Sep
26
2020

A New Antibiotic Against Methicillin Resistant Staphylococcus aureus

A US study describes a new antibiotic against methicillin resistant Staphylococcus aureus. It is a lysin-based antibacterial agent.

Physicians have been looking for years for a solution regarding the increasing antibiotic resistance problem. But several attempts in the past have failed.

Staphylococcus infections are the most common bacterial infections of human skin, of soft tissue, joints, bones, and pneumonia. In addition, it can cause endocarditis (=infection of heart valves) and lead to blood poisoning (septicemia).

Staphylococcus aureus is the underlying bacterium behind staph infections. With the introduction of new antibiotics  it takes only 1 to 2 years before this bacterium learns to become resistant. Researchers noticed that the bacteria start to produce lysins and suddenly they are resistant to the latest antibiotic. Further research zeroed in on lysostaphin, which was active against resistant Staphylococcus bacterial strains.

Deimmunized lysostaphin

Lysostaphin is an antibacterial peptide described here in detail. But there still was some interference with immunologically active surface antigens that scientists were later able to overcome. Researchers succeeded lately in removing some of the surface antigens and develop deimmunized lysostaphin. This is what this publication is all about.

It describes how T cells cannot detect the surface antigen properties of deimmunized lysostaphin. This way none of the strength of deimmunized lysostaphin gets lost in the fight against resistant staphylococcus that normally form anti-drug antibodies. Researchers pointed out the importance of the deimmunization process to make deimmunized lysostaphin invisible to the T cells of the immune system.

Vigorous testing of deimmunized lysostaphin

The researchers who investigated the efficiency and safety of deimmunized lysostaphin did the following tests.

  • Although lysostaphin was deimmunized, it retained potent in vitro and in vivo anti-staphylococcal activity. In vitro studies involving Petri dishes with methicillin resistant Staphylococcus aureus showed the effectiveness of deimmunized lysostaphin. In vivo testing in a mouse and rabbit model also showed effectiveness.
  • Deimmunized lysostaphin showed reduced immunogenicity in vivo. Researchers tested this in mice and compared the results to regular lysostaphin, where there was a swift immunological response.

More points regarding deimmunized lysostaphin

  • Immune evasion allows for repeated efficient dosing of deimmunized lysostaphin. This means that the physician can administer the antibiotic (the deimmunized lysostaphin) to fight the methicillin resistant Staphylococcus aureus with several daily doses.
  • The deimmunization process allows deimmunized lysostaphin to evade the immune response that occurs to regular lysostaphin. This prevents future resistance development. It also prevents that the immune responses weaken the anti-methicillin resistant Staphylococcus aureus response.
  • Researchers showed in a difficult rabbit endocarditis model that deimmunized lysostaphin treats MRSA infection successfully. Endocarditis is an infectious disease, which is both difficult to treat in rabbits, but also in humans. For this reason, rabbits are often used as a model when new antibiotics are developed. If they are successful in the rabbit model they often get approval later for human treatments.

Deimmunized lysostaphin in humans

Unfortunately, we are still a few years away from using deimmunized lysostaphin in humans. After successful use of lysostaphin in mice and rabbits the next logical application is to launch human clinical trials. I am convinced that this will be the next step and very likely will be successful.

A New Antibiotic Against Methicillin Resistant Staphylococcus aureus

A New Antibiotic Against Methicillin Resistant Staphylococcus aureus

Conclusion

Researchers found a new antibiotic against methicillin resistant Staphylococcus aureus in a lysin-based antibacterial agent. This peptide has surface antigens that scientists had to removed to make it more effective. The end result was a deimmunized lysostaphin. Researchers tested this new antibiotic that is effective against many antibiotic resistant strains of bacteria successfully in mice and rabbits. The next step is testing in humans. This involves several phases of clinical trials. These clinical trials have to show that there is a lack of toxicity. In addition, they have to show that the new antibiotic is effective against resistant bacteria. I estimate that this process can still take about 5 years from now before the clinician can use this antibiotic routinely. As the new antibiotic is a polypeptide, it the patient cannot take it orally, as the gut is digesting it. The patient has to take it by injection.

Jun
27
2020

A New Antibiotic, Teixobactin Can Overcome Antibiotic-Resistant Superbugs

A new antibiotic, teixobactin can overcome antibiotic-resistant superbugs. The discovery of teixobactin took place in 2015. It is a peptide with 11 amino acid units. Teixobactin is derived from a gram-negative bacterium, Eleftheria terrae. It is the first of a new class of antibiotics that can kill superbugs. Two examples, for instance are methicillin-resistant Staphylococcus aureus and resistant Mycobacterium tuberculosis. Researchers have been battling with difficult solubility of teixobactin and problems synthesizing this peptide in the laboratory. Teixobactin binds to the membranes of the bacteria it fights. This is a new mechanism for this new class of antibiotics, different from conventional antibiotics.

