6 ms·
Teixobactin is cool, but if it's only active against gram positives, it's never going to work against most of the bacteria listed in the article: E. coli, Salmo
by pak 10y ago
Teixobactin is cool, but if it's only active against gram positives, it's never going to work against most of the bacteria listed in the article: E. coli, Salmonella, Klebsiella, N. gonorrhoeae, etc. Most of the terrible new drug resistance genes are showing up in gram negatives.
Sure, new methods of finding antibiotics are in the works, although the article you link has plenty of experts recommending caution about their potential. The bigger point is that in 2016 there is a looooooong road from antibiotic "candidate" to FDA-approved drug. That road involves decades of trials and costs billions of dollars per approved drug.
The larger problem is that there is little if any incentive for pharma companies to invest in antibiotics compared to traditional blockbuster drugs that are supposed to be taken chronically (and therefore have better ROI). It's the same reason little R&D goes into making new vaccines. It doesn't matter how many candidates are found if they can't make it to market in a timely fashion (the point of the CDC bar graph), and this is what the "slow catastrophe" really is. It is not that scientists will never figure out new ways to kill bacteria.
- drzaiusapelord 10y ago>That road involves decades of trials and costs billions of dollars per approved drug. Only because we've had time as a luxury in the past. I imagine new variants will get fast tracked. FDA bureaucrats hoping to lazy their way to retirement will be under a lot of pressure to actually get things done quickly when there's so much social need. No one wants to be the POTUS who didn't fast track life saving antibiotics if they're shown to be generally safe in early testing. The FDA is a government organization and as such is subject to the politics of our leadership and indirectly, the electorate. The FDA has a page about this process here: http://www.fda.gov/forpatients/approvals/fast/ucm20041766.htm http://www.fda.gov/forpatients/approvals/fast/ucm20041766.ht... At least 774 drugs have gone this route: http://www.bmj.com/content/351/bmj.h4633 http://www.bmj.com/content/351/bmj.h4633
- djschnei 10y agoAm I the only one that would prefer that politics and lazy bureaucrats didn't have the ability to get in the way of my well being in the first place?
- nnf 10y agoNo.
- djschnei 10y agoOh, good.
- iheartmemcache 10y agoIt's not as easy as that. Take the meat/poultry/milk products industry. In the EU, legislators have done a net-good for humanity by aggressively issuing legislation restricting antibiotics and growth-hormones. This is widely accepted as good for humanity as evidenced in this seminal article[1]. The sword cuts both ways. [1] http://jac.oxfordjournals.org/content/53/1/28.full http://jac.oxfordjournals.org/content/53/1/28.full
- ceejayoz 10y agoSee also: vehicle safety features like airbags, seatbelts, crumple zones, child car seats, safety testing, etc. Collectively, they've helped drop car crash injuries and fatalities enormously.
- djschnei 10y agoBecause humans, without regulation, don't value vehicle safety. Gotcha. See also: https://en.wikipedia.org/wiki/Totalitarianism https://en.wikipedia.org/wiki/Totalitarianism
- ceejayoz 10y ago> Because humans, without regulation, don't value vehicle safety. Gotcha. Basically. Humans are horrible at cost/benefit calculations on an abstract level that may not directly affect them for years or even ever on an individual scale. I've known people who won't wear seatbelts because someone they know got trapped by one in a freak accident, despite overwhelming statistical evidence that's a dumb approach. The industry also has a long history of fighting regulations that require safety features but make cars more expensive. http://www.nytimes.com/1986/07/20/weekinreview/the-give-and-take-on-seat-belt-rules.html http://www.nytimes.com/1986/07/20/weekinreview/the-give-and-... > Last month, Ford proposed weakening the transportation department's 1984 rule in exchange for faster introduction of air bags in its cars. The company offered to install the bags on the driver's side of a majority of its cars by the 1990 model year if the department would drop its requirement that the front seats of all cars be equipped by then with automatic or so-called passive belts, designed to restrain the passenger as the car door closes. http://blog.esurance.com/seat-belt-history/ http://blog.esurance.com/seat-belt-history/ > A Federal Motor Vehicle Safety Standard proposes that all vehicles made after January 1, 1973, include an automatic restraint system, i.e., air bags or automatic belts. The auto industry, knowing that it would have to increase production costs to meet the new standard, balks, leading to a decade of argument and delay. https://en.wikipedia.org/wiki/Unsafe_at_Any_Speed https://en.wikipedia.org/wiki/Unsafe_at_Any_Speed etc.
