By Anne-Marie Walsh
Saturday June 09 2007
Irish hospitals come seventh in a league table of incidents of the deadly infection across 29 countries, according to new EU figures.
The research confirms that patients are highly exposed to the hospital-based bacteria and the rate of infection has not improved since 2001.
Only six other countries, Romania, Cyprus, Malta, Portugal, the UK and Greece (in that order), have a higher rate of the antibiotic-resistant infection.
However, a spokesperson for the ECDC pointed out that the Irish figures could be misleading.
"One of the reasons that Ireland and the UK have relatively high levels of MRSA is that they are quite active in monitoring it," he said.
"Some other EU countries may not be looking as hard or monitoring it as well."
But he added: "Compared with Ireland, the Netherlands and Scandinavia have been quite successful in preventing MRSA.
The level of MRSA in Ireland has risen in the last 10 years and has levelled off."
The investigation by the EU Centre for Disease Prevention and Control (ECDC) shows that the rate of MRSA went up by 1pc in the latest available year's data.
It is at the same level it was at in 2001, and 3pc higher than the 1999 rate of 39pc, suggesting that Government initiativeson eradication have had little impact.
The ECDC warned last night that the spread of hospital-acquired infections was now the main disease threat in Europe.
It said that, if the present "rapid negative development" was not halted, mankind would soon lose one of its most important weapons against infectious disease - antibiotics.
MRSA (methicillin-resistant staphylococcus aureus) is one of the bugs in the staphylococcus aureus family of bacteria that cannot be treated with drugs.
It made up 42pc of the 1,360 detected infections in this family of bacteria in Ireland in 2005.
This represented 571 people, according to the authors of the pioneering report from the ECDC.
The rest of the cases infected with the staphylococcus aureus bacteria could be treated with drugs.
MRSA is among the forms of superbugs from the staphylococcus aureus family of bacteria that are resistant to antibiotics.
They can live on the skin and in the nose and cause a variety of illnesses including meningitis and septicaemia.
If the bacteria enters the bloodstream, it can be extremely dangerous and is potentially fatal if it belongs to the variety that is resistant to antibiotics.
The ECDC report on infectious diseases ranked countries based on the proportion of S-aureus infections found to be antibiotic-resistant.
Romania topped the table with the highest proportion of the superbug, at over 60pc.
Every year, around 3m people in the EU catch a healthcare-associated infection, of whom around 50,000 die.
One in every 10 patients admitted to hospital in the EU will catch an infection there.
"One of the biggest challenges we face is the emergence of new microbes against which our defences are weak, or even non-existent," said Markos Kyprianou, European Commissioner for Health.
"Pandemic preparedness is, and must remain, a priority for the EU."
- Anne-Marie Walsh
Tuesday, June 12, 2007
Saturday, June 9, 2007
Biofilms -- slimy layers of bacteria that antibiotics don't fully kill -- are found in hospitals, kitchens, even your mouth. Scientists are on the att
WHETHER on a contact lens or a catheter, in your lungs or in your ears, a few bacterial invaders can set up a slimy fortress that can prove almost impossible to demolish. All it takes is a wet surface and a few days.
The sticky mess is called a biofilm, a slick layer of bacteria that is one of the biggest problems facing medicine today. Biofilms are forcing scientists to reevaluate their view of bacteria as free-floating bugs to one of sophisticated communities stuck on surfaces.
The National Institutes of Health estimates that more than 80% of microbial infections in the human body are caused by biofilms, many of them creating chronic and reoccurring problems. Two of the most serious: The layer of Pseudomonas aeruginosa that forms in the trachea of cystic fibrosis patients and the hospital-acquired infections resulting from biofilm formation on implanted medical devices.
Even the healthiest among us deals with biofilms on a daily basis in the form of dental plaque. And biofilms containing a pathogenic strain of E. coli were behind the spinach recall in October.
The problem with biofilms is that, because of their tightknit structure, they are resistant to traditional disinfectants and antibiotics. New research is aimed at finding ways to battle these goo-covered conglomerates. By understanding how biofilms thrive, scientists are devising new strategies for defeating them.
