Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy.
The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more
When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.
In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.
C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.
At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.
Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more
If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.
A diagnostic test used by hospitals says a recently isolated strain of bacteria is susceptible to the “last resort” antibiotic colistin. But the strain actually ignores treatment with colistin, causing lethal infections in animals.
Through heteroresistance, a genetically identical subpopulation of antibiotic-resistant bacteria can lurk within a crowd of antibiotic-susceptible bacteria. The phenomenon could be causing unexplained treatment failures in the clinic and highlights the need for more sensitive diagnostic tests, researchers say.
“Heteroresistance has been observed previously and its clinical relevance debated,” Weiss says. “We were able to show that it makes a difference in an animal model of infection, and is likely to contribute to antibiotic treatment failures in humans.”
Weiss is director of the Emory Antibiotic Resistance Center and associate professor of medicine (infectious diseases) at Emory University School of Medicine and Emory Vaccine Center. His laboratory is based at Yerkes National Primate Research Center. The co-first authors of the paper are graduate students Victor Band and Emily Crispell.
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.
Emory is preparing to launch a center devoted to antibiotic resistance. On Wednesday, Arjun Srinivasan, one of the CDCâ€™s point people for antibiotic use and hospital acquired infections, kicked off the preparations with a talk on the multifaceted nature of this problem.
Without attempting to cover everything related to antibiotic resistance (that would take a bookÂ — or several), I willÂ note in an upcoming post how Emory and partners such asÂ Childrenâ€™s Healthcare of Atlanta already haveÂ begun assembling many of the necessary tools.
Tackling antibiotic resistance has to take into account the habits of physicians, the expectations of patient, improved surveillance and antibiotic overuse in agriculture, as well as research on new antibiotics and detecting dangerous bacteria. In short, itâ€™s both a science and policy issue — captured well by the documentary Resistance.
At the end of his talk, Srinivasan made a remark that brought this home for me, saying â€œWe just have to push all the boulders up the hill at the same timeâ€ in response to a question about balancing effort on science vs policy. Allusions to Sisyphus!
Yet he provided some hope too, highlighting a recent CDC studyÂ that models how a coordinated response to antibiotic resistance in health care facilities could substantially cut infections. Read more