From the 28 January 2015 press relase
WASHINGTON, Jan. 28, 2015 — Like the candy shell on an M&M ®, every cell on the planet has a carbohydrate coating that holds special information. But decoding these coatings has proven elusive. Now Laura Kiessling, Ph.D., and her team at University of Wisconsin-Madison are trying to unlock the mystery of these coatings, known as glycans. In the latest episode of Prized Science, Kiessling explains how glycans could hold the key to new antibiotics and other disease treatments. The video is available at http://youtu.be/D-9utC2fY0k.
From the 28 January 2015 University of Manchester press release
A way to eradicate cancer stem cells, using the side-effects of commonly used antibiotics, has been discovered by a University of Manchester researcher following a conversation with his young daughter.
Professor Michael P. Lisanti, Director of the Breakthrough Breast Cancer Unit, led the research. He was inspired to look at the effects of antibiotics on the mitochondria of cancer stem cells by a conversation with his daughter Camilla about his work at the University’s Institute of Cancer Sciences. Camilla is currently a student at the Moor Allerton Preparatory School.
His new paper, published in Oncotarget, opens up the possibility of a treatment for cancer, which is highly effective and repurposes drugs which have been safely used for decades.
Mitochondria are the ‘engine’ parts of the cells and are the source of energy for the stem cells as they mutate and divide to cause tumours. Cancer stem cells are strongly associated with the growth and recurrence of all cancers and are especially difficult to eradicate with normal treatment, which also leads to tumours developing resistance to other types of therapy.
Professor Lisanti said: “I was having a conversation with Camilla about how to cure cancer and she asked why don’t we just use antibiotics like we do for other illnesses. I knew that antibiotics can affect mitochondria and I’ve been doing a lot of work recently on how important they are to the growth of tumours, but this conversation helped me to make a direct link.”
Professor Lisanti worked with colleagues from The Albert Einstein College of Medicine, New York and the Kimmel Cancer Centre, Philadelphia. The team used five types of antibiotics – including one used to treat acne (doxycycline) – on cell lines of eight different types of tumour and found that four of them eradicated the cancer stem cells in every test. This included glioblastoma, the most aggressive of brain tumours, as well as lung, prostate, ovarian, breast, pancreatic and skin cancer.
Mitochondria are believed to be descended from bacteria which joined with cells early on in the evolution of life. This is why some of the antibiotics which are used to destroy bacteria also affect mitochondria, though not to an extent which is dangerous to people. When they are present in stem cells, mitochondria provide energy for growth and, crucially, for division, and it is this process going wrong which leads to cancer.
In the lab, the antibiotics had no harmful effect on normal cells, and since they are already approved for use in humans, trials of new treatments should be simpler than with new drugs – saving time and money.
Professor Lisanti said: “This research makes a strong case for opening new trials in humans for using antibiotics to fight cancer. Many of the drugs we used were extremely effective, there was little or no damage to normal cells and these antibiotics have been in use for decades and are already approved by the FDA for use in humans. However, of course, further studies are needed to validate their efficacy, especially in combination with more conventional therapies.”
Dr Matthew Lam, Senior Research Officer at Breakthrough Breast Cancer, said: “The conclusions that the researchers have drawn, whilst just hypotheses at this stage, are certainly interesting. Antibiotics are cheap and readily available and if in time the link between their use and the eradication of cancer stem cells can be proved, this work may be the first step towards a new avenue for cancer treatment.
“This is a perfect example of why it is so important to continue to invest in scientific research. Sometimes there are answers to some of the biggest questions right in front of us but without ongoing commitment to the search for these answers, we’d never find them.”
Importantly, previous clinical trials with antibiotics – intended to treat cancer-associated infections, but not cancer cells – have already shown positive therapeutic effects in cancer patients. These trials were performed on advanced or treatment-resistant patients.
In the lung cancer patients, azithromycin, the antibiotic used, increased one-year patient survival from 45% to 75%. Even lymphoma patients who were ‘bacteria-free’ benefited from a three-week course of doxycycline therapy, and showed complete remission of the disease. These results suggest that the antibiotic’s therapeutic effects were actually infection-independent.
“As these drugs are considerably cheaper than current therapies, they can improve treatment in the developing world where the number of deaths from cancer is predicted to increase significantly over the next ten years,” said Dr Federica Sotgia, another leader of the study.