Biofilms form in a series of steps that scientists are just starting to understand. Step one occurs when a few bacteria attach to a surface. They activate certain genes within their genomes and inactivate others, starting their transformation from free-floaters to biofilm.
The bacteria begin to secrete polymers that hold aggregates of cells together. Then, as the biofilm grows, it becomes more complex and even starts to act like a multicellular organism.
Structures arise — such as channels to bring in nutrients and take away wastes.
Bacteria in different areas of the biofilm take on different roles. Some cells secrete enzymes, while others continue to make sticky matrix proteins. Some bacteria continue to rapidly divide, while others enter a dormant state.
The heterogeneity of biofilms is part of what makes them so robust, says Phil Stewart, director of the Center for Biofilm Engineering at Montana State University in Bozeman. A drug that can kill some of the bacteria in the biofilm might be useless against some of their neighbors.
The final step in the biofilm life cycle is dispersion. As conditions get crowded and resources become scarce, groups of cells detach and float away — potentially setting up new biofilms if they happen to land in a good spot.
"It's a little bit like seeds," Stewart says.
In many chronic and recurring infections — such as ear infections, prostatitis in men, urinary tract infections and endocarditis — these biofilm seeds set off the immune system and cause symptoms such as fever and inflammation that signal to doctor and patient that something's amiss.
When antibiotics are administered, the free-floating bacteria are killed. But the original biofilm remains unscathed. Although the infection appears to be cured, it is only a matter of time before another chunk of biofilm is set free and the symptoms return.
There are no good ways to fight biofilms because an awareness of their importance has only emerged in the last decade, Stewart says. Before that, research on bacteria focused on homogeneous cultures of fast-growing cells in flasks. Tools that fight these kinds of bacteria are great for acute infections in which bacteria are freely floating in the body. But they are almost useless against biofilms.
The Center for Biofilm Engineering is trying to change this by developing standardized methods for working with biofilms that the whole research community can use. A few companies and academic scientists are already exploring new avenues in treating and preventing biofilms.
One of the problems with today's antibiotics is that many only attack bacteria that are actively growing. This means that the dormant cells in a biofilm will escape treatment and be left behind to regrow the biofilm. So one approach to fighting biofilms is to come up with drugs that can kill all the biofilm residents.
Cubist Pharmaceuticals in Lexington, Mass., developed an antibiotic called daptomycin (marketed as Cubicin) that is able to do just that, enabling doctors to eradicate a biofilm with drug treatment.
But even if you could use antibiotics to kill all the bacteria in a biofilm, that might not be the best idea, says Wenyuan Shi, professor of oral biology and medicine at UCLA's School of Dentistry.
"Think of a lawn infested with dandelions," he says. "If you kill everything, the dandelions will come back first. But if you use a dandelion-specific killer and the grass fills in the lawn, the dandelions won't come back."
Many biofilms are composed of both good and bad bacteria. Shi's lab has developed a "smart bomb" that targets the harmful bacteria in a biofilm. A short antimicrobial peptide is attached to another one that mimics a pheromone used by bacteria to communicate. This hybrid bacteria-fighting molecule attaches to certain bacteria and makes sure only the targeted bugs are killed.
Shi has formed a Los Angeles-based company, C3Jian, to develop this technique for use in dental hygiene products. The company recently received the go-ahead for a clinical pilot study of a dental varnish that incorporates its peptides. It expects to have a product on the market in about three years.
Another approach to fighting biofilms is to try to break up their slimy coating and return them to the free-floating state that scientists are used to dealing with. Once released from the biofilm, the bacteria can be killed with antibiotics.
Kane Biotech, a company based in Winnipeg, Canada, is developing treatments and preventives based on an enzyme called Dispersin B, which was discovered in the bacterial species Actinobacillus actinomycetemcomitans but is now mass produced by the company using E. coli bacteria. Dispersin B breaks up the sugary bonds in the slime of biofilms, separating the bacteria from one another.
