Want to Beat Antibiotic-Resistant Superbugs? Rethink That Strep Throat Remedy

Got a sore throat? The doctor may write a quick prescription for penicillin or amoxicillin, and with the stroke of a pen help diminish public health and your own future health by helping bacteria evolve resistance to antibiotics.

It’s time to develop alternatives to antibiotics for small infections, according to a new thought paper by scientists at the Georgia Institute of Technology, and to do so quickly. It has been widely reported that bacteria will evolve to render antibiotics mostly ineffective by mid-century, and current strategies to make up for the projected shortfalls haven’t worked.

One possible problem is that drug development strategies have focused on replacing antibiotics in extreme infections, such as sepsis, where every minute without an effective drug increases the risk of death. But the evolutionary process that brings forth antibiotic resistance doesn’t happen nearly as often in those big infections as it does in the multitude of small ones like sinusitis, tonsillitis, bronchitis, and bladder infections, the Georgia Tech researchers said.

“Antibiotic prescriptions against those smaller ailments account for about 90 percent of antibiotic use, and so are likely to be the major driver of resistance evolution,” said Sam Brown, an associate professor in Georgia Tech’s School of Biological Sciences. Bacteria that survive these many small battles against antibiotics grow in strength and numbers to become formidable armies in big infections, like those that strike after surgery.

“It might make more sense to give antibiotics less often and preserve their effectiveness for when they’re really needed. And develop alternate treatments for the small infections,” Brown said.

Brown, who specializes in the evolution of microbes and in bacterial virulence, and first author Kristofer Wollein Waldetoft, a medical doctor and postdoctoral research assistant in Brown’s lab, published an essay detailing their suggestion for refocusing the development of bacteria-fighting drugs on December 28, 2017, in the journal PLOS Biology.

Duplicitous antibiotics

The evolution of antibiotic resistance can be downright two-faced.

“If you or your kid go to the doctor with an upper respiratory infection, you often get amoxicillin, which is a relatively broad-spectrum antibiotic,” Brown said. “So, it kills not only strep but also a lot of other bacteria, including in places like the digestive tract, and that has quite broad impacts.”

E. coli is widespread in the human gut, and some strains secrete enzymes that thwart antibiotics, while other strains don’t. A broad-spectrum antibiotic can kill off more of the vulnerable, less dangerous bacteria, leaving the more dangerous and robust bacteria to propagate.

“You take an antibiotic to go after that thing in your throat, and you end up with gut bacteria that are super-resistant,” Brown said. “Then later, if you have to have surgery, you have a problem. Or you give that resistant E. coli to an elderly relative.”

Much too often, superbugs have made their way into hospitals in someone’s intestines, where they had evolved high resistance through years of occasional treatment with antibiotics for small infections. Then those bacteria have infected patients with weak immune systems.

Furious infections have ensued, essentially invulnerable to antibiotics, followed by sepsis and death.

Alternatives get an “F”

Drug developers facing dwindling antibiotic effectiveness against evolved bacteria have looked for multiple alternate treatments. The focus has often been to find some new class of drug that works as well as or better than antibiotics, but so far, nothing has, Brown said.

Wollein Waldetoft came across a research paper in the medical journal Lancet Infectious Diseases that examined study after study on such alternate treatments against big, deadly infections.

“It was a kind of scorecard, and it was almost uniformly negative,” Brown said. “These alternate therapies, such as phage or anti-virulence drugs or, bacteriocins — you name it — just didn’t rise to the same bar of efficacy that existing antibiotics did.”

“It was a type of doom and gloom paper that said once the antibiotics are gone, we’re in trouble,” Brown said. “Drug companies still are investing in alternate drug research, because it has gotten very, very hard to develop new effective antibiotics. We don’t have a lot of other options.”

But the focus on new treatments for extreme infections has bothered the researchers because the main arena where the vast portion of resistance evolution occurs is in small infections. “We felt like there was a disconnect going on here,” Brown said.

Don’t kill strep, beat it

The researchers proposed a different approach: “Take the easier tasks, like sore throats, off of antibiotics and reserve antibiotics for these really serious conditions.”

Developing non-antibiotic therapies for strep throat, bladder infections, and bronchitis could prove easier, thus encouraging pharmaceutical investment and research.

For example, one particular kind of strep bacteria, group A streptococci, is responsible for the vast majority of bacterial upper respiratory infections. People often carry it without it breaking out.

Strep bacteria secrete compounds that promote inflammation and bacterial spread. If an anti-virulence drug could fight the secretions, the drug could knock back the strep into being present but not sickening.

Brown cautioned that strep infection can lead to rheumatic heart disease, a deadly condition that is very rare in the industrialized world, but it still takes a toll in other parts of the world. “A less powerful drug can be good enough if you don’t have serious strep throat issues in your medical history,” he said.