The research was published in the journal Oncotarget and part-funded by Breakthrough Breast Cancer.
The paper is available here.
An article by Sayer Ji, Activist Post, provides some thought-provocation and a lateral approach to a science, vaccination, that is currently in the news for its controversial issues concerning adverse reactions.
A groundbreaking study published this month in Nature challenges a century-old assumption about the innate pathogenicity of these extremely small, self-replicating particles known as viruses.
Titled, “An enteric virus can replace the beneficial function of commensal bacteria,” researchers found that an “enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine.” Known as murine (mouse) noravirus (MNV), researchers found that infecting germ-free or antibiotic-treated mice infection with MNV “restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease.”
The researchers found:
Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria. Despite the commonly held belief that viruses are vectors of morbidity and mortality that must be vaccinated against in order to save us from inevitable harm and death, the new study dovetails with a growing body of research showing that our own genome is 80% viral in origin.
Find the full article here.
Date:November 12, 2014Source:ETH ZürichSummary:Medicine is drifting towards a major problem. An increasing number of bacteria is no longer sensitive to known antibiotics. Doctors urgently need to find new ways of fighting these multi-resistant pathogens. To address the problem, pharmaceutical research is turning back to the source of most of our drugs: nature.
Although hundreds of thousands of known active agents are found in nature, exactly how most of them work is unclear. A team of researchers from ETH Zurich has now developed a computer-based method to predict the mechanism of action of these natural substances. The scientists hope this method will help them to generate new ideas for drug development. “Natural active agents are usually very large molecules that often can be synthesized only through very laborious processes,” says Gisbert Schneider, a professor of computer-aided drug design at the Institute of Pharmaceutical Sciences at ETH Zurich. An understanding of the exact mechanism of action of a natural substance enables the design of smaller, less complex molecules that are easier to synthesize. Once a substance is chemically synthesized, it can be optimized for medical applications.
In order to understand the mechanism of action, researchers are studying which parts of a pathogen interact with the natural substance to inhibit its growth for example. In the past, this involved highly complex laboratory tests through which scientists usually identified only the strongest effect of a substance. However, this interaction alone is often unable to explain the entire effect of a natural substance. “Minor interactions with other target structures can contribute to the overall effect as well,” explains Schneider.
“By using the computer to break down the molecules, which can be quite large, into separate building blocks, we discover which parts might be essential for the mechanism of action,” says Schneider. Thus, it might be possible to design less complex molecules that chemists could synthesize instead of the laborious process of isolating them from the natural source.
Analysis of 210,000 natural substances
Using the computer-based method, the researchers led by Gisbert Schneider were able to predict a variety of potential target structures for 210,000 known natural substances.
Designer viruses could be the new antibiotics | Ars Technica.by Oct 16 2014, 11:30am EDT
From the news article
Bacterial infections remain a major threat to human and animal health. Worse still, the catalog of useful antibiotics is shrinking as pathogens build up resistance to these drugs. There are few promising new drugs in the pipeline, but they may not prove to be enough. Multi-resistant organisms—also called “superbugs”—are on the rise, and many predict a gloomy future if nothing is done to fight back.
The answer, some believe, may lie in using engineered bacteriophages, a type of virus that infects bacteria. Two recent studies, both published in the journal Nature Biotechnology, show a promising alternative to small-molecule drugs that are the mainstay of antibacterial treatments today.
From basic to synthetic biology
Nearly every living organism seems to have evolved simple mechanisms to protect itself from harmful pathogens. These innate immune systems can be a passive barrier, blocking anything above a certain size, or an active response that recognizes and destroys foreign molecules such as proteins and DNA.
An important component of the bacterial immune system is composed of a family of proteins that are tasked specifically with breaking down foreign DNA. Each bug produces a set of these proteins that chew the genetic material of viruses and other micro-organism into pieces while leaving the bacterial genome intact.
In vertebrates, a more advanced system—called the adaptive immune system—creates a molecular memory of previous attacks and prepares the organism for the next wave of infection. This is the principle on which vaccines are built. Upon introduction of harmless pathogen fragments, the adaptive immunity will train specialist killer cells that later allow a faster and more specific response if the virulent agent is encountered again.
