tract bacterial infection, the system shows a table of antibiotic sensitivity data alongside blood or urine culture results.
Beginning in May 2010, cost category data for antibiotics were added. Explicit numbers were not included â€“ too complicated. Instead, the information was coded in terms of $ to $$$$. For the year after the change, the authors report a 31 percent reduction in average cost per unit of antibiotics prescribed. Read more
Evolutionary theory says mutations are blind and occur randomly. But in theÂ controversialÂ phenomenon of adaptive mutation, cells can peek under the blindfold, increasing their mutation rate in response to stress.
Scientists at Winship Cancer Institute, Emory University have observed that an apparent “back channel” for genetic information called retromutagenesis can encourage adaptive mutation to take place in bacteria.
The results were published Tuesday, August 25 inÂ PLOS Genetics.
“This mechanism may explain how bacteria develop resistance to some types of antibiotics under selective pressure, as well as how mutations in cancer cells enable their growth or resistance to chemotherapy drugs,” says senior author Paul Doetsch, PhD.
Doetsch is professor of biochemistry, radiation oncology and hematology and medical oncology at Emory University School of Medicine and associate director of basic research at Winship Cancer Institute. The first author of the paper is Genetics and Molecular Biology graduate student Jordan Morreall, PhD, who defended his thesis in April.
Retromutagenesis resolves the puzzle: if cells arenâ€™t growing because theyâ€™re under stress, which means their DNA isnâ€™t being copied, how do the new mutants appear?
The answer: a mutation appears in the RNA first. Read more