Image: Peter and Maria Hoey
In Brief
- Dangerous bacteria are developing resistance to existing antibiotics faster than humans can invent or discover new drugs.
- Searching exotic environments and microbial genomes are among the innovative strategies being applied to the problem.
- New approaches that narrowly target single organisms or stop short of killing them may help break the vicious cycle of resistance.
“Superbug Strikes in City” sounds like a horror movie title, but instead it is a headline printed in the October 26, 2007, edition of the New York Post. Twelve days earlier a 12-year-old Brooklyn boy, Omar Rivera, died after a wound he received on the basketball court became infected with methicillin-resistant Staphylococcus aureus (MRSA), a bacterium that has become resistant to one of the most potent drug classes in the current antibiotic arsenal.
The prospect of healthy people contracting an untreatable bacterial infection may have seemed remote a decade ago, but it has now become a reality. In 2007 a research team led by Monina Klevens at the Centers for Disease Control and Prevention reported that MRSA causes 19,000 deaths every year in the U.S., which is more than HIV/AIDS causes. The number is especially alarming because almost 20 percent of people who contract MRSA die from it, and an increasing number of its victims are young, healthy people who were infected going about everyday activities. The problem was once limited to hospitals or nursing homes, where many people were already vulnerable because of impaired immunity. Even for those who survive, the price of MRSA is high: a patient who contracts it while hospitalized stays an average 10 days longer and costs an additional $30,000.
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18 Comments
Add CommentWould a cocktail of several antibiotics be better than either monotherapy or synergistic combinations? Theoretically assuming that the frequency of mutation to a particular antibiotic is 10 power x, for a cocktail of few more antibiotics the sum effect would be 10 power x + 10 power y + 10 power z, or 10 power xyz which is greater than the individual parts. I am just wondering if there is any clinical observation that prevents the use of such antibiotic cocktails.
Reply | Report Abuse | Link to thisWould a cocktail of several antibiotics be better than either monotherapy or synergistic combinations? Theoretically assuming that the frequency of mutation to a particular antibiotic is 10 power x, for a cocktail of few more antibiotics the sum effect would be 10 power x + 10 power y + 10 power z, or 10 power xyz which is greater than the individual parts. I am just wondering if there is any clinical observation that prevents the use of such antibiotic cocktails.
Reply | Report Abuse | Link to thisWould a cocktail of several antibiotics be better than either monotherapy or synergistic combinations? Theoretically assuming that the frequency of mutation to a particular antibiotic is 10 power x, for a cocktail of few more antibiotics the sum effect would be 10 power x + 10 power y + 10 power z, or 10 power xyz which is greater than the individual parts. I am just wondering if there is any clinical observation that prevents the use of such antibiotic cocktails.
Reply | Report Abuse | Link to thisWhile "superbugs" such as MRSA are indeed a problem, it is not the case that "almost 20% of people who contract MRSA die from it". MRSA is now the predominant strain of Staphylococcus aureus in many communities, and causes countless skin infections that are now routinely treated by most physicians as outpatients, with occasional more severe cases that require hospital admission, and even among these death is rare.
Reply | Report Abuse | Link to thisDavid Herbert, MD
Divisions of Infectious Diseases and Critical Care Medicine
Kaiser Permanente, Sacramento, CA
What about the use of phage treaments?
Reply | Report Abuse | Link to thishttp://newtechmd.com/wordpress/?p=39
Research Manuka HONEY! Known for centuries as a cure for many ailments - MRSA has a cure it seems - I don't have first-hand proof, but please check these links out.
Reply | Report Abuse | Link to thishttp://www.honeymarkproducts.com/anti-mrsa-kit.aspx
http://www.youtube.com/watch?v=m1U0JG9xvsY&feature=related
http://www.youtube.com/watch?v=HzXCgFnnvZs&feature=related
http://www.honeymarkproducts.com/relieving-pain-with-manuka-honey-and-other-natural-ingredients.aspx
Karthig,
Reply | Report Abuse | Link to thisI'm not quite sure on the effect of using such a "cocktail", but a significant problem with that is the fact that many of these strains of bacteria are not just resistant to a single type or even a single family of antibiotics. I've worked with E. Coli & E. Faecalis with plasmid(s) that coded for ribosomal protection proteins for several different antibiotics which include, but were not limited to: kanamycin, ampicillin, tetracycline, and vancomycin. The alarming part is that a single bacterium can have so many resistances. Furthermore, when incubated at human body temperature, their rate of binary fission increases to its maximum & the rate of conjugal transfers of F-plasmids (which encode for many resistances) through the pilus & simple plasmid transfers increase dramatically as well. Furthermore there can be a large number of different genes that code for a single type of resistance. Take, for example, tetracycline, there are nine different genes that code for RPP's for tetracycline alone. It's not simply a problem of curing the patients with what we currently have, but developing new antibiotics, or a new method of treatment (which is probably astronomically unlikely for the time being).