Until recently, people thought bacteria were too simple to possess any sort of adaptive immunity. But in 2007, a group of scientists from the dairy industry showed that bacteria commonly used for the production of cheese and yogurts could be “vaccinated” by exposure to a virus. Two years earlier, others noticed similarities between repetitive sections in bacterial genomes and the DNA of viruses. These repetitive sequences—called CRISPR for “clustered regularly interspaced short palindromic repeats”—had been known for 20 years, but no one could ever explain their function.
From the October 2014 press release
SAN DIEGO – When parents take a sick or injured child to the doctor or emergency room, they often expect tests to be done and treatments given. So if the physician sends them on their way with the reassurance that their child will get better in a few days, they might ask: “Shouldn’t you do a CT scan?” or “Can you prescribe an antibiotic?”
What families — and even doctors — may not understand is that many medical interventions done “just to be safe” not only are unnecessary and costly but they also can harm patients, said Alan R. Schroeder, MD, FAAP, who will present a plenary session at the American Academy of Pediatrics (AAP) National Conference & Exhibition. Titled “Safely Doing Less: A Solution to the Epidemic of Overuse in Healthcare,” the session will be held from 11:30-11:50 a.m. PDT Monday, Oct. 13 in Ballroom 20 of the San Diego Convention Center.
Dr. Schroeder, chief of pediatric inpatient services and medical director of the pediatric intensive care unit at Santa Clara Valley Medical Center in San Jose, Calif., will discuss some of the reasons why doctors provide unnecessary care (i.e., barriers to safely doing less), including pressure from parents and a fear of missing something.
“We all have cases where we’re haunted by something bad happening to a patient. Those tend to be cases where we missed something,” he said. “We tend to react by doing more and overtreating similar patients.”
He also will give examples of where overuse commonly occurs in pediatrics, such as performing a CT scan on a child with a minor head injury, and the negative consequences.
“You may find a tiny bleed or a tiny skull fracture, and once you’ve found that you’re compelled to act on it. And generally acting on it means at a minimum admitting the child to an intensive care unit for observation even if the child looks perfectly fine,” Dr. Schroeder said. “The term for that is overdiagnosis. You detect an abnormality that will never cause harm.”
Finally, he will suggest ways to minimize overtesting and overtreatment, highlighting the Choosing Wisely campaign. More than 60 medical societies including the AAP have joined the initiative and have identified more than 250 tests and procedures that are considered overused or inappropriate in their fields.
“I’ve devoted much of my research to identify areas in inpatient pediatrics where we can safely do less — which therapies that we are doing now are unnecessary or overkill,” Dr. Schroeder said.
The American Academy of Pediatrics is an organization of 62,000 primary care pediatricians, pediatric medical subspecialists and pediatric surgical specialists dedicated to the health, safety and well-being of infants, children, adolescents and young adults. For more information, visit http://www.aap.org.
New types of drug intended for use in place of antibiotics have been given a cautious welcome by scientists.
University researchers have been probing the long-term effectiveness of drugs currently being developed by the pharmaceutical industry.
These work by limiting the symptoms caused by a bug or virus in the body, rather than killing it outright.
These treatments are designed to avoid the problem of infections becoming resistant to treatment, which has become widespread with antibiotics.
This approach is intended to enable the patient to tolerate disease, and buy the immune system valuable time to get rid of the infection naturally.
Researchers at the Universities of Edinburgh and Liverpool created a mathematical model to look at how at how drugs that limit the damage caused by disease could affect how infections spread and evolve.
They found that for certain infections, where the symptoms are not linked to the spread of disease, these drugs may prevent disease from evolving too quickly.
They will be useful over longer periods of time.
However, scientists caution that people given damage limitation treatments may appear healthy, but carry high levels of infection and so may be more likely to pass on disease.
In addition, people with lesser symptoms could remain undiagnosed and add to the spread of disease.
In treating infections with drugs, we change their environment, but bacteria and other infectious agents are incredibly good at adapting to their environment. Damage limitation therapies may be a useful alternative to antibiotics, but we should be cautious, and investigate their potential long-term consequences. Limiting damage may work for the individual, but could, in some cases, increase disease spread.
Dr Pedro Vale
School of Biological Sciences
Researchers at Oregon State University and other institutions today announced the successful use of a new type of antibacterial agent called a PPMO, which appears to function as well or better than an antibiotic, but may be more precise and also solve problems with antibiotic resistance.
