Treatment-resistant bacteria threat rises: What are the options?

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Treatment-resistant gonorrhea threat rises in North America
Treatment-resistant gonorrhea threat rises in North America
By Julie Steenhuysen – Reuters.Com Jan. 8, 2013

Treatment-resistant gonorrhea threat rises in North America | Reuters.
A Reuter’s article today again illustrates the disturbing trend in our biochemical battle with other species, like the bacteria mentioned in this article–we are losing this war!  In the last few weeks, we have seen a number of articles outlining the discovery, or at least public disclosure, of new superbugs. Here is just a recent listing of articles on some superbugs:

Methicillin Resistant Staphylococcus Aureus (MRSA)

  1. MRSA Superbug Found in British Milk
  2. When Is a MRSA Infection Grounds For a Baltimore Medical Malpractice Lawsuit?
  3. Battles that still need the attention of the media

 Klebsiella pneumoniae carbapenemase (KPC)

  1. Klebsiella pneumoniae Carbapenemase-producing Enterobacteria in Hospital, Singapore
  2. The KPC Killer

NEW AIDS-like Virus

  1. New HIV-Like Virus in China
  2. Highly Contagious AIDS-Like Disease Spreading in China
  3. Highly contagious mystery virus with AIDS-like symptoms quickly spreading  throughout China

Necrotizing Fasciitis – Group A Streptococcus Disease (GAS)

  1. Mechanic has arm amputated after small cut on his hand develops into flesh-eating disease
  2. Talked-about stories of 2012 still vivid
  3. Lesley Clark’s Survivor Story

General Articles

  1. How hubris put our health at risk – CNN
  2. Three Scary Charts On The Post-Antibiotic
  3. Growth Factor: How Bacterial Infections Persist through Antibiotics [Video]

We are losing the battles

The overall message is that we have been losing the biochemical war that we have been waging against these pathogenic human predators for years.  The laws of natural selection work both for us and against us, and in this case are working very strongly against us.  The more we rely on biochemical weapons to keep these species at bay, the more susceptible individuals live and reproduce more susceptible offspring.  At the same time, the more we use our weapons against these pathogens, the more they become resistant as the strongest survive and reproduce stronger offspring.
Another problem that we face is that the new chemistries we are developing to attack these bugs brings with them higher risk and more side effects.  Many of our magic bullets like penicillin, streptomycin, and tetracycline, to name a few,  are no longer effective.  We have, for almost 50 years, been computer modeling every possible known chemistry to fight diseases and these models have yielded great results in the past.  The current problem is that the low hanging fruit, the drugs with low side effects, are long since discovered, the bacteria have become resistant,  and the drugs are no longer very useful.  Now, we are mining the ones with “reasonable” or manageable side effects.  Soon, we will be left only with options that have significant side effects that will require custom fitting of our individual chemistry–our individual phenotype and genotype–in order to avoid dangerous or fatal side effects.

Can we win the war?

Unfortunately for us at this time, there are limited alternatives. But there are some options remaining that offer new hope–at least in the short term. One area of exploration is finding new techniques to increase the efficacy of older drugs that are no longer effective due to limitations of dosage based on prior methods of delivery.  Historically drugs have been delivered in three main ways: Topically (by application directly to the site of the infection), by ingestion (through the mouth, nose, or suppository), or by injection into the muscle or blood stream. The latter two, methods historically have provided the only method to reach the inside parts of the body and have had a number of physiological factors limiting the dosage that arrived at the site of infection.
Some parts of the body, where infections can occur, do not get good blood or fluid flow.  Ingested and injected drugs get disbursed throughout the entire body so only small amounts get to any one part.  Many of the drugs we have developed have had internal dose limiting side effects like toxicity to stomach, liver, kidneys, etc. Others, have had overall dose limitations due to general toxicity or irritation to the tissues they pass through like the walls of our blood vessels. Overall, this means that in the past the effective doses that we could deliver to an affected area were often only marginally effective in the first place.

Some new hope on the horizon

There are new technologies by companies like Savara Pharmaceuticals who are taking older, so called orphan drugs, and developing methods to introduce those drugs in a internal topical manner significantly increasing the effective dose while bypassing the potential side effects. Savara is working on using an older drug, Vancomycin, and applying it directly in the lungs to help Cystic Fibrosis patients with MRSA effectively fight this dangerous and often fatal infection.
Another interesting company is ViThera Pharmaceuticals who is working on methods to use genetic engineering to alter the chemical production of normal gut flora (bacteria like lactobacillus) to produce beneficial therapies right at the site of the problem.  In ViThera’s case, their initial approach is to treat Inflammatory Bowel Disease (IBD) and potentially Crones Disease–two rapidly rising problems in America–and currently very expensive to treat.
Both of these programs have one thing in common.  They are attempting to find new ways to significantly increase the dose of the chemistry needed, directly to the site of the issue, while minimizing or eliminating the impact on other tissues, or the rest of the body.  While bacteria have developed resistance to our prior treatment options, the resistance is based on the limited doses that could be delivered at the time. In most cases, it has been shown that a massive dose can be completely effective.  These new delivery technologies, in effect, hold the promise to allow for the delivery of overwhelming levels of therapeutics completely destroying the pathogenics.  These are one area of development that hold the potential for great and rapid promise.

New research – new methods

Another key area of research is the discovery of the physio-chemical methods that organisms like bacteria use to become resistant. This article by Sean S. Kardar entitled, “Antibiotic Resistance: New Approaches to a Historical Problem” is a good source to understand the problem and current research. While many stories emphasize the overuse of antibiotics, such as in livestock, foods, and over prescription as the leading cause, this is likely too simplistic an answer.  There are many potential practices that lead to resistance. Part of the problem, as we spoke about above, was the natural selection of more resistant strains due to the inherent dose limitations of older delivery methods. Another key area is our own human behavior.  We just don’t take all the pills we are supposed to for a variety of reasons, and some of the organisms who are stronger–more resistant–survive and reproduce stronger organisms.
Understanding the physio-chemical methods that increase resistance are yielding discoveries in how the resistance comes to be in the first place. Recently, it has been discovered that at least some bacteria in effect go to sleep and stop reproducing, other research shows that bacteria can modify the walls of their cells so the antibiotics can’t stick. See this reference, “Scientists discover new method by which bacteria become resistant to antibiotics“.  Discoveries like this are illuminating the path to new treatment strategies as seen in this article, “Method Seems to Attack Bacterial Resistance” where researchers are finding ways to turn off the genes in the bacteria that lead to resistance. So there is some hope, at least for the short term!

The laws of natural selection seem immutable–but, maybe not!

Overall the future of our biochemical warfare with other species still appears to point to our eventual loss but we are an inventive and dynamic species. Perhaps we will one day yet discover the ultimate answer, even though natural selection would indicate this is a very remote possibility. Regardless of how bleak the future can look we still have no acceptable alternative but to continue to use biochemical warfare to preserve ourselves, and to seek other strategies to continue to buy our species more time on the planet!

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