Advertisement

Rising Plague

The author of a new book on the antibiotic resistance crisis entreats scientific and lay communities for help in the quest for new weapons

By | August 27, 2009

How do you look the family members of a critically ill patient in the eyes and tell them that their loved one is going to die because there are no drugs left to treat their illness? I'm an infectious diseases specialist. I'm not supposed to have to bear such bad news to patients or their families. I expect to cure my patients' infections, and their families and friends hope that I can. It's been that way ever since the 1940s, when penicillin burst onto the scene. But this is the 21st century, and things are different now.
The discovery of antibiotics in the mid 20th century was nothing less than a revolution in public health and medicine. It was a revolution as significant to human civilization as the discoveries of Isaac Newton or Thomas Edison's first light bulb. Physicians trained in the era immediately preceding the dawn of antibiotics learned how to resign themselves to the fact that they could not change the course of their patients' illnesses in most cases. Their job was largely to make an accurate diagnosis so they could relate the unalterable prognosis to the patient. In an instant, antibiotics changed all that by empowering physicians to eradicate diseases with aplomb. What a stunning power to acquire! How ghastly then, having acquired this brilliant power, to watch helplessly as it shrinks back into history, leaving us once again at the mercy of even the most mundane microbes. That's the reality that we're facing now. linkurl:__Rising Plague__;http://www.prometheusbooks.com/index.php?main_page=product_info&cPath=57_187&products_id=1932 is a fervent plea -- in the words of the poet -- that we not let antibiotics "go gentle into that good night." In my latest book I describe how the relentless escalation of antibiotic resistance has created a critical need for new antibiotics. Just when we need it most, the discovery and development of new antibiotics is dying. I share with you real patient stories to underscore that the loss of effective antibiotics is not a hypothetical problem. Antibiotic resistance is killing thousands of people every year, and devastating their families. I know this because I have seen it first-hand. The antibiotic problem didn't take shape overnight. And one can't blame physician misuse of antibiotics for all of our problems. Despite how widespread that belief is, it does not reflect reality, and it serves as a poor foundation for effective response planning. We instead must alter our worldview of antibiotics and bacteria. Bacteria have been creating and defeating antibiotics for 20 million times longer than humans have known of the chemicals' existence. We will never stop antibiotic resistance from occurring. Efforts to conserve antibiotic use can help slow down the spread of resistance. But, ultimately, focusing all of our energies on conserving antibiotics will only delay the inevitable exhaustion of effective antibiotic resource. Rather, what is needed is a comprehensive response strategy that includes continued efforts to conserve antibiotics combined with efforts to replenish the resource by reinvigorating the discovery and development of new antibiotics.
"...with today's [antibiotics] it is possible to place in the hands of a barefoot, nonliterate villager more real power to affect the outcome of a critically ill [patient] than could have been exerted by the most highly trained urban physicians of twenty-five years ago."

-- From W. McDermott, et al. "Introducing modern medicine in a Najavo community." Science, 131:197-205, 1960.
The problem here is not scientific. New antibiotics are dying before they have a chance to enter the marketplace due to a murky regulatory landscape and also due to unfavorable economics (i.e., the relatively low rate of return on investment afforded by sales of short-course antibiotics compared to sales of drugs for chronic conditions, such as hypertension, dementia, cancer, arthritis, and high cholesterol). Big Pharma has largely exited the scene. Some biotech companies have picked up the torch, but many are already out of business due to their inability to get antibiotics approved. The US Food and Drug Administration rejected the last eight antibiotics that have been proposed for approval. It is truly ugly out there for antibiotics. We must stop being myopic and complacent. Miracle drugs will not fall from the sky when we need them. If we want to continue to live in an "antibiotic era" -- a unique, 74-year-old interval in the five-thousand-year annals of medicine -- we must act now. If we do nothing, we run the risk of inviting a bleak "post-antibiotic" future, in which infectious diseases once again reign supreme. I wrote __Rising Plague__ because my colleagues and I need your help. This crisis will not be averted without your support, without a grassroots movement to put pressure on all sides -- political, medical, pharmaceutical, and consumer -- to band together to act. I will tell you what can be done, but we need your help to do it. linkurl:__Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them__,;http://www.amazon.com/Rising-Plague-Bacteria-Dwindling-Arsenal/dp/1591027500 by Brad Spellberg, MD, Prometheus Books, Amherst, New York, 2009. 264 pp. ISBN: 978-1-59102-750-8. $26.00 US. linkurl:__Brad Spellberg;http://www.harboruclamed.com/Faculty/spellberg.html is associate professor of medicine at the David Geffen School of Medicine at UCLA and is based in the Divisions of General Internal Medicine and Infectious Diseases at the Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center. He was featured on an Emmy-award-winning episode of __NOVA__ called "Rise of the Superbugs."__
**__Related stories:__***linkurl:Gut harbors antibiotic resistance;http://www.the-scientist.com/blog/display/55928/
[27th August 2009]*linkurl:The Microbial Health Factor;http://www.the-scientist.com/article/display/55864/
[August 2009]*linkurl:Mysterious resistance;http://www.the-scientist.com/article/display/54963/
[September 2008]
Advertisement