- Beyond antibiotics: “PPMOs” offer new approach to bacterial infection (konterkariert.tumblr.com)
- Beyond antibiotics: ‘PPMOs’ offer new approach to bacterial infection, other diseases (eurekalert.org)
- UT Southwestern reports promising new approach to drug-resistant infections (eurekalert.org)
- AAP Updates Antibiotic Use for Sinusitis (wordofmomtoddler.wordpress.com)
- New Studies Show Drop in C.diff and VRE Infection Rates When Xenex UV Room Disinfection Utilized as Alternative to Bleach (hispanicbusiness.com)
- Stay Strapped: Anti-Bacterial Resistant Gonorrhea Among Dangerous Diseases Becoming Impossible To Cure (bossip.com)
Could pave way for development of enhanced delivery and storage in third world, save billions in cost
Researchers funded by the National Institutes of Health have developed a new silk-based stabilizer that, in the laboratory, kept some vaccines and antibiotics stable up to temperatures of 140 degrees Fahrenheit. This provides a new avenue toward eliminating the need to keep some vaccines and antibiotics refrigerated, which could save billions of dollars every year and increase accessibility to third world populations.
Vaccines and antibiotics often need to be refrigerated to prevent alteration of their chemical structures; such alteration can result in less potent or ineffective medications. By immobilizing their bioactive molecules using silk protein matrices, researchers were able to protect and stabilize both live vaccines and antibiotics when stored at higher than recommended temperatures for periods far longer than recommended….
- Vaccine and antibiotics stabilized so refrigeration is not needed – NIH study (nih.gov)
- New silk technology stabilizes vaccine and antibiotics so refrigeration is not needed (medicalxpress.com)
- Vaccine and antibiotics stabilized so refrigeration is not needed — NIH study (eurekalert.org)
- Stabilizer cuts need to refrigerate drugs (upi.com)
- Stabilization of vaccines and antibiotics in silk (nextbigfuture.com)
- Why Silk May Be Added To Vaccines Someday (wnyc.org)
- Silky scheme for vaccine storage without refrigeration (newscientist.com)
- Silky scheme for vaccine storage without refrigeration (newscientist.com)
- New silk technology preserves heat-sensitive drugs for months without refrigeration (biologynews.net)
- Silk Preserves Heat-Sensitive Drugs for Months without Refrigeration (blogs.voanews.com)
From the KevinMD article of Mon Jan 30, 2012
Whenever someone is scheduled for an operation, the assigned nurse is required to fill out a “pre-op checklist” to ensure that all safety and quality metrics are being adhered to. Before the patient is allowed to be wheeled into the OR we make sure the surgical site is marked, the consents are signed, all necessary equipment is available, etc. One of the most important metrics involves the peri-operative administration of IV antibiotics. SCIP guidelines mandate that the prophylactic antibiotic is given within an hour of incision time to optimize outcomes. This has been drilled into the heads of physicians, health care providers, and ancillary staff to such an extent that it occasionally causes total brain shutdown.
Let me explain. For most elective surgeries I give a single dose of antibiotics just before I cut. For elective colon surgery, the antibiotics are continued for 24 hours post-op. This is accepted standard of care. You don’t want to give antibiotics inappropriately or continue them indefinitely.
But what about a patient with gangrenous cholecystitis or acute appendicitis? What if, in my clinical judgment, I want to start the patient on antibiotics right away (i.e. several hours before anticipated incision time) and then continue them for greater than 24 hours post-op, depending on what the clinical status warrants? I should be able to do that right?
Well, you’d be surprised. You see, at two different, unaffiliated hospitals I cover, the surgeons have seen that decision-making capability removed from their power….
Some of the nastiest smelling creatures on Earth have skin that produces the greatest known variety of antibacterial substances that hold promise for becoming new weapons in the battle against antibiotic-resistant infections, scientists are reporting. Their research is on amphibians so smelly (like rotten fish, for instance) that scientists term them “odorous frogs.”..
Antibiotic overuse and resistance have emerged as major threats during the past two decades. Following an outbreak of Clostridium difficile infections, which often result from antibiotic use, health care professionals in Quebec, Canada targeted physicians and pharmacists with an education campaign that reduced outpatient antibiotic use, according to a study published in Clinical Infectious Diseases and now available online.