Mechanisms of fighting bacteria resistant to conventional antibiotics

But it is exactly this quality that is necessary to fight the antibiotic-resistant bacteria. The researchers showed that teixobactin binds weakly to a component of the bacterial cell wall, called “Lipid II”. But they found a second mechanism, namely blocking precursors of cell membrane synthesis in the bacteria they fight. Because of these unique mechanisms it is possible for them to fight a multitude of bacteria resistant to conventional antibiotics. Teixobactin has a unique molecular structure, which makes it difficult for resistant bacteria to develop resistance to it.

Antibiotic resistance

Resistance to antibiotics is a worldwide problem. There are several factors that worked together to make antibiotic resistance such a big issue. For instance, in the past many doctors prescribed antibiotics for any viral cold, even knowing that antibiotics only work against bacteria. Aside from this, the agricultural practice of using antibiotics as a growth stimulator is also an important factor for antibiotic resistance to develop. It is the bacteria that become resistant, not the human body. Several clinical entities involving resistant bacteria exist that show the magnitude of the problem.

Flesh-eating disease

Necrotizing fasciitis (or flesh-eating disease) can develop when you swim in contaminated waters and the bacterium, Vibrio vulnificus enters through skin sores or wounds. The CDC warns that you should stay out of salt water or brackish water, if you have a skin wound. The flesh-eating bacteria, Vibrio vulnificus can become very aggressive, once it has entered the body. Right now, 1 out of 5 people who get infected will die and many people require ICU treatment. Others need limb amputations. All of this can happen within only 1 or 2 days of becoming ill. The hope is that with the development of teixobactin as an injectable medication or as an oral pill there will no longer be deaths, amputations and scarring due to this bacterium, as the antibiotic will very quickly eradicate Vibrio vulnificus. I have previously written about what hospitals can do to fight superbugs.

The most common antibiotic-resistant bacteria

Here is a brief review of the most common antibiotic-resistant bacteria.

Mycobacterium tuberculosis

Since the 1950’s and 1960’s tuberculosis was treatable with a combination of two antibiotics over a period of six months to two years. But in the last 10 years more and more resistant strains of tuberculosis have developed. This is called multi-drug-resistant TB. In 2013 statistics showed that 3.7% of newly diagnosed tuberculosis cases were multi-drug-resistant TB. Many of these cases can be traced back to prisons and homeless shelters.

Methicillin-resistant Staphylococcus aureus (MRSA)

MRSA has become a common resistant bacterium that can present with difficult to treat boils in the skin, but also as a fulminant infection as necrotizing fasciitis (or “flesh-eating disease”). About 1/3 of the cases of flesh-eating disease are caused by MRSA.

Clostridium difficile (C. difficile)

This gut bacterium is naturally resistant to many antibiotics. The rest of the gut bacteria usually suppress the growth of C. difficile. But many patients can get overgrowth of C. difficile in their gut following treatment with antibiotics. Recolonization with probiotics can help to reintroduce a balanced bowel flora. In the US about 500,000 individuals come down every year with diarrhea due to C. difficile. This leads to approximately 15,000 deaths yearly.

Vancomycin-resistant Enterococci (VRE)

Physicians find enterococci in the gut and the female genital tract of patients. They can become resistant when the patient is treated with vancomycin for another infection. The VRE can then become a problem of its own with difficult to treat infections in the genital tract of females, the gut or in wounds from surgery. It has become a problem in immunocompromised patients.

The gonorrhea causing bacteria

In the last 70 to 80 years Neisseria gonorrhoea, the cause of gonorrhea, has been treated with only one antibiotic, but gradually the bacterium developed antibiotic-resistance. Lately, with more and more resistant strains of Neisseria gonorrhoea, the CDC has recommended to treat gonorrhea with two overlapping antibiotics.

Carbapenem-resistant Enterobacteriaceae (CRE)

There are two problem bugs among this category of enterobacteria, Klebsiella species and Escherichia coli (E. coli). These bacteria reside in hospitals where they can accumulate and are present in patients with immune system compromise. Medical devices like catheters and ventilators transmit these bacteria. Once a patient is sick with CRE, there is a danger of blood poisoning (septicemia), which has a high death rate.

How do regular antibiotics kill bacteria and how can they become resistant?

Normally, when antibiotics are not resistant, they interfere with the cell membrane production of the bacteria. Specifically, conventional antibiotics prevent bacteria from synthesizing a molecule, called peptidoglycan. Without peptidoglycan bacteria are not stable enough to survive in humans. But there are other mechanisms as explained in this link how antibiotics manage to kill bacteria.