Comments

Avatar of: PAUL STEIN

PAUL STEIN

Posts: 61

August 28, 2009

It was stated that, "The US Food and Drug Administration rejected the last eight antibiotics that have been proposed for approval." It would have been nice for the author to state the reasons why. To understand how we all must band together, we all must know what the pinchpoints and roadblocks are so that we may most judiciously move our efforts and capital.
Avatar of: null null

null null

Posts: 2

August 28, 2009

You could start by persuading your publisher not to be such a tightwad and to release the TOC etc to Amazon.
Avatar of: MORGAN GIDDINGS

MORGAN GIDDINGS

Posts: 11

August 28, 2009

There is little funding right now for antibiotic resistance research. Much of the microbial-related research money is directed towards biodefense, virus research, and other issues, so there is very little left over for antibiotic resistance. I know, I have tried, based on novel discoveries about the first steps of drug resistance in P. aeruginosa. There are no special calls for proposals in antibiotic resistance, so those proposals go in and fight it out for rare funding against everything else. With persistence, we may eventually get it funded, but the struggle isn't worth it to me - my other research areas are much easier to get funding in, because it isn't so cutthroat. So I am giving it up, for now.\nThere seems to be a big blind spot for this issue at NIAID (the institute at NIH that funds most microbial-related work).\nThe prognosis is not good.
Avatar of: Mike Breeden

Mike Breeden

Posts: 4

August 28, 2009

Shortly after penicillin was discovered, resistance to it was discovered. Really though, there is another way to look at it as the author did, it's an evolutionary thing. Lets see. Add up the ecological factors... Disease has always ruled humans, add population density increase, add mobility, add the increased cost of raising children in a technological society - the sum is we are in deep trouble. I instinctively (logic) figured that out, oh lets see, that was 38 years ago. It took me about 15 years to solve that problem, but it is only part of something bigger. We are entering a new ecology, but are still adapted to the previous one. In that sense it is as much a moral problem as a scientific one. How do we adapt genetically and behaviorally to a new niche? Disease is just part of it, even if perhaps one of the hardest and most immediate. It's a tough problem, but it's mostly answered at http://www.diver.net/seahunt/p/p_trans.htm.\nIt answers a lot of other tough problems as well.\n...\nDon't let anything new throw you, it's all new and so novel that it's hard not to object, but I covered it all and answered all the problems.\nDon't let anything weird (at the end) throw you, it is just where I was exploring last.\nI've just started another (say number 15) re-write, but the first half is certainly done. Know any bored publishers?\n--You have to have a hobby, but an obcession will do.--\n\n\n\n\n\n\n\n
Avatar of: anonymous poster

anonymous poster

Posts: 3

August 28, 2009

It's interesting that ~60% of Americans don't believe in evolution. Since they don't believe that bacteria evolve, drug resistent bacteria can't exist (but obviously they do exist). \n\nIt's disturbing that so many people fight the teaching of science in school. Understanding evolution is key to trying to stay ahead of constantly evolving bacteria and viruses. \n\nWe can eliminate evolution from our schools and be back in the dark ages of fighting disease.
Avatar of: anonymous poster

anonymous poster

Posts: 1

August 28, 2009

As I microbiologist I must take exception to the superficial blow-off of the problem of physician mis-prescribing of antibiotics. The problem is well documented--see for example the web site of the Alliance for the Prudent use of Antibiotics. http://www.tufts.edu/med/apua/ While physicians aren't the only ones to blame, they are certainly a major force in sending antibiotics "into that good night." The emergence of antibiotic resistance may be inevitable, but the rate of emergence has been accelerated by orders of magnitude by the profligacy of prescribing by today's physicians. Providing more antibiotics to those who misuse what we already have cannot be the major answer. \n
Avatar of: RON HANSING

