Breakthrough: Scientists fight nasty large intestine disease with new Merck drug Bezlotoxumab to battle Clostridium Difficile

Breakthrough: Scientists fight nasty large intestine disease with new Merck drug Bezlotoxumab to battle Clostridium Difficile

It's called C. diff, and it kills nearly 30,000 people every year -- now, scientists may have an answer.

A groundbreaking new drug produced by Merck & Co. may help scientists battle against a terrible disease of the large intestine that is killing nearly 30,000 people per year.

The Centers for Disease Control and Prevention (CDC) estimates that Clostridium difficile, also known as “C. diff,” is responsible for 453,000 cases every year and 29,300 related deaths based on a 2011 study. It’s a disease that ravages the large intestine and primarily affects people who are 65 years of age and older, and the disease works fast, typically killing one out of every nine patients in just 30 days after diagnosis.

But now, there is hope. An experimental antibody that has been developed by Merck & Co. was shown in studies to reduce by about 10 percentage points the risk of coming down with the C. diff bacterium, according to a Reuters report.

Typically, C. diff is treated with antibiotics, but that also kills off friendly bacteria that can keep the disease under control.

However, the new Merck drug showed that in two Phase 3 studies that were presented at a medical meeting in San Diego the risk of C. difficile recurring was down to about 15 percent after 12 weeks of treatment with antibiotics and one infusion of bezlotoxumba, the drug that scientists hope could be key in blocking the disease by preventing it from binding to cell. That compares to about a 25 percent rate of recurrence for just antibiotics and a placebo.

This is important because things get a lot harder after the first recurrence, when the rate of recurrence again rises to 40 or even 60 percent after a second infection.

Unfortunately, another experimental antibody known as actoxumab showed no benefit in the experiements, either alone or along with bezlotoxumab. As a result, scientists discontinued using actoxumab.

But the strong showing of bezlotoxumab has resulted in Merck pushing to file for regulatory approval of the antibody. It has been licensed at Bristol-Mysers Squibb-owned Massachusetts Biologic Laboratories and Medarex.

There are side effects to taking the drug, including nausea, diarrhea, and urinary tract infection.

C. diff has been on the rise over the last two decades and is the largest cause of infections acquired at healthcare facilities in the United States, according to the CDC as quoted in the report.

Companies are hard at work trying to produce a vaccine against C. difficile. There are treatments available, including what are known as “stool transplants” when fecal matter from a healthy person is inserted into the gut of someone in order to reintroduce friendly bacteria that has been wiped out.

C. difficile infections typically happen when someone gets exposed to a pathogen when they are receiving an antibiotic treatment for another illness, which explains why its occurrence is so common at healthcare centers. Because the antibiotics suppress normal bacteria in the colon, C. diff can flourish and produce toxins that result in severe diarrhea, severely dehydrating patients and causing damage to the colon that can cause bacteria to leak dangerously into the bloodstream.

A total of two-thirds of all cases were found by the CDC to have been caused at a hospital or nursing home. Most deaths are elderly patients.

What can be done about it? The best way is probably to make sure you are eating a diverse diet, but perhaps better than that is simply to avoid antibiotics that aren’t entirely necessary, as they can leave your gut dangerously low on good bacteria. As always, the best way to discuss the risks is to talk to your doctor.

C. diff, also called Clostridium difficile colitis or pseudomembranous colitis, is colitis, or inflammation of the large intesting. It is the result of an infection of the C. diff bacterium, which is a spore performing bacterium. It results in infectious diarrhea, with symptoms resembling that of the flu and may be confused with inflammatory bowel disease. The toxins released by C. difficile include bloating, diarrhea, and abdominal pain that can become very severe and even debilitating.

Basically, scientists think it happens when the bacteria replaces normal gut flora that has been compromised from an antibiotic treatment regimen for some other infection, paving the way for C. diff to take over the gut and wreak havoc. As a result, it becomes a condition that is difficult to reverse, and often involves doctors resorting to taking healthy fecal matter from someone else and inserting it into the person with the infection, as the C. difficle bacteria has taken over the intestinal microbiome.

Not all cases are severe. Some mild cases of C. difficile can simply be wiped out by discontinuing use of antibiotics, but once it gets back, doctors are forced to use a targeted antibiotic treatment. As have been found in studies, about a quarter of people who are treated relapse, and the disease becomes even more ingrained in the microbiome and more difficult to remove.

Signs and symptoms range from some diarrhea that is not serious to a life-threaning colon inflammation. Doctors tend to use a clinical prediction rule to spot C. diff cases early, taking note of significant diarrhea, which would be more than three partially formed or water stools over 24 hours, and recent exposure to antibiotics, along with other symptoms like fever or abdominal pain.

Children with CDI tend to have a watery diarrhea and at least three bowel movements per day for at least two days, along with the other typical symptoms for C. diff.

The C. difficile bacteria is a very interesting species. It is an anaerobic motile bacteria which is found mostly in soil. They look like long, irregular, almost drumstick-shaped cells when looked at under a microscope. They have a bulge at one of their ends. They like to grow on the blood agar at human body temperatures. They produce spores when they are stressed that can handle more extreme conditions than typical bacteria, which explains their toughness and difficulty to remove. Scientists think that it is present in 2 to 5 percent of the adult population.

C. difficile typically produes a number of toxins, one an enterotoxin and the other a cytotoxin. They both are capable of producing symptoms of inflammation and diarrhea, although scientists don’t yet have a handle on example which does which.

C. diff is mostly transferred via fecal to oral route. The reason why they are so easy to spread is that the spores are incredibly tough, and are not killed by the usual alcohol-based hand cleansers that are used in medical facilities. The spores can survive in a clincial environment for quite a while, and therefore it can come from just about any surface. Once the spores get inside the body, they have an acid resistance that allows them to move through the tomach and get to the colon, where they thrive.

The average human digestive tract has a whopping 1,000 species of microorganisms. While this sounds unpleasant, most of them are harmless, and some are even beneficial. This is why it is so important that nothing upsets the balance of these organisms, and when it does, C. diff infections can be the result.

Patients who are in hospitals or long-term health care facilities are at the highest risk, especially those who rely on long-term treatment with antibiotics.



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