The Quebec Minister of Health and the Quebec Medication Council collaborated with designated physicians and pharmacists to develop guidelines to improve prescribing practices. First issued in January 2005, the guidelines emphasized proper antibiotic use, including not prescribing antibiotics when viral infections were suspected and selecting the shortest possible duration of treatment. Approximately 30,000 printed copies of the original recommendations were distributed to all physicians and pharmacists in Quebec. An additional 193,500 copies were downloaded from the Medication Council’s website.
(The current versions of the guidelines are available online: http://www.cdm.gouv.qc.ca/site/aid=166.phtml.)
During the year after the guidelines were initially distributed, the number of outpatient antibiotic prescriptions in Quebec decreased 4.2 percent. In other Canadian provinces, the number of these prescriptions increased 6.5 percent during the same period.
According to study author Karl Weiss, MD, of the University of Montreal, “It is possible to decrease antibiotic consumption when physicians, pharmacists, state governments, etc., are working together for a common goal. This is the key to success: having everybody involved and speaking with a common voice.”
Dr. Weiss added, “Simple, short, easy-to-use guidelines have an impact on physicians when they are readily available. The web is an increasingly important tool to reach our audience and should now be used as such in the future. With handheld electronic devices available for all health care professionals, these downloadable guidelines can be accessed and used at any time and any circumstance.”
- Superbug gonorrhoea found in Japan (newscientist.com)
- Drug-resistant STD prompts global warning (independent.co.uk)
- (Reuters) – Scientists have found a “superbug” strain of gonorrhea in Japan that is resistant to all recommended antibiotics and say it could transform a once easily treatable infection into a global public health threat. (theboldcorsicanflame.wordpress.com)
A drugstore within –Mesenchymal stem cells protect and heal
A stem cell that can morph into a number of different tissues is proving a natural protector, healer and antibiotic maker, researchers at Case Western Reserve University and their peers have found.
Mesenchymal stem cells reaped from bone marrow had been hailed as the key to growing new organs to replace those damaged or destroyed by violence or disease, but have failed to live up to the billing.
Instead, scientists who’d been trying to manipulate the cells to build replacement parts have been finding the cells are innately potent antidotes to a growing list of maladies.
The findings are summarized in the July 8 issue of Cell Stem Cell.
The cell, referred to as an MSC, “is a drugstore that functions at the local site of injury to provide all the medicine that site requires for its successful regeneration,” said Arnold Caplan, professor of biology at Case Western Reserve, and lead author of the paper.
Here’s how: (click here for rest of article)
ScienceDaily (Mar. 20, 2011) — A team of scientists from the University of Oxford, U.K. have taken lessons from Adam Smith and Charles Darwin to devise a new strategy that could one day slow, possibly even prevent, the spread of drug-resistant bacteria. In a new research report published in the March 2011 issue of Genetics, [Abstract***]the scientists show that bacterial gene mutations that lead to drug resistance come at a biological cost not borne by nonresistant strains. They speculate that by altering the bacterial environment in such a way to make these costs too great to bear, drug-resistant strains would eventually be unable to compete with their nonresistant neighbors and die off.“Bacteria have evolved resistance to every major class of antibiotics, and new antibiotics are being developed very slowly; prolonging the effectiveness of existing drugs is therefore crucial for our ability to treat infections,” said Alex Hall, Ph.D., a researcher involved in the work from the Department of Zoology at the University of Oxford. “Our study shows that concepts and tools from evolutionary biology and genetics can give us a boost in this area by identifying novel ways to control the spread of resistance.”
The research team measured the growth rates of resistant and susceptible Pseudomonas aeruginosa bacteria in a wide range of laboratory conditions. They found that the cost of antibiotic resistance has a cost to bacteria, and can be eliminated by adding chemical inhibitors of the enzyme responsible for resistance to the drug. Leveling the playing field increased the ability of resistant bacteria to compete effectively against sensitive strains in the absence of antibiotics. Given that the cost of drug resistance plays an important role in preventing the spread of resistant bacteria, manipulating the cost of resistance may make it possible to prevent resistant bacteria from persisting after the conclusion of antibiotic treatment. For instance, new additives or treatments could render antibiotic resistance more costly for bacteria, making it less likely that the resistant strains will persist at the end of treatment.
“If we’ve learned one thing about microscopic organisms over the past century, it’s that they evolve quickly, and that we can’t stop the process,” said Mark Johnston, Editor-in-Chief of the journal GENETICS. “This research turns this fact against the bacteria. This is an entirely new strategy for extending the useful life of antibiotics, and possibly for improving the potency of old ones.”