RON HANSING

Posts: 20

August 28, 2009

New paradigm out of box thinking.\n\nOne solution is of course federal funding to Universities as opposed to Big Pharma dependency.\n\nBetter yet, maybe we need to think out of the box. So often, scientific knowledge hinders original thinking, (such as the concept that there are no pathogens in the stomach, or reverse transcriptase is not how RNA viruses replicate.)\n\nHelicacobactor and reverse transcriptase, used hundred year old technology. (Culture and substrate subititon and looking for a reaction via an unknown enzyme. \n\nAll it took was for someone to have the crazy idea... and they received the big prize.\n\nHow can we convert pathogens to commensal organism??? What is it in the mouth that inhibits infections when we get a cut in the mucosa? \n\nBegin with any absolute crazy idea, an idea, us older guys will say, ?That ridicules in an attempt to ?keep the younger guys from trying crazy ideas by exerting our power over creative ideas.\n\nAnd of course, this requires funding young scientists liberally, without whatever ?stupid? idea they want to pursue.\n\nToday we are stuck in the antibiotic paradigm? and any other crazy idea is snuffed out by the money people? Let freedom ring? take chances? pursue and fund crazy ideas, perhaps is the approach we should have.\n\nLastly, as with most scientific breakthrough, invariably comes from the young. I?m too old to be creative, and sadly, fixed old fashioned ideas? But I?m willing to fund crazy ideas, Yes, only a few will pan out. \n\nSome researchers will spend their life and find nothing, and it would be expensive? But invariably, someone will cross that threshold? and create a whole new field of science.\n\nRon Hansing, M.D.9.28.9 \n\n
Avatar of: Phil Terry

Phil Terry

Posts: 5

August 29, 2009

Brad Spellberg makes a passionate if imperfect plea to fix an important and rising problem: resistance to antibiotics.\n\nI welcome books like Brad's written for the general reader that attempt to lay out these important public policy issues.\n\nAt the same time, I agree with the commenter who said we do need to do something about the fact that the majority of the American public does not understand the link between evolution and antibiotic resistance. \n\nThat's why a ragtag group of volunteers has gotten together to produce a Darwin150 lecture series, Facebook campaign and reading groups on Darwin's "Origin of Species" - all free and all available online.\n\nBooks like Brad's along with phone-based reading groups on "Origin" could have a real impact on an adult's understanding of the issues. The free reading group sign-up is here. \nhttp://Darwin2009-1.Eventbrite.com.\n\nShare it with anyone you think would be interested.\n\nAnd I've posted a link to this article on the Facebook page (where we have about 250,000 members and hope to grow to 1 million in time for the 150th anniversary November 24).\n\nThanks!\n\nPhil \nCreator, Darwin150 Facebook campaign and lecture series\nOn our way to 1 million, help us get there\nhttp://www.facebook.com/group.php?gid=53320310123 \nhttp://www.Darwin150.org
Avatar of: anonymous poster

anonymous poster

Posts: 8

August 29, 2009

The Barnes & Noble website has a Table of Contents + a couple of reviews. Amazon still has nothing.
Avatar of: Robert Pytlik

Robert Pytlik

Posts: 7

August 30, 2009

I have not read the book and I hope it will deal also with topics that could not apparently be covered by the short article. Working as a clinical hematologist/oncologist, I am facing the problem of antibiotic resistance almost daily. Therefore, I would like to point out several issues, which should be kept in mind:\n- first, there is definitely a difference in resistance between "street" strains of bacteria and nosocomial ones. Patients who have been infected out of hospital have less frequently resistant infection (unless, of course, they were previously colonized by a nosocomial strain). Therefore, one of the simply measures how to fight resistance is to keep patients in hospitals only if it is absolutely neccessary.\n- second, the resistant nosocomial strains need a place to survive outside patients. These places might be not only medical devices, as respirators or air humidifiers but also climatization units and even the buildings themselves (some molds). We need better cleaning algorithms for these devices, we need them to be equipped with easily replacable parts possibly covered by antimicrobial films or other materials and generally to make our simple hygiene measures more efficient. \n- third, as in other parts of human life, certain antibiotics are fashionable and others fall out of favour. Broad-spectrum cephalosporins and quinolones are currently responsible for a huge increase in resistant strains. But on the other hand, the old and sometimes almost forgotten antibiotics (e.g., chloramfenicol) keep very good sensitivity profile. You can argue that the chloramfenicol problem was the risk of fatal aplastic anemia, but this risk is about one in 30 000 patients. So what is more acceptable: to watch one patient say, in each 100, to die from infection or to risk that one patient in 30 000 will acquire (today potentially curable) aplastic anemia?\n\nThe evolution case: Yes, bacteria do evolve, but we have to keep in mind that any resistance mechanism (extra gene or extra plasmid) needs an extra energy. Therefore, bacteria use these mechanisms only when they are under selective pressure. If they are not, they are replaced again by sensitive ones, which need less energy to keeping themselves alive and multiplying. Nature is very ergonomic.\n\nThe last thing I fully agree: the regulatory issues. A lot of people possibly think only about the positive side of the regulations - safer and more effective drugs. However, the administrative procedures for drug approval cost money and disadvantage the small players with possibly smart ideas but insufficient fundings. I hope that regulatory bodies will not ultimately kill us all by suspending drugs that are vitally needed only for some bureaucratic reasons. As at the end, it is our elected representatives who make the rules, perhaps it would be good to ask them to make the regulatory procedures more flexible.\n