In animal studies, the company has reported that a combination of Dispersin B and broad-spectrum antibiotics can effectively prevent biofilm buildup in central venous catheters. (Such catheters, which are inserted into large veins in the neck, chest or groin, frequently become colonized by biofilms when bacteria make their way in from the patients' skin or from contact with healthcare workers.) Kane is also working on ways to incorporate Dispersin B into treatments for chronic wounds such as diabetic foot ulcers, which are thought to be slow-healing because of infections by biofilms.
David Davies, assistant professor of biological sciences at Binghamton University in New York, also is taking the divide-and-conquer approach. But instead of attacking biofilm slime from the outside with an enzyme, his lab is working with a chemical messenger derived from biofilms themselves.
This messenger — its name is proprietary — is common to many species of biofilm bacteria and is responsible for the dispersion effect that is a normal part of their life cycle. Davies' group intends to tweak this messenger so that it could be used as a medicine that would trick biofilms into thinking it was time to break up. Once they do so, it would make the bacteria susceptible to classical antibiotic treatments.
Biosignal, an Australian biotech company, is trying to prevent biofilms from forming on medical devices in the first place. Its product is derived from a type of seaweed called Delisea pulchra that is found off the Australian coast. Although many surfaces in the ocean are covered with biofilm, the leaves of this plant are not. That's because they produce chemicals called furanones that prevent biofilm formation.
Furanones don't kill bacteria. According to Stewart, this is ideal. By not exposing the bacteria to poisons, there is less pressure for the selection of resistant strains — a problem that has become widespread with the increased use of antibiotics.
Peter Steinberg, a professor of biological sciences at the University of New South Wales in Australia and the head of research and development at Biosignal, says that the company has found a way to produce refined versions of furanones in the lab. The company is using them to make coatings for contact lenses. A small clinical trial in Australia involving 10 patients wearing the coated contact lenses overnight showed that the furanone coating is safe and well-tolerated.
The firm is working toward larger, longer trials and is in the early stages of developing furanone coatings for medical devices such as catheters.
A group in Israel led by Gad Lavie, an assistant professor at Sheba Medical Center, is taking a more physical approach to the biological problem of biofilms on medical devices. Working with NanoVibronix, an Israeli company, Lavie has found that when scientists attach a small acoustic-wave-producing device to the outside portion of a urinary catheter, biofilm formation is prevented.
The acoustic waves cause vibrations in the catheter that are imperceptible to patients but apparently repulsive to bacteria. In a small clinical trial conducted last year in Germany, six of seven patients fitted with nonvibrating catheters in their urethras developed biofilms in them. None of the vibrating catheters showed any signs of biofilm formation.
"It was really amazing," Lavie says. These results are significant, he adds, because patients who are catheterized for long periods of time must have their catheters changed every four to five days because of biofilm buildup. He expects that vibrating catheters might not need to be replaced for months.
Biofilm research is still an emerging field. Although many approaches for dealing with biofilms in health and industrial settings have been thought up, most are still in the development stage. For now, the surest way to proceed in treating biofilms is to remove them when possible.
In hospitals, this means replacing catheters every few days. In the kitchen, it means really scrubbing produce clean. And, of course, Stewart says, "tooth brushing is a good idea."
Breeding grounds
Biofilms are not just in the human body. They can occur on any moist surface.
Fresh produce: The moist, nutrient-rich surfaces of fruits and vegetables are prime for biofilms. They can be hard to remove even with washing. This is not usually a problem unless a pathogenic bacterium, such as the strain of E. coli that was involved in the spinach recall, becomes part of the mix. Eco-Safe Systems USA is marketing a product that dissolves ozone gas in water, producing an antibacterial wash that can kill bacteria instantly, even when it is hiding in a biofilm. The ozone then breaks down to oxygen. The USDA allows produce washed with ozonated water to be labeled organic.
Industrial pipes: Biofilms can set up residence inside pipes and cause devastating corrosion. They were behind the breach found in the Alaska Pipeline last summer. Sixteen miles of pipe had to be replaced.