I think a great deal of the problem is caused by overuse of antibiotics. For the most part, the human body can deal with minor infections but we dose people with antibiotics anyway. On top of that, we only absorb a small portion of any medication we take while the rest is released in our waste. In fact, our water is so full of chemicals that fish are becomming sterile, switching genders (more often than they should, some do it naturally), causing increased percentages of certain genders of fish and creating new strains of antibiotic resistant bacteria. We're poisoning our water, and it seems to be poisoning us back, no matter how much we treat it.
Reply | Report Abuse | Link to thisThen you've also got the overuse of germicides around the home. We've got so many disinfectant wipes and sprays that our immune systems practically never get any "target practice" so that when we go out into the real world, we get hammered by stuff that we should be able to deal with naturally.
I'm not advocating that we stop using antibiotics. They are helping keep us alive and cure many ailments. However a few things need to be done:
1) They need to stop being over-prescribed.
2) We need to figure out a better delivery system for drugs that allows us to absorb as much as possible and release as little as possible as waste. Perhaps an antibiotic patch?
3) We need to move away from the overuse of household disinfectants.
There is such thing as better than antibiotics, its called probiotics. Everyone who educates themselves instead of blindly trusting your Doctor knows that. Antibiotics just inhibit your bodies immune system to fend off bacteria permanently. Doctors dont know how to heal, they are taught by the drug companies, they only treat symptoms. Which usually damages another part of the body. No wonder our health care system is in a crisis!
Reply | Report Abuse | Link to thisThe problem isn't always the overuse of antibiotics. Often, it's underuse. Consider the case of a patient who is carrying a disease mutation. At first, she will be carrying a combination of resistent and non-resistent bugs.
Reply | Report Abuse | Link to thisUsing a lot of antibiotics in a previously healthy patient isn't too bad because it will kill almost every bug that the doctor is trying to target in the patient's body, and the few that had resistance will be wiped out by the immune system. However, if the patient doesn't take the full prescribed course, the bugs that weren't resistant will not be wiped out. In conjunction with the resistent bugs, the disease will resurge. However the previous use of antibiotics would have flushed out some non-resistent bugs, so the proportion of resistent bugs will increase. Over time, with exposure to antibiotics, resistent bugs will thrive.
Someone found out that if you feed animals small amounts of antibiotics, they tend to grow larger than usual. This is great for the meat industry and almost all commercial meat animals are fed antibiotics regularly. However, they are rarely measured carefully enough to figure out what the proper dose is to kill any random disease the animal might be carrying. In essence, these meat animals are designed to be the perfect resistant-bug factories.
There is one piece of good news, though. There are some indications that if a class of antibiotics is taken out of circulation, resistance dies down.
Antibiotics are being used as a pallet of bricks to drop on various species of what we consider rodents. It's been an effective practice, to be sure, but one that I think needs to mature and refine as our medical expertise does as well.
Reply | Report Abuse | Link to thisI think the future of antibiotics isn't in finding new mass spectrum bacteria killers, but in getting specific drugs made to kill the specific bug in your system. Or perhaps a probiotic treatment (similar to phage therapy) that would rebalance the ecology of the human system.
There's a significant body of work about this kind of thing out there, not sure if it's been on SciAm before but here's what I have to share:
This is the most promising thing to being able to properly single out and kill problem bacteria - changing from the ton of bricks to a laser precise target:
http://www.ted.com/index.php/talks/bonnie_bassler_on_how_bacteria_communicate.html
Excellent article guys. One problem with "discovering" novel antibiotics from microbial sources (whether culturable or environmental) is that you often encounter naturally occurring resistance mechanisms clustered adjacent to the encoding genes in the producing host. In a sense, nature has already evolved a way to counter the drugs that we are still trying to turn on and discover. The rate at which we can turn on these biosynthetic pathways, characterize the metabolites, test them against resistant bacteria, go through rounds of clinical evaluation, and (the largest challenge considering microbial diversity) identify species-specific targets which may be unculturable themselves, will make this approach to discovery challenging. Rates of horizontal gene transfer of these resistance elements between unculturable species have also not been well studied in the context of a biome (I believe 3 species model systems have been studied at most, targeted HT sequencing technology should help begin to pull this story apart). Targeting general virulence mechanisms or metabolically manipulating pathogens to enhance susceptibility to existing treatments may help overcome the bacterial "persister" phenomenon. It seems as though bacterial rates of mutation and gene transfer will necessarily overcome many of our efforts to find new small molecule drugs. Bacteria are designed to do this and to sample favorable genetic elements even in the absence of specific chemical challenge (ala PNAS paper which sequenced stages of patient-derived VRSA).
Reply | Report Abuse | Link to thisAs per earlier comments, phage have evolved precise mechanisms to fight bacteria. Rational manipulation of these natural weapons may be a good approach. Concerted efforts to perform combinatorial biosynthesis for "unnatural" natural products can also help both generate novel pharmacophores with potentially novel targets (your earlier work) or can help us learn more about target ID of these molecules (J.Yin, Walsh) in the context of a biome.