August 30, 2009

Well, I am scientist as all or most of the people who wrote a comment in this history are. It is really something to worry about, I agree and we all know all that the rate of evolutionary change is rather large in a bacteria as compared with humans due to its lower time of life span. Well, some of the commenters are discussing about what happens in the human body when it is attacked by bacteria. We have our own protection system against bacterial infections. However, it is well know that somebody under too much stress have the tendency to get sick, (I remember I got sick when I was about to take the preliminary examination during my Ph.D. program at PURDUE). So, the important issue here is perhaps to understand better our own defenses and find the way to potentiate them. One possibility is to learn to control our emotions and avoid the negative effects in the immune system. Perhaps with this we will be able to reduce the infections and therefore to reduce the indiscriminated use of antibiotics. A happy persons usually does not get sick so often as a person with a depression or under too much stress. Emotional control is something that most of the people does not know.
Avatar of: Hilary Butler

Hilary Butler

Posts: 15

August 30, 2009

I've not had any antibiotics now, for 30 plus years. How did that happen? At the age of 19, I became allergic to the then range of antibiotics. As years passed, every new one tried, attempted to kill me, some in slower ways than others. \n\nWhy is that so important? Because my life as a child, had been one succession of infections after another. Being brought up in the generation that always hammers nails in with the best hammer, out came the antibiotics, all.. the... time.\n\nNot long after it was pronounced, with a shrug of their shoulders, that I was "on my own", it was discovered I had an immunodeficiency.\n\nWith nothing left, of any use, so started a journey of discovering how to survive without antibiotics. I discovered how so many of us carry these bacteria and they do no harm to most. Why do they harm some? I discovered amazing things about how some classes of commensal bacteria keep other more serious classes in check. And how might that be assisted? After all, it was a revolutionary approach for me to see that actually, bacteria and other commensals are there to help, not to hinder.\n\nHow was it, that I'd so regularly got sick? That was when it dawned on me, from my medical records, that it was actually the antibiotics, which started a cyclical downward spiral.\n\nIn randomly "nuking" whatever bacteria was around with nonspecific hammers, every time I'd had a course of antibiotics I was inching towards a bigger problem.\n\nI changed my focus to the older histories of the uses of yoghurt, kefir, matsoni, and other probiotic based natural foods. I looked at what real health was, rather than the absense of pathologically defined sickness as being the "norm".\n\nAnd today, I can still tell the tale. Who knows when, and of what I will die. That I defied the depressing forcasts of the infectious experts is enough for me.\n\nPerhaps, instead of looking for another better bigger hammer, eyes should be cast along with Mazmanian (the microbial health factor), on the purposes of commensal bacteria; how they work together, and harnessing them to fix the problem, which every year, is made worse, and more serious by the continued blanket use of antibiotics in the first place.\n\nOther research should look at how, when antibiotics are used, the doctors who prescribe them, return the commensal flora back to where it was before they lobbed in the first anti bacterial incendiary.\n\nJust maybe, then, real progress will be made.
Avatar of: Carol Mershon

