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Op-Ed: The myths around Teixobactin

First off, what has happened? On Wednesday the respected science journal Nature published a research paper about a new class of antibiotic. This in itself is significant since a new class of antibiotic has not been discovered since 1987. The research paper is titled “A new antibiotic kills pathogens without detectable resistance.”

Secondly, as I have written on Digital Journal, blogs and in the academic press (for example the Journal of Microbiology and Pathology), the antibiotic crisis is the greatest threat, within the field of science and medicine, faced by humanity. Since the 1940s we have enjoyed a spectrum of natural and synthetic compounds that have enabled us to go into hospital, have an operation with the risks of cross-contamination from bacteria located in the outside environment (or from the improperly sanitized hands of surgeons) minimized because if such infections occur a short course of antibiotics will rapidly clear up the infection. Importantly antibiotics help to reduce the risk of potentially life threatening complications in surgery, chemotherapy and transplantation.

The antibiotic crisis has arisen because pathogenic microbes continue to grow after exposure to one or more antimicrobial agents due to genetic modifications that impart resistance. This happens when a low number of microbial cells survive after a course of antibiotics and through one of several mechanisms evolve to form a variant strain that is resistant to a given antibiotic. This means that an alternative antibiotic needs to be administered. The risk is then that a bacterium becomes resistant to multiple antibiotics and this process continues until there are no effective antibiotics left (here the phrase “multi-drug resistant” (MDR) is used). Or, it means that relatively mild antibiotics, with few side effects, can no longer be administered and more potent antibiotics, which carry inherent risks, need to be used. An example here are carbapenems, where this class of chemicals are often used as the antibiotics of last resort.

Side effects of antibiotics that affect the digestive system include:

Being sick,
Feeling sick,
Bloating and indigestion,
Abdominal pain,
Loss of appetite.

Common types of drug-resistant bacteria, and those commonly termed as “superbugs”, include: MRSA (methicillin-resistant Staphylococcus aureus), VRSA (vancomycin-resistant S. aureus), ESBL (extended spectrum beta-lactamase), VRE (vancomycin-resistant Enterococcus) and MRAB (multidrug-resistant Acinetobacter baumannii). Each of these pathogens is also associated with hospital acquired infections.

This process of antibiotic resistance has been accelerated through over-use (although, arguably, acquired resistance would have happened any way). Over-use has occurred through medics handing antibiotics for no good reason (a common case here is for people who have viral infections like the common cold or influenza) other than to placate the patient through the handing over of what is, in effect, a placebo.

The age of the superbug, although genetically inevitable, need not have affected society to the extent that it has. The reason why no new antibiotics have emerged for near-on thirty years is not because it has been beyond human ingenuity to create synthetic ones or we have exhausted the thrall through the microbial species of the world (many antibiotics are derived from other microbes, the classic example being penicillin which is a group of antibiotics derived from Penicillium fungi.) The reason is that pharmaceutical companies went through a period of not researching and developing them because of the very low return on investment. This changed a little a few years ago when governments were forced, as a result of the crisis, to incentivize “big pharma” (see, for instance, U.S. Senator Sherrod Brown’s Strategies to Address Antimicrobial Resistance (STAAR) Act.) Nonetheless, most of the new research, including Teixobactin, has arisen from the university sector (although there has always been a relationship between universities and industry since the private sector is a key source of funding.)

Another reason for the problem has been with some farmers, mainly those who engage in intensive farming methods, adding antibiotics to animal feed in order to boost the meat quantity. This has not only accelerated resistance it has allowed antibiotic resistant bacteria to reach communities through farming practices like waste run of into streams.

With this context established, what about Teixobactin? It is a new class of antibiotic (class refers to the mechanism by which it inactivates or destroys a bacterial cell). It does not, however, represent the only antibiotic to be discovered and given approval within the last twelve months. Two other compounds have recently been approved by the U.S. Food and Drug Administration (FDA). These are Dalvance, which is an intravenous drug that can treat skin and soft tissue infections, and the launch was reported on by Digital Journal. Dalvance is intended to treat acute bacterial skin and skin structure infections.

The second antibiotic was Sivextro or, for its non-commercial name, tedizolid phosphate. The antibiotic, again reviewed on this digital platform, has been approved for intravenous or oral use to treat severe MRSA. Other work has been taking place using gene editing, among other research projects, to stop bacteria in their tracks. For those interested in other research I wrote a review paper for the journal Microbiology & Infectious Diseases last year which summarizes what has been happening.

Now, let us consider Teixobactin itself. What has the research shown?

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A team from Northeastern University in Boston working with a small biotech company called NovoBiotic Pharmaceuticals have discovered a novel antibiotic, called ‘Teixobactin’. Teixobactin has impressive activity against a range of Gram-positive pathogens of importance to healthcare including S. aureus, various streptococci, and, importantly, Clostridium difficile (“C diff”.) The scientists found that Teixobactin had equivalent activity to oxacillin (methicillin) in vitro, and superior activity to vancomycin both in vitro and in an animal model.

Without wishing to go into the science of microbiology in too much detail, you’ll not the phrase “Gram-positive” used. Bacteria, for around 130 years, have been differentiated into two morphological groups based on a microscopic staining reaction which is based on the components of their cell wall. This divides bacteria into Gram-positive and Gram-negative. These groups of bacteria generally prefer different environments (such as Gram-positive bacteria occurring on skin and Gram-negatives in water.) All of the bacteria listed in relation to the destructive properties of Teixobactin are Gram-positive. There is no mention of Gram-negatives like Pseuomonads or Klebsiella.

This is because Teixobactin does not work against these types of bacteria. The reason is simple: Teixobactin is a extracted from a type of Gram-negative called Elftheria terrae. This means that the types of bacteria that Teixobactin can kill is limited (this is what microbiologists term “spectrum of activity.”)

The next issue is that the antibiotic is still a long way from the clinic, and has to undergo a series of rigorous human clinical trials before reaching the pharmacy shelves. This will be a matter of years, not months.

Following this, the mainstream media have presented the antibiotic as being somehow super-resistant, as if to imply that no bacterium in the future will be able to develop resistance against it. This is palpable nonsense. No one knows, and the prevailing microbiological theory is that one day a bacterial species will develop resistance. This is why the search for new antibiotics needs to be continuous. In relation to this, the study notes that the new antibiotic has a similar potential for resistance to vancomycin. All well and good, however, evidence is pointing towards vancomycin resistance by bacteria being very possible within the next few years.

To finish up, I am excited by Teixobactin. I think it does present a step forwards. However, we should not see it is the answer to all of society’s medical bacterial concerns. Far more research is needed and far greater prudence on the part of farmers, medics and patients is required in limiting the use of antibiotics to only the most serious of relevant infections.

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