Now I like to address the question how bacteria can become resistant to conventional antibiotics. This happens with overuse of antibiotics, i.e. prescribing antibiotics when a person suffers from a viral illness where antibiotics do not work. Other overuse comes from agriculture where cattle in feed lots get antibiotics as growth promoters. The FDA is strongly criticizing this practice, because residuals of antibiotics in beef can alter the bowel flora in man. The antibiotics kill all the sensitive bacteria. But the resistant bacteria, that have undergone mutations and adapted to the antibiotics, will survive.

Why teixobactin and analogues can avoid resistance

Since the detection of teixobactin many analogues have been synthesized. A new antibiotic, teixobactin can overcome antibiotic-resistant superbugs. The teixobactin analogues need more fine tuning, but they will be a breakthrough in the treatment of resistant bacteria. As this peptide attacks two targets on bacteria, it is not easy for bacteria to develop resistance against these new antibiotics.

A New Antibiotic, Teixobactin Can Overcome Antibiotic-Resistant Superbugs

A New Antibiotic, Teixobactin Can Overcome Antibiotic-Resistant Superbugs

Conclusion

Resistant bacteria have become a serious health concern in the last decade. Physicians overprescribing antibiotics and farmers feeding antibiotics to cattle in feedlots as growth promoters were the driving forces. In 2015 came the breakthrough and discovery of teixobactin. This is a peptide with 11 amino acid units. Teixobactin is a derivative of a gram-negative bacterium, Eleftheria terrae. A new antibiotic, teixobactin can overcome antibiotic-resistant superbugs. In the meantime, researchers have been able to improve solubility by developing teixobactin analogues. More research is necessary. But all of the researchers who work in this field claim that this will very soon be extremely useful for patients with super bugs. This super-antibiotic will be a weapon fighting super bugs. Before the release of this medication clinical trials will be the next step.

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May
25
2013

What We Can Do About Superbugs

Introduction

This article is about what we can do about superbugs. Several decades ago nobody talked about superbugs. Then came stories of “flesh-eating disease” or necrotizing fasciitis. Since 2001 it became obvious that these cases have become more common. Methicillin-resistant Staphylococcus aureus (MRSA) was often the underlying cause.

Antibiotics for weight gain in cattle

Government bodies accuse physicians of overprescribing unnecessary antibiotics for viral colds and flus. All physicians had to attend educational programs as part of the continuing education programs to use antibiotics only sparingly.  But the frequency of these serious infections often requiring amputations and mutilating surgeries continued to escalate. Research into the phenomenon of increasing superbugs took place already in the 1970’s. In 1977 the FDA came to the conclusion that antibiotics were used widely in the US by the agroindustry for weight gain in livestock (pigs, cattle, chicken, turkeys). Although masked as protecting animals from infections, the real motivation of the farmer was to increase profits. The FDA recommendation in 1977 to change the practice of feeding livestock antibiotics did nothing to change that.

Farmers continued to use the old antibiotic feeding practice

After a court review in 2012 a New York court ordered the FDA to do something about the same problem. The answer was a lame recommendation of a voluntary program to downsize the use of antibiotics in livestock, requiring a vet and a prescription for antibiotics. The problem with this is that farms had no mandatory checks of livestock by trained inspectors. The ruling about antibiotic reduction contained no penalties for farmers who continued the old antibiotic feeding practice. Fast-forward to an American citizen who visited India recently as told in this story.

Superbugs are all over the world

It is clear that superbugs are all over the world. It is also clear from this article (and other literature I have reviewed) that 80% of today’s antibiotics are fed to livestock, not to treat infections, but because of their effect on weight gain in livestock and the associated larger profits. The result is that we are looking at farming practices that produce deadly superbugs. Next we are reading headlines about a recall of meat meat and meat products.

Here is an interesting list from the Environmental Working Group, which shows what percentage of meats in your neighborhood grocery store is contaminated, and these are the numbers for superbug contaminations: The worst is ground turkey with 81%, pork chops with 69%, ground beef with 55% and chicken breasts, wings or thighs with 39%.

What We Can Do About Superbugs

What We Can Do About Superbugs

Wash meat thoroughly

This shows how important it is to wash meat thoroughly and to cook it long enough to kill the superbugs. It is also extremely important to frequently wash your hands when you prepare meat. This avoids  colonizing your skin surface with superbugs. The first step is for a person to have skin surface flora with superbugs. The second step is to get a small abrasion or a skin sore where a superbug can enter. The final step is that this bug multiplies under the surface of the skin and starts a serious infection. If the immune system is not in top shape to eradicate these bugs right away, the next step may be flesh-eating disease or toxic shock syndrome.

Solutions to stay on top of Superbugs

In northern Saskatchewan, one the provinces of Canada, an 8 year community based study was done to see whether it would be possible to reduce community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) by a combination of hand washing and education regarding appropriate antibiotic use. Using this program it was shown that in the time period of 2006 to 2008 the infection rates went down from 242.8 to 129.3 infections/10,000 population, which is almost half of the infection rate from before.