Household pipes: Biofilms can also build up in water pipes and air-conditioning ducts. If they grow in the pipes feeding the hot tubs, chunks of bacteria can break off, enter the hot tub and become aerosolized, leading to an infection known as "hot tub lung."
— Erin Cline
The sticky mess is called a biofilm, a slick layer of bacteria that is one of the biggest problems facing medicine today. Biofilms are forcing scientists to reevaluate their view of bacteria as free-floating bugs to one of sophisticated communities stuck on surfaces.
The National Institutes of Health estimates that more than 80% of microbial infections in the human body are caused by biofilms, many of them creating chronic and reoccurring problems. Two of the most serious: The layer of Pseudomonas aeruginosa that forms in the trachea of cystic fibrosis patients and the hospital-acquired infections resulting from biofilm formation on implanted medical devices.
Even the healthiest among us deals with biofilms on a daily basis in the form of dental plaque. And biofilms containing a pathogenic strain of E. coli were behind the spinach recall in October.
The problem with biofilms is that, because of their tightknit structure, they are resistant to traditional disinfectants and antibiotics. New research is aimed at finding ways to battle these goo-covered conglomerates. By understanding how biofilms thrive, scientists are devising new strategies for defeating them.
Biofilms form in a series of steps that scientists are just starting to understand. Step one occurs when a few bacteria attach to a surface. They activate certain genes within their genomes and inactivate others, starting their transformation from free-floaters to biofilm.
The bacteria begin to secrete polymers that hold aggregates of cells together. Then, as the biofilm grows, it becomes more complex and even starts to act like a multicellular organism.
Structures arise — such as channels to bring in nutrients and take away wastes.
Bacteria in different areas of the biofilm take on different roles. Some cells secrete enzymes, while others continue to make sticky matrix proteins. Some bacteria continue to rapidly divide, while others enter a dormant state.
The heterogeneity of biofilms is part of what makes them so robust, says Phil Stewart, director of the Center for Biofilm Engineering at Montana State University in Bozeman. A drug that can kill some of the bacteria in the biofilm might be useless against some of their neighbors.
The final step in the biofilm life cycle is dispersion. As conditions get crowded and resources become scarce, groups of cells detach and float away — potentially setting up new biofilms if they happen to land in a good spot.
"It's a little bit like seeds," Stewart says.
In many chronic and recurring infections — such as ear infections, prostatitis in men, urinary tract infections and endocarditis — these biofilm seeds set off the immune system and cause symptoms such as fever and inflammation that signal to doctor and patient that something's amiss.
When antibiotics are administered, the free-floating bacteria are killed. But the original biofilm remains unscathed. Although the infection appears to be cured, it is only a matter of time before another chunk of biofilm is set free and the symptoms return.
There are no good ways to fight biofilms because an awareness of their importance has only emerged in the last decade, Stewart says. Before that, research on bacteria focused on homogeneous cultures of fast-growing cells in flasks. Tools that fight these kinds of bacteria are great for acute infections in which bacteria are freely floating in the body. But they are almost useless against biofilms.
The Center for Biofilm Engineering is trying to change this by developing standardized methods for working with biofilms that the whole research community can use. A few companies and academic scientists are already exploring new avenues in treating and preventing biofilms.
One of the problems with today's antibiotics is that many only attack bacteria that are actively growing. This means that the dormant cells in a biofilm will escape treatment and be left behind to regrow the biofilm. So one approach to fighting biofilms is to come up with drugs that can kill all the biofilm residents.
Cubist Pharmaceuticals in Lexington, Mass., developed an antibiotic called daptomycin (marketed as Cubicin) that is able to do just that, enabling doctors to eradicate a biofilm with drug treatment.
But even if you could use antibiotics to kill all the bacteria in a biofilm, that might not be the best idea, says Wenyuan Shi, professor of oral biology and medicine at UCLA's School of Dentistry.
"Think of a lawn infested with dandelions," he says. "If you kill everything, the dandelions will come back first. But if you use a dandelion-specific killer and the grass fills in the lawn, the dandelions won't come back."
