From Nature: Antibiotic resistance: The last resort

[GliderGuider]

Urk!

Antibiotic resistance: The last resort

Health officials are watching in horror as bacteria become resistant to powerful carbapenem antibiotics — one of the last drugs on the shelf.

As a rule, high-ranking public-health officials try to avoid apocalyptic descriptors. So it was worrying to hear Thomas Frieden and Sally Davies warn of a coming health “nightmare” and a “catastrophic threat” within a few days of each other in March.

The agency heads were talking about the soaring increase in a little-known class of antibiotic-resistant bacteria: carbapenem-resistant Enterobacteriaceae (CREs). Davies, the United Kingdom's chief medical officer, described CREs as a risk as serious as terrorism (see Nature 495, 141; 2013). “We have a very serious problem, and we need to sound an alarm,” said Frieden, director of the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

Their dire phrasing was warranted. CREs cause bladder, lung and blood infections that can spiral into life-threatening septic shock. They evade the action of almost all antibiotics — including the carbapenems, which are considered drugs of last resort — and they kill up to half of all patients who contract them. In the United States, these bacteria have been found in 4% of all hospitals and 18% of those that offer long-term critical care. And an analysis carried out in the United Kingdom predicts that if antibiotics become ineffective, everyday operations such as hip replacements could end in death for as many as one in six.

Who is it that bats last, again?

[Control-Z]

1. This is frightening

but is there really any behavior or action any one of us can take to prevent it? I ask that honestly. I have kept my and my family's use of antibiotics to a minimum so we would respond better to antibiotics when needed.

I had thought it was the antibiotics that were losing their effectiveness due to overuse. This sounds like it is the bacteria getting stronger leaving little to actually do about it.

[GliderGuider]

2. I think you understand the situation correctly.

Last edited Tue Aug 6, 2013, 04:46 PM - Edit history (1)

We are told that antibiotics are losing their effectiveness due to over-use, which is technically correct but incomplete. The over-use is causing genetic changes in the bacteria, the same way we're seeing Roundup-resistant superweeds. Reducing personal antibiotic consumption will help this just as much as curly light bulbs and cloth shopping bags will help stop climate change.

We really are too smart for our own good... I hate having seen this so clearly. You can't unring that bell though.

[eppur_se_muova]

3. Your last para has it right. This is forced evolution.

Make it tougher for the bacteria to survive, and only the toughest bacteria survive. Remember that Darwin's theory of natural selection was suggested to him (in part) by his observations on the results of selective breeding by pigeon fanciers and the like. No reason it shouldn't work on bacteria -- in fact, since bacteria breed so prolifically, it should work enormously faster. It's especially easy when the trait you're selecting for is simple survival.

[KT2000]

4. Bacteria has been here

longer than we have. They have several ways to evolve to outsmart the antibiotics. Bacteria is capable of sharing with other species of bacteria, the method they have evolved to thwart an antibiotic. It may take several generations to get there but for bacteria, a generation can be 20 minutes.

For perspective on the problem, Dr. Alexander Fleming, the man who discovered penicillin in 1929, informed us that numerous bacteria had developed resistance to it that same year. It was not until World War II that penicillin was developed for commercial use and at that time Dr. Fleming warned that improper use would lead to resistant bacteria. By 1995, ninety-five percent of Staphylococcus aureus was resistant to penicillin. Methicillin was then used in its place. It took about one year for methicillin resistant staph to develop, what we now refer to as MRSA.

[phantom power]

5. Overuse and improper use caused them to lose their effectiveness faster.

Probably a lot faster, although I have no proof of that assertion.

[drm604]

6. And still we continue to add antibiotics to cattle feed.

[happyslug]

7. This includes Gonorrhea but so far NOT Syphilis.

http://www.cdc.gov/std/gonorrhea/arg/

http://www.bloomberg.com/news/2013-07-15/stop-gap-for-antibiotic-resistant-gonorrhea-found-cdc-says.html

http://news.yahoo.com/sex-superbug-meet-antibiotic-resistant-gonorrhea-191743846.html

Stories of "Black Syphilis" have been around since WWII. Sulfa Drugs were effective on Syphilis. but then replaced by Penicillin. The problem was both was neither could penetrate the water barrier around the brain. Tetracycline, developed around 1954 could. Syphilis takes about three months to penetrate the water barrier around the brain. In the days of Sulfa Drugs (pre WWII) and Penicillin (1943-1954) if a person with Syphilis waited till after it had penetrated the brain, all the drugs could do was prevent that person from spreading the disease. The person still had the disease and all of the long term effects tied in with the disease.

I suspect this problem was where the story of Black Syphilis came from, people who waited to long for treatment. The Story should have ended in the 1950s, but some how stayed alive. The story of Black Syphilis retain life as Syphilis. evolved to survive Tetracycline and then other antibiotics.

I have read stories that some strain of Syphilis have evolved to survive all but the last ditch antibiotics of today, and the legend of Black Syphilis has returned (if it ever did go away).

Now some gonorrhea seems to have evolved to be able to survive even the top end antibiotics which is a stop beyond what I have read about Syphilis. While that is "Good News" it is also "Bad news" for Syphilis seems to be following gonorrhea on the track to being able to survive antibiotics. If and when that occurs, we may have to return to treating the symptoms, as was the case before Sulfa drugs.

[NNadir]

8. Carbapenems are a relatively old form of antibiotic, structurally related to, and isosteres of,...

...more or less, the pennicillins, with a sulfur displacing a carbon. (Medicinal chemists do this sort of thing all the time, make substitutions in search of isosteric effects that may increase effectiveness or reduce side effects.)

Although it's unsurprising that bacterial species are evolving resistance to whole classes of antibiotics, it's not a cause for hysteria either.

There are many classes of antibiotics, including the relatively new - and uexpected - class of oxazolidines. Now it is true that Pfizer, for purely business reasons made a huge morally questionable decision to mismanage the original drug of this type, lineazolid - which Pfizer acquired when it bought and destroyed Pharmacia - but the medicinal chemistry of the oxazoline class has not fully been explored, and offers some hope for the future.

There are many other classes of antibiotics as well, and in general there is still very few cases of total cross resistance, we have VREs, MRSEs and other species, but most bacterial infections can, in fact, still be treated.

Pharmaceutical companies are not investing heavily in antibiotics because they actually cure disease, rather than require maintenance doses like, say, blood pressure medications. The latter obviously produce higher returns on investment.

That said, the development of modern structural biology suggests that if properly managed, intelligently pursued, we can produce the tools to keep the bacterial enemies at bay. Many people have noted that we can more effectively revive some old ideas with new insights, for instance the development of new types of phages, although it's impossible to imagine what the stupids in places like Greenpeace, with their hatred and contempt for genetic science that is only mildly less destructive than their hatred of nuclear science, might say about that approach.

The human race is spectacular at improper management and pursuing stupidity at the expense of intelligence. I concede that.

Since becoming a blogger, I've certainly recognized that in spades many times, right here for instance.

However that may be, hysteria and panic will only serve to defeat any effort to address these issues wisely and soberly. The battle against bacterial diseases is not over, it may just be beginning.