- busyant 10y agoI used to work at an antibiotic discovery startup. I used to joke that there were so many groups with a Gram+ antibiotic drug discovery program going that my parents were probably running one out of their cellar. Gram- are tough.
- mrfusion 10y agoSay are there any compounds that fight only gram negative and leave positive untouched? I'm thinking that might be useful for periodontitus?
- busyant 10y agoMany antibiotics classes seem to be partially selective at killing either Gram+ species or Gram- species. For example, fluoroquinolones can kill both Gram+ and Gram- microbes, but they are generally better at killing Gram-. Other classes have the reverse characteristics. I don't know much about the types of microbes that cause periodontal disease. However, my company was initially interested in treating Community Acquired Pneumonia (CAP). The problem with CAP (and many other bacterial infections) is that they can be caused by either Gram+ or Gram- pathogens. This means that if you're making a drug to treat CAP, you need an antibiotic that can "hit" both types. A common occurrence when we were looking for a candidate drug that could treat CAP was that the candidate would be powerful at killing Gram+ CAP microbes and weak at killing Gram- CAP species. If we improved the drug's ability to "hit" Gram- species, we would always seem to lose potency against Gram+. It was extremely tricky to find something that was powerful enough against _all_ the relevant microbial pathogens.
- Fordrus 10y agoAn antibiotic discovery startup, eh? That's freaking fascinating, I'm in bioinformatics myself, I'd love to hear more about this- I wasn't aware that an antibiotic discovery startup was/is/could be a thing at all- If you can tell me anything more or put me on the right track to reading more about your old employer in that space or whatnot, I'd appreciate it! :)
- 10y ago
- JunkDNA 10y agoYou're right about incentives being wrong, but I disagree with the preference for chronic drugs being a primary factor. In my opinion, the primary incentive killer is that agencies like the FDA will not approve a truly new antibiotic for general use. It gets approved as an antibiotic of last resort. So for the time that a new antibiotic is under patent protection, the company can't recoup their R&D because they can only address a tiny part of the market. When the day finally comes when the wonder drug can be standard of care, it's well off patent and generic competition torpedoes any real profit. Why develop a great new antibiotic if the FDA forces you to keep it locked away? From the company perspective it makes no sense.
- pak 10y agoHmm, well as a counterpoint to your point about the FDA, fidaxomicin was approved in 2011 for general use against C. difficile colitis, because it showed certain outcomes that compared favorably against the current standard of care (oral vancomycin) [1]. The reason it isn't used more often is probably because it is one of the most expensive antibiotics available. Antibiotics aren't typically approved only as "last resort"; it remains at the discretion of the physician to jump straight to the big guns before drug susceptibility test results are available (which is part of the problem). [1] https://en.wikipedia.org/wiki/Fidaxomicin https://en.wikipedia.org/wiki/Fidaxomicin
- JunkDNA 10y agoYou're right about incentives being wrong, but I disagree with the preference for chronic drugs being a primary factor. In my opinion, the primary incentive killer is that agencies like the FDA will not approve a truly new antibiotic for general use. It gets approved as an antibiotic of last resort. So for the time that a new antibiotic is under patent protection, the company can't recoup their R&D because they can only address a tiny part of the market. When the day finally comes when the wonder drug can be standard of care, it's well off patent and generic competition torpedoes any real profit. Why develop a great new antibiotic if the FDA forces you to keep it locked away? From the company perspective it makes no sense.