Sometimes, all it takes is some push-back against virulent bacteria until the body’s immune system can take care of it. Developing a spray-on treatment with bacteriophages, viruses that attack bacteria, might possibly do the trick.

If doctors had enough alternatives to antibiotics for the multitude of small infections they treat, they could help preserve antibiotic effectiveness longer for the far less common but much more deadly infections, for which they’re most needed.

Nova Southeastern University Researchers Studying How to Disrupt Bacteria to Treat Infections

Bacteria are everywhere. And despite widespread belief, not all bacteria are “bad.” However, to combat those that can cause health issues for humans, there has been an over-reliance on the use of antibiotics – so much so, that many of them are now proving ineffective due to bacteria developing increased resistance to them.

“More and more antibiotics are essentially becoming useless,” says Robert Smith, Ph.D., assistant professor in the Department of Biological Sciences at NSU’s Halmos College of Natural Sciences and Oceanography. “Even the most routine infections, such as ear infections that are often seen in children, are becoming more challenging and expensive to treat.”

This notion isn’t new – just prior to winning his Nobel Prize in 1945, Alexander Fleming, the scientist who discovered antibiotics, warned that overusing them would lead to bacteria that were no longer killed by these drugs.  Since then, scientists and bacteria have been locked in a deadly arms race. While scientists rush to discover new antibiotics, bacteria fight back by developing new tools to resist antibiotics. In recent years, the bacteria have been winning.

So this paradigm led researchers at NSU to take another look at how bacteria do what they do to see if there was another way to approach this issue. Researchers are now focusing on developing new ways to treat infections that reduce the use of antibiotics. And what the NSU researchers found, working with colleagues from Duke University and the University of Minnesota, was interesting.

Their findings are detailed in the March 27th edition of Scientific Reports (http://www.nature.com/articles/s41598-017-00588-9).

One way that bacteria infect people is by working together. First, they build a home called a biofilm, and then use chemicals to “talk with each other.” This allows the bacteria to coordinate an attack on the infected person. Led by NSU graduate Cortney Wilson, Smith’s lab recently discovered that by shaking the house that the bacteria have built, the ability of the bacteria to talk to one another is affected. Wilson earned her Master’s from NSU and is now at the University of Colorado, Boulder.

“We found that shaking the bacteria forced them to face a decision; do they want to grow, or do they want to cooperate,” Smith said. “And if we shook them at just the right frequency, we created enough confusion that the bacteria could do neither effectively.”

Smith notes that this strategy to prevent bacteria from talking to one another has promise in reducing the need for antibiotics. The team of scientists hope to begin testing their theory in more species of bacteria, and eventually in mice.

“It is a very exciting time for our research team. We are looking forward to building upon our very promising results and to moving our strategy into the clinic.”

Queen’s Research Discovers Vitamins Could Help Treat Cystic Fibrosis

Researchers from Queen’s University Belfast have discovered why antibiotics for treating people with cystic fibrosis are becoming less effective and how fat soluble vitamins might offer a viable solution.

A team of researchers led by Professor Miguel Valvano, from the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University Belfast, has discovered why some particularly harmful bacteria are not responding to antibiotics.

The bacteria, Burkholderia cenocepacia, are highly antibiotic resistant and cause severe lung infections in people with cystic fibrosis.

This research study, recently published in the international journal mBio, unveiled that the administration of fat-soluble vitamins could increase the effectiveness of the antibiotics used to treat cystic fibrosis infections.

Lipocalins, the antibiotic-capturing proteins, latch on with more strength to fat-soluble vitamins than to the antibiotics. Therefore, fat-soluble vitamins such as vitamin E could help to improve antibiotic treatment by freeing the antibiotics from the lipocalins and allowing them to reach the target bacteria to fight the infection.
Speaking about this breakthrough, Professor Valvano explains: “Antibiotic resistance is a global phenomenon which prevents the effective treatment of diseases. Our research shows that bacteria not only can resist the action of antibiotics once they are internalised but can also capture antibiotics before they reach and penetrate into the bacterial cells.

“This is an exciting and potentially life-changing finding, particularly relevant for cystic fibrosis patients who are chronically infected with multi-resistant bacteria. Armed with this knowledge, we can focus our efforts on finding alternative solutions to more effectively treat the infection in these patients.

“Fat-soluble vitamins can ‘soak up’ the lipocalins before they have a chance to bind the antibiotics, increasing the chances that antibiotics will reach the bacteria.
“We are now exploring ways to reformulate antibiotics together with relevant vitamins for delivery into cystic fibrosis patients and assess their efficacy, so that patients can benefit from these findings.”

Lung infections, mostly caused by bacteria, are a serious and chronic problem for people living with cystic fibrosis and are often treated with inhaled antibiotics. Over time, bacteria in the lungs can become resistant to antibiotics making it increasingly difficult to treat lung infections and leading to irreversible damage to the lungs.