Revenge of the Microbes Replay

Last week, I saw a Bloomberg News story that a WHO surveillance program had found that antibiotics “now rank among the most counterfeited medicines in the world” and are contributing to global drug resistance.  It did not reference a WHO report and I was not able to find one which is unfortunate because although the link is logical, data are lacking. If anyone knows of this report, please share the link. The story reminded me of a post I wrote in April 2011:

It’s pretty well known, at least among those in the health care biz, that the problem of antibiotic-resistant, infectious, and deadly bacteria is growing. The problem certainly isn’t a new one (a perspective in the New England Journal of Medicine notes there was concern among docs starting around 1960, Moellering 2011), but the public media’s hysteria last fall about a gene for a new antibiotic-destroying enzyme highlighted another flaw in our drug development system, in addition to ignoring global health diseases (e.g., Boston Globe article).   The gene is called NDM-1 or New Delhi metallo-beta-lactamase-1 and confers to bacteria the ability to destroy beta-lactam antibiotics (e.g., penicillin, cephalosporins, and carbapenems) which are the backbone of anti-infective therapy. More scary is that NDM-1 has been found traveling about with several other genes for beta-lactamase inactivation (e.g., inactivating erythromycin, ciprofloxacin, rifampicin, and chloramphenicol), a gene for a “pump” to flush out antibiotics, and growth factors (for those who don’t remember their microbiology, bacteria have neat ability to share genes by putting them on small DNA loops and injecting them into each other, i.e., sex for bacteria). Even more scary is that NDM-1 was found in multiple types of nasty bacteria and in multiple countries, including India, Pakistan, Bangladesh, Britain, United States, Israel, Turkey, China, Australia, France, Japan, and Taiwan, although there is controversy about the soundness of the studies (Lancet article).   Will NDM-1 get into some easily transmitted and deadly bacteria like those that cause cholera or tuberculosis (which is already drug-resistant to line one and two of our drug defenses), run wild, and kill all humans? I dunno but it looks to me more effort needs to be applied to this global health problem besides using it in a disaster movie script.

Clearly, new antibiotics are needed but, as with the neglected diseases that afflict most of the world outside our expensive medical bubble, the pharma/biotech industry is mostly AWOL and has been for about 20 years. In a classic case of market failure, the problem is that the use of a new antibiotic would likely be restricted to patients who have failed standard therapy (a small number) and, if the drug is any good, used only for a short time, so the pay-back period for the (at least) couple hundred million dollars of R and D could be very long. PhRMA, big pharma’s trade group, doesn’t even mention the lack of antibiotic R and D as an issue (PhRMA issues). According to a Reuters article on the poor pipeline, AstraZeneca and GlaxoSmithKline and to a lesser extent Novartis, Merck, and Pfizer have active antibiotics programs, but the next new drug is about five years away from approval (Reuters article). By my guessimate, there are 10-20 biotechs world-wide with antibiotics programs but most have few drugs in development (e.g., Cubist pipeline).

So what should be done to save humankind from superbugs? There seem to be lots of recommendations but little action. The pharma/biotech industry thinks a clearer FDA regulatory approval and use polices and longer patents will help (Pharma Manufacturing article). The WHO is devoting its 2011 World Health Day to antimicrobial resistance and is recommending a number of solutions (WHO World Health Day policy briefs) which, not surprisingly, are all government-policy-oriented (“commit to a comprehensive, financed national plan”) or, to “foster innovations and research and development for new tools,” are not new and similar to those for stimulating neglected disease drug development: more basic government funding, advanced market commitments, and prizes (not a good idea, see my posting of 12/9/10). The Infectious Disease Society of America has been ringing the alarm bell for more than five years and in 2010 proposed global plan called “10 X ’20: Ten New Antibiotics by 2020” (10 X ’20 Plan). It is short on specifics however, citing only an increased R and D tax credit (like that recommended for neglected disease, see my posting of 3/10/11) and yet another global task force to mount a “man-on-the-moon” effort.

The US government has put money into infectious disease research at universities though the NIH, about $35 billion in 2007 (NIH Report) and the lead institute is the NIAID which has two task forces and sponsors a conference on microbial resistance (NIAID partnerships). And governments and donors are funding half a billion dollars of TB research, some of which is relevant to antibiotics for resistant TB (TDR press release). As for government support of companies which actually may develop a drug, thanks to our government’s pre-occupation with keeping us safe from terrorists, BARDA (Biomedical Advanced Research and Development Authority) has a Broad Spectrum Antimicrobial Program that is funding a few companies with multi-tens-of-millions of dollars (e.g., Achaogen Inc. of San Francisco, BARDA press release).

Are we headed into the perfect storm (c.f. David Dickman’s review of David Shlaes book of that name, Dickman blog) and are we ready for a world without antibiotics (c.f. The Guardian article of that name, Guardian article)? It is clear that bacteria evolve a lot faster than we humans can discover and develop antibiotics, and a lot faster than we invent policies and processes for discovering and developing needed but “uneconomical” drugs in general. So when Johnny and Sally come home from daycare with unstoppable ear infections and end up dead like the millions outside the US that die each year due to lack of medicines for their diseases, maybe we (the public and our representatives) will get serious about drugs for neglected disease.