- Antibiotic resistance is not just genetic (sciencedaily.com)
- Pollution with antibiotics leads to resistant bacteria (physorg.com)
- Hospital infections: Unique antibody from llamas provide weapon against Clostridium difficile (ScienceDaily [news article])
Careful cleaning of children’s skin wounds key to healing, regardless of antibiotic choice
Hopkins Children’s study suggests antibiotics may not always be best therapy
When it comes to curing skin infected with the antibiotic-resistant bacterium MRSA (methicillin-resistant Staphylococcus aureus), timely and proper wound cleaning and draining may be more important than the choice of antibiotic, according to a new Johns Hopkins Children’s Center study. The work is published in the March issue of Pediatrics.
Researchers originally set out to compare the efficacy of two antibiotics commonly used to treat staph skin infections, randomly giving 191 children either cephalexin, a classic anti-staph antibiotic known to work against the most common strains of the bacterium but not MRSA, or clindamycin, known to work better against the resistant strains. Much to the researchers’ surprise, they said, drug choice didn’t matter: 95 percent of the children in the study recovered completely within a week, regardless of which antibiotic they got.
The finding led the research team to conclude that proper wound care, not antibiotics, may have been the key to healing.
“The good news is that no matter which antibiotic we gave, nearly all skin infections cleared up fully within a week,” says study lead investigator Aaron Chen, M.D., an emergency physician at Hopkins Children’s. “The better news might be that good low-tech wound care, cleaning, draining and keeping the infected area clean, is what truly makes the difference between rapid healing and persistent infection.”
Chen says that proper wound care has always been the cornerstone of skin infection treatment but, the researchers say, in recent years more physicians have started prescribing antibiotics preemptively.
Although the Johns Hopkins investigators stop short of advocating against prescribing antibiotics for uncomplicated MRSA skin infections, they call for studies that directly measure the benefit — if any — of drug therapy versus proper wound care. The best study, they say, would compare patients receiving placebo with those on antibiotics, along with proper wound cleaning, draining and dressing.
Antibiotics can have serious side effects, fuel drug resistance and raise the cost of care significantly, the researchers say.
“Many physicians understandably assume that antibiotics are always necessary for bacterial infections, but there is evidence to suggest this may not be the case,” says senior investigator George Siberry, M.D., M.P.H., a Hopkins Children’s pediatrician and medical officer at the Eunice Kennedy Shriver Institute of Child Health & Human Development. “We need studies that precisely measure the benefit of antibiotics to help us determine which cases warrant them and which ones would fare well without them.”
The 191 children in the study, ages 6 months to 18 years, were treated for skin infections at Hopkins Children’s from 2006 to 2009. Of these, 133 were infected with community-acquired MRSA, and the remainder had simple staph infections with non-resistant strains of the bacterium. Community-acquired (CA-MRSA) is a virulent subset of the bacterium that’s not susceptible to most commonly used antibiotics. Most CA-MRSA causes skin and soft-tissue infections, but in those who are sick or have weakened immune systems, it can lead to invasive, sometimes fatal, infections.
At 48-hour to 72-hour follow-ups, children treated with both antibiotics showed similar rates of improvement — 94 percent in the cephalexin group improved and 97 percent in the clindamycin group improved. By one week, the infections were gone in 97 percent of patients receiving cephalexin and in 94 percent of those on clindamycin. Those younger than 1 year of age and those whose infections were accompanied by fever were more prone to complications and more likely to be hospitalized.
Co-authors on the study included Karen Carroll, M.D., Marie Diener-West, Ph.D., Tracy Ross, M.S., Joyce Ordun, M.S., C.R.N.P., Mitchell Goldstein, M.D., Gaurav Kulkarni, M.D., and J.B. Cantey, M.D., all of Hopkins.
The research was funded by a grant from the Thrasher Research Foundation and the General Clinical Research Center at Johns Hopkins.
Knowledge Gaps, Fears Common Among Parents of Children with Drug-Resistant Bacteria http://www.hopkinschildrens.org/Fears-Common-Among-Parents-of-Children-with-Drug-Resistant-Bacteria.aspx
Community-Acquired MRSA Becoming More Common in Pediatric ICU Patients http://www.hopkinschildrens.org/Community-Acquired-MRSA-Becoming-More-Common-in-Pediatric-ICU-Patients.aspx
COLLEGE STATION, Texas, Dec. 23, 2010—Studying how bacteria incorporate foreign DNA from invading viruses into their own regulatory processes, Thomas Wood, professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, is uncovering the secrets of one of nature’s most primitive immune systems.