I could go on for a while but this article was great and will hopefully help stimulate new ideas in the field.
In the article, emphasis has been given to the discovery of novel antibiotics from organisms yet unexplored for their secretions. It is understood that genes for existing antibiotics can be recognized in new organisms via homology studies. How does one then recognize genes for novel antibiotics in new organisms?
Reply | Report Abuse | Link to thisI have been troubled by the lack of culture and sensitivity testing by my college physicians. I recognize the barrier to better testing is faster lab results when cultures are obtained. Other barriers include excess paper work and phone calls to send results to patients and prescriptions to the pharmacy. Sensitivity testing allows appropriate antibiotic use. To help with the effort I have launched a web site to promote and facilitate culture use. The site (mommyimsick.com) allows submission of cultures and reporting of the results through a Hipaa compliant interface between MD, patient, lab, and pharmacy. No paper work, phone calls are needed. Once fully implemented can have a dramatic effect on infections, resistance and prevention of disease. The pooled culture results on a national (someday world-wide) data network should more rapidly predict outbreaks of diseases, many of which are not reportable to the CDC, but never the less cause significant morbidity to children and adults. Knowledge of active areas of infection including schools, daycare centers, malls, and travel systems should allow preventative measures to reduce the spread of infection. I invite comments on the project as we are moving out of beta test and into physician's offices this fall.
Reply | Report Abuse | Link to thisMark Widick MD
Otolaryngology
As a physician, I am often disturbed by the lack of rigor in the diagnosis of infections. The most definitive means is the use of bacterial culture with sensitivity testing. Barriers exist that limit the practicality of these tests. There are delays in the testing, and reporting of samples. Paper work intensive forms are required and phone calls to patients and pharmacies take up time that is often in short supply for a busy physician. This results in the over use of broad spectrum antibiotics, with ever increasing resistance to these drugs. (Often prescribned over the phone with no clinical evaluation at all) I have been working over the past 2 years with a clinical microbiologist (Brent Chester - Microbiology Associates of South Florida) to improve on the situation. We are in the final stages of a web site that can combine all the messages, paper work, prescriptions and notifications to patient into a few mouse clicks. Preliminary results are reported in less than 24 hours. The benefit of this is quicker response and greater acceptance by medical individuals. Secondary benefit will include a collection of data regarding the prevalence of non reportable diseases by location and time. Hot spots (ie daycare centers, schools, business, airlines, cruise ships etc.. can now be identified directly through a standard set of questions and demographic data collected from patients. This should help in reducing the spread of these infections through timely notices of areas of increased incidence. I invite comments. The site should you be so inclined is easy to remember www.MommyImSick.com. It is soon to be complete, is HIPAA compliant and incorporates ePrescribing software which allows MD a bonus payment from medicare, another reason that this should appeal and be adopted as a new standard in diagnosis and treatment of infectious diseases in the outpatient setting.
Reply | Report Abuse | Link to thisMark Widick MD
Otolaryngology
Boca Raton Florida
This article made me really angry at the myopia of the researchers. Bacteria don't respect the boundaries "Doctors of Human Medicine" assume they do. Most new infectious diseases come from animals we are in contact with. Most anti-biotics are not given to humans- since the 1980's they are given continuously to "healthy" farm animals in CAFO's (Concentrated Animal Feeding Operations).
Reply | Report Abuse | Link to thisIf you were a bioterrorist intent on making a superbug to kill a lot of people, you could not find a better laboratory than a modern factory pig or cow farm.
The current H1N1 virus seems to have emerged from a pig CAFO in Mexico. Hospital spread MRSA in Europe has been traced back to a hog farm in Denmark.
To not even mention the source of most new emerging diseases in this article was a sad ommision.
To learn more about the problem of emerging antibiotic resistance, see the Union of Concerned Scientists work to promote the "Preservation of Antibiotics for Medicine Act". http://ucsusa.org
http://www.ucsusa.org/food_and_agriculture/solutions/wise_antibiotics/pamta.html
Hi guys. Really good points.I'm currently working with the ReAct organisation in tandem with WHO regarding ABR. We're in the midst of creating a portal/forum for open discussion in the hope that the right policies can be implemented by WHO. If you know any blogs or other forums that are discussing this important issue please do let me know through lee23nickjohn@gmail.com
Reply | Report Abuse | Link to thisDo have a look at the ReAct website. Cheers guys.
Nicholas Lee
Hi guys. Really good points.I'm currently working with the ReAct organisation in tandem with WHO regarding ABR. We're in the midst of creating a portal/forum for open discussion in the hope that the right policies can be implemented by WHO. If you know any blogs or other forums that are discussing this important issue please do let me know through lee23nickjohn@gmail.com
Reply | Report Abuse | Link to thisDo have a look at the ReAct website. Cheers guys.
Nicholas Lee