Vancomycin – now 1000x more powerful

The original form of vancomycin is an ideal starting place for developing better antibiotics. The antibiotic has been prescribed by doctors for 60 years, and bacteria are only now developing resistance to it.

…Combined with the previous modifications, this alteration gives vancomycin a 1,000-fold increase in activity, meaning doctors would need to use less of the antibiotic to fight infection.

The discovery makes this version of vancomycin the first antibiotic to have three independent mechanisms of action. “This increases the durability of this antibiotic,” said Boger. “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”

Read more at: https://phys.org/news/2017-05-antibiotic-bacterial-resistance.html#jCp

MultiDrug Cocktails – A Solution or Tragedy?

The big problem with antibiotic resistance is that we don’t know what is next in terms of solutions. In a few years someone could make a miraculous discovery. Or we could wait decades and all that changes is the number of people dying.

One option is combining multiple antibiotics together, something that has been shown to work. Although the scientists don’t fully understand why it works, it gets results just like multidrugs for HIV.

So there’s a conundrum. It could just work for a hundred years. Or it could work for 5 years and create super-super-drug resistant bacteria that will never be defeated.

I guess the solution is to concentrate on using these products as sparingly as possible.

Story at OZY

 

What price new antibiotics?

While it is remotely possible that there are no more useful antibiotic products to be discovered / created, it seems that the only reason no new ones have been produced is that there is (currently) little chance of profit.

According to New Scientist, the estimated cost of coming up with a new and useful antibiotic is about $2.5 billion. Despite the massive customer base, getting a return from such an outlay is impossible while the market already has off-patent products still selling at low prices.

Here’s the most likely order of events:

  • Big Pharma will avoid antibiotics while cheap, current products are still being sold
  • Public awareness will develop regarding the impotence of current products
  • Big Pharma will work on new antibiotics, and for 5-10 years we will become shockingly more mortal
  • At the same time governments will fund research, and add to the news that we are in trouble
  • Eventually we will either have numerous new & effective antibiotics, or we will go through phases of having useful products and many people dying, or no new antibiotics will be discovered and we are screwed

£10m Longitude Prize to Fight Antibiotic Resistance

The British public voted, and chose wisely from the six contenders for the Longitude Prize (which is essentially funded by national lottery profits).

The fight against antibiotic resistance will be the focus of a £10m fund, it has been announced. Both amateur and professional scientists will be encouraged to try to come up with the solution to the problem of decreasing effectiveness of the drugs as part of this year’s Longitude Prize.

The challenge, one of six proposed, was set by public vote on Wednesday. Scientists are now asked to to come up with a “cost-effective, accurate, rapid, and easy-to-use test for bacterial infections that will allow health professionals worldwide to administer the right antibiotics at the right time”.
[Source: The Guardian]

At least the goal is achievable. To find a new type of antibiotic, the prize would need to be in the hundreds of millions to get big-pharma interested.

Back To Square One / Short LifeSpans

The History of Medicine:

  • 2000 B.C.—Here, eat this root.
  • 1000 A.D.—That root is heathen. Here, say this prayer.
  • 1850 A.D.—That prayer is superstition. Here, drink this potion.
  • 1920 A.D.—That potion is snake oil. Here, swallow this pill.
  • 1945 A.D.—That pill is ineffective. Here, take this penicillin.
  • 1955 A.D.—Oops … bugs mutated. Here, take this tetracycline.
  • 1960–1999 A.D.—39 more “oops.”… Here, take this more powerful antibiotic.
  • 2000 A.D.—The bugs have won! Here, eat this root.

—Anonymous, as cited by the World Health Organization (WHO, 2000a)

A few antibiotic products on the horizon

Four of the six largest pharmaceutical companies (Big Pharma) are not developing antibiotics any more. While almost everyone will use them at some time in their life, people do not use them continuously – and it is the continuously used products that make the most profits. For example, annual sales of cholesterol pill Lipitor are only 10% less than the top five antibiotic products combined. With doctors sensibly being advised to be more cautious and to prescribe less, and resistance growing, Big Pharma sees it as a declining market.

Up until the mid-70s ten different types of antibiotic were developed. Since then, all new antibiotics have been derived from existing products – they’ve just patched them up so that they’ll work again. Resistance arises quickly. This means that our only salvation will be new types of antibiotic developed by smaller companies.

Fortunately new products are being developed, with Optimer leading the way with five. Pharma companies Trius and Cubist are also in late-stage trials.

Full story is at Bloomberg.

FDA: A Major Hurdle

While the USA is not the only country where new drugs are developed, they are a major force. The current development landscape means that drug companies concentrate their efforts on drugs that will provide the biggest ROI, and with the least impediments. The wider the application (as with antibiotics), the greater the chance that some potential users will have an adverse reaction. Which means even more testing.

A recent Forbes article, How the FDA May Kill Millions of Us, says:

Antibiotics easily conquered such illnesses as pneumonia and tuberculosis, which routinely killed countless numbers of people each year. Bacteria, of course, can become drug-resistant, but for decades pharmaceutical companies, especially in the U.S., routinely came up with new antibiotics to fell new killer germs. Now, however, the flow of new stuff has dried to a trickle.

In Antibiotics: The Perfect Storm (Springer, 2010) David M. Shlaes lays it out. “Regulatory agencies like the FDA are contributing to the problem with a constant barrage of clinical trial requirements that make it harder, slower and more costly to develop antibiotics.

In fact, Pfizer, the largest pharmaceutical company in the world, has ceased all development on antibiotics. A timeline over at Wikipedia shows how bad the situation has become. Whereas in the past multiple new antibiotics were released every year, in the last decade there have been just five:

1992 – fleroxacin
1992 – loracarbef
1992 – piperacillin/tazobactam
1992 – rufloxacin
1993 – brodimoprim
1993 – dirithromycin
1993 – levofloxacin
1993 – nadifloxacin
1993 – panipenem/betamipron
1993 – sparfloxacin
1994 – cefepime
1999 – quinupristin/dalfopristin
2000 – linezolid
2001 – telithromycin
2003 – daptomycin
2005 – tigecycline
2005 – doripenem
2009 – telavancin

http://en.wikipedia.org/wiki/Timeline_of_antibiotics