Hospital associated methicillin-resistant Staphylococcus aureus

What can physicians and nurses do about hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and other superbugs in the hospital? In a hospital it is extremely important that HA-MRSA free patients do not get exposure to this superbug . Their immune system is already weak from the underlying disease. This is how they got into the hospital. At Stanford University a robot was developed that emits pulsating ultra violet light to kill any leftover superbug after the initial cleanup with scrubbing using bleach and germicidal solutions. Support staff treat the isolation rooms with the double treatment and robots disinfect the operating rooms overnight. So far tests have shown a complete eradication of the superbugs with these methods.

Breaking the chain of infection

Since about 2005 the major food production animals have been shown to be colonized with superbugs (MRSA) as this publication shows.

With 80% of the world’s production of antibiotics still going into the agroindustry for weight gaining purposes, it is high time that international “laws with teeth” apply. The WHO needs to get action in this and the public needs to put pressure on politicians to achieve this. Medical history has shown that infectious epidemics can be cured by breaking the chain of infection. In the example regarding superbugs the story of interrupting the chain of infection is exactly the same here: As shown in this study from Stanford University MRSA bugs are not contained in organic foods. So, by attempting to eat 100% organic, which can be challenging at times, you can intercept the infectious cycle involving MRSA and other Superbugs.

Attempt to eat mostly organic foods

You do not get exposed to the meat from food production animals treated with antibiotics for growth purposes. In the meantime, you are protecting yourself by keeping fit, taking vitamins and supplements all with the hope that the immune system stays strong from this. By eating organic meats and meat products you also keep your body free of toxins that would weaken your immune system and set you up for getting autoimmune diseases down the road.

The end result is that people who follow this example avoid colonization from exposure to superbug-infected meat products.  At the same time this prevents exposure to other toxins that a manufacturer of organic food can not use. Here is a story of a company that produces meat products without antibiotics (organic meats).

Conclusion

You can interrupt the infectious cycle of superbugs by eating organic foods. Make sure your immune system is strong by exercising, supplementing with vitamins and minerals. Wash your hands with soap and clean water, particularly after handling meat or meat products. Do not take antibiotics for a long time unless there is a specific reason of  bacterial infection that requires it. Do not consume meats from animals that were fed antibiotics. Read food labels!

References

1. Stick to organically grown meats:  http://www.helpguide.org/life/organic_foods_pesticides_gmo.htm

2. Super bugs in hospitals:  http://patients.about.com/od/atthehospital/a/hais.htm

3. Useful 2008 article : hand washing, reducing antibiotic use in humans and in animal feed are the solution to combat superbugs. http://evolution.berkeley.edu/evolibrary/news/080401_mrsa

Last edited May 25, 2013

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Aug
01
2007

New Cure For Drug Resistant Bacteria At The Horizon

Drug resistant bacteria (like MRSA, methicillin resistant Staphylococcus aureus) have developed in many hospitals and have caused more than 2 million infections in the US alone of which 90,000 people died. Yet so far research regarding this problem has been very slow and unsuccessful. In Canada there was an outbreak of E.coli, which left 14 people severely ill and simultaneously there was a similar outbreak in the US leaving three people dead.

Dr. Redinbo, PhD in biochemistry and biophysics, from the University of North Carolinaat Chapel Hill made an astounding discovery in his lab. He tested some of the older medications used for osteoporosis treatment, the biphosphonates clodronate and etidronate, to see whether they would have an effect on stopping the multiplication of these harmful bacteria. Dr. Redinbo’s work was published in the July 13 edition of the Proceedings of the National Academy of Sciences. Dr. Redinbo’s team found that an enzyme, called relaxase, is at the center of the development of antibiotic resistance. When resistance develops, there is a genetic transformation that takes place, like a mini Darwinian selection process where the most resistant bacteria survive and multiply. The resistant bacteria mate with each other and with bacteria that are not yet resistant. This process involves the relaxase enzyme system, some DNA stranding and a strand exchange. In this way new resistant bacteria are formed. Experiments under the supervision of Dr. Redinbo found that this process can be stopped by the phosphate-rich compound, biphosphonates (clodronate and etidronate). Other chemicals were found to not be as effective.

New Cure For Drug Resistant Bacteria At The Horizon

New Cure For Drug Resistant Bacteria At The Horizon

The relaxase system is found in a number of problem bacterial strains, Staphylococcus strains, drug resistant Acinetobacter strains and others. Unfortunately the biphosphonates have some side-effects like stomach soreness and birth defects. The researcher said that he hopes that these drugs and perhaps others with less side-effect will offer new treatments for antibiotic resistant bacteria.

Reference: July 13, 2007 edition of the Proceedings of the National Academy of Sciences

Last edited December 5, 2012