His findings, which appear in “Nature Communications,” a multidisciplinary publication dedicated to research in all areas of the biological, physical and chemical sciences, shed light on how bacteria have throughout the course of millions of years developed resistance to antibiotics by co-opting the DNA of their natural enemies—viruses.
The battle between bacteria and bacteria-eating viruses, Wood explains, has been going on for millions of years, with viruses attempting to replicate themselves by – in one approach – invading bacteria cells and integrating themselves into the chromosomes of the bacteria. When this happens a bacterium makes a copy of its chromosome, which includes the virus particle. The virus then can choose at a later time to replicate itself, killing the bacterium—similar to a ticking time bomb, Wood says.
However, things can go radically wrong for the virus because of random but abundant mutations that occur within the chromosome of the bacterium. Having already integrated itself into the bacterium’s chromosome, the virus is subject to mutation as well, and some of these mutations, Wood explains, render the virus unable to replicate and kill the bacterium.
With this new diverse blend of genetic material, Wood says, a bacterium not only overcomes the virus’ lethal intentions but also flourishes at a greater rate than similar bacteria that have not incorporated viral DNA.
“Over millions of years, this virus becomes a normal part of the bacterium,” Wood says. “It brings in new tricks, new genes, new proteins, new enzymes, new things that it can do. The bacterium learns how to do things from this.
“What we have found is that with this new viral DNA that has been trapped over millions of years in the chromosome, the cell has created a new immune system,” Wood notes. “It has developed new proteins that have enabled it to resists antibiotics and other harmful things that attempt to oxidize cells, such as hydrogen peroxide. These cells that have the new viral set of tricks don’t die or don’t die as rapidly.”
Understanding the significance of viral DNA to bacteria required Wood’s research team to delete all of the viral DNA on the chromosome of a bacterium, in this case bacteria from a strain of E. coli. Wood’s team, led by postdoctoral researcher Xiaoxue Wang, used what in a sense could be described as “enzymatic scissors” to “cut out” the nine viral patches, which amounted to precisely removing 166,000 nucleotides. Once the viral patches were successfully removed, the team examined how the bacterium cell changed. What they found was a dramatically increased sensitivity to antibiotics by the bacterium.
While Wood studied this effect in E. coli bacteria, he says similar processes have taken place on a massive, widespread scale, noting that viral DNA can be found in nearly all bacteria, with some strains possessing as much as 20 percent viral DNA within their chromosome.
“To put this into perspective, for some bacteria, one-fifth of their chromosome came from their enemy, and until our study, people had largely neglected to study that 20 percent of the chromosome,” Wood says. “This viral DNA had been believed to be silent and unimportant, not having much impact on the cell.
“Our study is the first to show that we need to look at all bacteria and look at their old viral particles to see how they are affecting the bacteria’s current ability to withstand things like antibiotics. If we can figure out how the cells are more resistant to antibiotics because of this additional DNA, we can perhaps make new, effective antibiotics.”
The US Centers for Disease Control publishes a wealth of information about antibiotics for consumers, health practitioners, and the media.
Topics include appropriate antibiotic use, dangers of antibiotic resistance, and an antibiotic quiz.
Information for Everyone includes both print and online materials, fact sheets, and Q and A’s.
Information for Healthcare Providers includes Treatment Guidelines, Patient Education Materials, and Continuing Education materials.
Presentations also track antibiotic prescriptions, new drugs
FRIDAY, Oct. 22 (HealthDay News) — An increasingly stubborn strain of methicillin-resistant Staphylococcus aureus, or MRSA, a common bacterial infection acquired in hospitals, has been identified in Ohio, according to research presented at the  annual meeting of the Infectious Diseases Society of America.
The strain, ST239 MRSA, killed 22 percent of the people it infected within 30 days, the study found. It’s the first time that the strain, originally identified in Brazil, has been seen in the United States since the 1990s.
“It does have epidemic potential for outbreak,” the study’s co-author, Dr. Shu-Hua Wang, said. “It has increased capacity to cause invasive, serious infection.”