Carol Mershon

Posts: 4

August 31, 2009

Could technology be behind the increase in antibiotic-resistant microbes? More specifically, could chronic exposure to man-generated electromagnetic, microwave, and radiofrequency radiation be behind the surge in antibiotic resistance in recent decades? Think cell phone and wifi towers and antennas, cell phones, cordless phones, etc..., and read these...\n\nMobile Phone Emissions Increase Worm Fertility:\n\nhttp://www.newscientist.com/article/dn1889-mobile-phone-emissions-increase-worm-fertility.html\n\nDo EMFs Affect Yeast Growth?\n\nhttp://www.usc.edu/CSSF/History/2006/Projects/J1310.pdf\n\nThe Effect of Microwave Radiation on Fruit Mold:\n\nhttp://www.usc.edu/CSSF/History/2008/Projects/J1403.pdf
Avatar of: anonymous poster

anonymous poster

Posts: 4

August 31, 2009

Firstly, to address one piece of slightly erroneous information:\n\n"The evolution case: Yes, bacteria do evolve, but we have to keep in mind that any resistance mechanism (extra gene or extra plasmid) needs an extra energy. Therefore, bacteria use these mechanisms only when they are under selective pressure. If they are not, they are replaced again by sensitive ones, which need less energy to keeping themselves alive and multiplying. Nature is very ergonomic." by Robert Pytlik\n\nThis is not strictly true. It was long held that if the selective antibiotic pressure were removed from a population that they'd revert to a sensitive state; this simply is not what is actually observed. Any fitness cost that is incurred by the addition of a mobile genetic element is often ameliorated by a concomitant mutation elsewhere (a nip-tuck) that restores its comparative fitness with the wild-type. \n\nIn addition, gene silencing as been observed in cases where selection is removed, simply deactivating the resistance gene at the transcriptional level, but which can be activated at a later date. More evolved resistance mechanisms such as ermC (erythromycin) and cat (chloramphenicol) are inducible, thus a stable mRNA transcript, with an free ribosome binding site, is only available in the presence of the antibiotic to which the transcript confers resistance.\n\nI have worked as a researcher on mechanisms of transfer of antibiotic resistance, and mechanisms of action of antibiotics for the better part of a decade. The poor funding in the is area has resulted in myself, and many other researchers in the field, having to leave this research area. \n\nIf and when funding bodies/government/pharma come to their senses and stop trying to make profit from antibiotics (they'll never yield as much as lifestyle drugs), then they may well find that an entire knowledge base of researchers will have moved on, which is a shame.
Avatar of: Camilo Colaco

Camilo Colaco

Posts: 10

September 1, 2009

The genetics of evolution mean that development of antibiotic resistance is only a matter of time. The best strategy to combat resistance must surely be the development of effective vaccines as this pits the evolving immune response against the evolving pathogen.\n
Avatar of: anonymous poster

anonymous poster

Posts: 3

September 1, 2009

The call to have gov't supported research is on-point. While I'm a free-marketer, the free market doesn't work with antibiotics. If you create a totally new class of antibiotic and sell it ethically, you're selling to a tiny fraction of a very small market. \n\nTo contrast, patients take cholesterol medications for decades versus antibiotics they take for days. It's very hard to make money with antibiotics and the development costs are high. \n\nThink about the difficulty in running an ethical trial of antibiotic for drug resistant bacteria - how do you show it improves patient outcomes? -how do you find patients? - you may have only hours to decide that a current treatment isn't working. Even if you find patients, how do you prove effectiveness? Who do you use as the control population?
Avatar of: anonymous poster

anonymous poster

Posts: 2

September 16, 2009

Antibiotic resistance is only a problem if you are locked into thinking that antibiotics are the only way of dealing with bacterial infection. But we all know that this isn't true - and that many other treatments are as effective as antibiotics, with the added advantage that they are natural and non-toxic for the most part. For example, and a case in point right now - there are children in hospital with E.coli infections. Mannose - a simple monosaccharide - attaches to E.coli (as every E.coli researcher knows), and blocks the lectin attachments that they make as pathogens. This allows them to be shed through the normal exit routes. \n\nAnd there are natural antimicrobials like wild oregano oil and raw garlic. The medical profession seems to have forgotten all it's accumulated knowledge since the time of Hippocrates. \n\nYes, antibiotics helped, but before the time of antibiotics, knowledgeable doctors could cure just about every infection by boosting the immune system and turning on the body's own natural self-healing, and by giving supplements like iodine, vitamins, sugars (yes, mannose and xylose have been used since the early 1900s), and herbs. It's time the old knowledge was taught again, and doctors became less reliant on antibiotics to make up for a lack of personal knowledge and research. And by the way, for lack of mannose some of the E.coli infected children may die. We need polymath doctors to take charge and fight to get back their inheritance of knowledge, not scaredy-cats who will let children die rather than use a non-approved remedy. \n

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube
Advertisement

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
Advertisement
Mettler Toledo
BD Biosciences
BD Biosciences