June 2011 – Antibiotic Fail

New, Killer E. coli Strain O104:H4

The German outbreak of E. coli last week killed at least 26 people and made news headlines around the planet – it was the deadliest E.coli outbreak ever recorded, as well as many hundreds suffering kidney failure. E. coli strains have and will continue to cause deaths, but this particular strain is more worrying. The following quotes are from the website of the AAAS Science magazine, a no sensationalism zone, and the Wall Street Journal:

…a never-before-seen hybrid, combining the worst of several bacterial strains. …one gene fragment appears to have come from another food-borne pathogen, Salmonella enterica, while other genes are highly homologous to those found in other, phylogenetically distinct E. coli strains, including a strain called O25:H4-ST131. [Science Mag]

The 2001 strain caused fewer than five identified cases world-wide, and scientists never did identify its natural reservoir—where a new strain of the E. coli bug can originate, such as in cattle. But the genetic analysis showed that as the 2001 bug likely swapped genetic material with other bacterial strains, some big changes occurred.

The 2011 version turns out to be resistant to eight classes of antibiotics, including penicillin, streptomycin and sulfonamide. The likely reason is that rapid evolution “resulted in the gain of more genes during the last 10 years” that conferred immunity against many more antibiotics, according to BGI. [WSJ]

The new bug is more deadly, more contagious, and more resistant. In the Weekend Australian, Michael Osterholm was quoted: I’ve never seen this array of virulence and antibiotic resistance. It’s a unique combination. This is the ongoing trend with many bacterial infections, meaning things will only get worse.

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