Wang’s group reported that 6.8 percent — or 77 — of 1,126 MRSA samples collected through the Ohio State University Health Network and seven rural hospitals in a three-year period from January 2007 to January 2010 were ST239.
Wang, who is an assistant professor of medicine at Ohio State, called for more genotyping of MRSA isolates.
A second study presented at the conference found that antibiotic prescriptions in the United States were much higher in the South than in the West, a finding that held for all types of antibiotics……
Among other research being presented at the conference, which concludes Sunday in Vancouver, Canada: three new drugs appear to show promise in fighting MRSA and other bacteria when current antibiotics fail.
- Fusidic acid, which could fight S. aureus. “This is pretty exciting because it has no cross-resistance with any class of antibiotics so it could be used widely,” said Dr. Ronald N. Jones, chief executive of JMI Laboratories in North Liberty, Iowa, which makes the drug and funded the study being presented.
- JNJ-Q2. This potential agent belongs to a class of drugs known as fluoroquinolones and may be effective against S. aureus, including the methicillin-resistant form. “JNJ-Q2 was 16 times more potent than the existing marketed fluoroquinolones,” Jones said. The drug is moving into phase 2 and phase 3 trials, he said.
- A version of cephalosporin. It “may enable us to treat a broader spectrum of drug-resistant bacteria, although it probably won’t be on the market till 2013 or 2014,” Jones said.
Also being presented at the conference is a study involving a computer model that found that “universal contact precautions” — requiring anyone visiting a MRSA patient in the hospital to wear gloves and a gown — were more effective at preventing MRSA infection among patients in intensive-care units than were other strategies.
But the approach was expensive. The study’s lead author, Dr. Courtney A. Gidengil, an instructor in pediatrics at Children’s Hospital of Boston and Harvard Medical School, said that other strategies might be less effective but they are also less costly.
Another study presented at the conference found that carbapenem-resistant Enterobacteriaceae, or CRE, which carries a high mortality rate, is becoming more prevalent in the Chicago area.
Editor Flahiff’s note: If you need assistance tracking down studies in this news item, contact a reference librarian at your local public, academic, or medical library. Alternatively, you may contact me at firstname.lastname@example.org. I will reply within 48 hours. At the very least, I will provide contact information for a study’s author(s). Many study author’s are happy to share at least citations to their works, if not full text of their studies.
AHRQ Researchers Study How Community-Acquired Methicillin-Resistant Staphylococcus aureus Is Managed in Health Care Settings
Findings from three new AHRQ-funded reports on community-acquired methicillin-resistant Staphylococcus aureus (MRSA) are now available. The reports result from two-year projects conducted by AHRQ’s Practice-Based Research Networks in Colorado, Iowa, and North Carolina. Select below to access each report.
- Management by Primary Care Clinicians of Patients Suspected of Having Community-Acquired Methicillin-Resistant Staphylococcus AureusInfections—State Network of Colorado Ambulatory Practices and Partners. Researchers tested interventions for two health networks to optimize treatment for skin and soft tissue infections consistent with the community-acquired MRSA guidelines developed by the Centers for Disease Control and Prevention. They found the intervention resulted in an increase in antibiotic use and the proportion of prescribed antibiotics that covered MRSA.
- Community-Acquired Skin Infections in the Age of Methicillin-Resistant Organisms—Iowa Research Network Practices, University of Iowa. Researchers assessed how family physicians in rural areas managed patients with skin and soft tissue infections after introducing Centers for Disease Control and Prevention guidelines. They used chart review and/or follow-up to compare infection management and antibiotic therapy in patients before and after the CDC guidelines were introduced. They found that providers were more likely to prescribe antibiotics that covered MRSA at the initial patient visit after the guidelines were implemented.
- Cellulitis and Abscess Management in the Era of Resistance to Antibiotics (CAMERA)—Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill & Duke Clinical Research Institute. Researchers worked with nine primary care practices to improve the quality of care for individuals with skin or soft tissue infections. As a result, they developed recommendations and strategies for diagnosing and managing community-acquired MRSA in these settings. For example, researchers recommend that practices develop documentation and coding presentations; integrate templates into electronic medical records for describing skin and soft tissue infections; and hold workshops in the management of skin and soft tissue infections.
The continued use of antimicrobial drugs to promote growth in chickens, cattle and other livestock is tied to antibiotic resistance and should be phased out for that purpose, the U.S. Food and Drug Administration said Monday.
News item may be found here.