Many biofilms are composed of both good and bad bacteria. Shi's lab has developed a "smart bomb" that targets the harmful bacteria in a biofilm. A short antimicrobial peptide is attached to another one that mimics a pheromone used by bacteria to communicate. This hybrid bacteria-fighting molecule attaches to certain bacteria and makes sure only the targeted bugs are killed.
Shi has formed a Los Angeles-based company, C3Jian, to develop this technique for use in dental hygiene products. The company recently received the go-ahead for a clinical pilot study of a dental varnish that incorporates its peptides. It expects to have a product on the market in about three years.
Another approach to fighting biofilms is to try to break up their slimy coating and return them to the free-floating state that scientists are used to dealing with. Once released from the biofilm, the bacteria can be killed with antibiotics.
Kane Biotech, a company based in Winnipeg, Canada, is developing treatments and preventives based on an enzyme called Dispersin B, which was discovered in the bacterial species Actinobacillus actinomycetemcomitans but is now mass produced by the company using E. coli bacteria. Dispersin B breaks up the sugary bonds in the slime of biofilms, separating the bacteria from one another.
In animal studies, the company has reported that a combination of Dispersin B and broad-spectrum antibiotics can effectively prevent biofilm buildup in central venous catheters. (Such catheters, which are inserted into large veins in the neck, chest or groin, frequently become colonized by biofilms when bacteria make their way in from the patients' skin or from contact with healthcare workers.) Kane is also working on ways to incorporate Dispersin B into treatments for chronic wounds such as diabetic foot ulcers, which are thought to be slow-healing because of infections by biofilms.
David Davies, assistant professor of biological sciences at Binghamton University in New York, also is taking the divide-and-conquer approach. But instead of attacking biofilm slime from the outside with an enzyme, his lab is working with a chemical messenger derived from biofilms themselves.
This messenger — its name is proprietary — is common to many species of biofilm bacteria and is responsible for the dispersion effect that is a normal part of their life cycle. Davies' group intends to tweak this messenger so that it could be used as a medicine that would trick biofilms into thinking it was time to break up. Once they do so, it would make the bacteria susceptible to classical antibiotic treatments.
Biosignal, an Australian biotech company, is trying to prevent biofilms from forming on medical devices in the first place. Its product is derived from a type of seaweed called Delisea pulchra that is found off the Australian coast. Although many surfaces in the ocean are covered with biofilm, the leaves of this plant are not. That's because they produce chemicals called furanones that prevent biofilm formation.
Furanones don't kill bacteria. According to Stewart, this is ideal. By not exposing the bacteria to poisons, there is less pressure for the selection of resistant strains — a problem that has become widespread with the increased use of antibiotics.
Peter Steinberg, a professor of biological sciences at the University of New South Wales in Australia and the head of research and development at Biosignal, says that the company has found a way to produce refined versions of furanones in the lab. The company is using them to make coatings for contact lenses. A small clinical trial in Australia involving 10 patients wearing the coated contact lenses overnight showed that the furanone coating is safe and well-tolerated.
The firm is working toward larger, longer trials and is in the early stages of developing furanone coatings for medical devices such as catheters.
A group in Israel led by Gad Lavie, an assistant professor at Sheba Medical Center, is taking a more physical approach to the biological problem of biofilms on medical devices. Working with NanoVibronix, an Israeli company, Lavie has found that when scientists attach a small acoustic-wave-producing device to the outside portion of a urinary catheter, biofilm formation is prevented.
The acoustic waves cause vibrations in the catheter that are imperceptible to patients but apparently repulsive to bacteria. In a small clinical trial conducted last year in Germany, six of seven patients fitted with nonvibrating catheters in their urethras developed biofilms in them. None of the vibrating catheters showed any signs of biofilm formation.
"It was really amazing," Lavie says. These results are significant, he adds, because patients who are catheterized for long periods of time must have their catheters changed every four to five days because of biofilm buildup. He expects that vibrating catheters might not need to be replaced for months.
Biofilm research is still an emerging field. Although many approaches for dealing with biofilms in health and industrial settings have been thought up, most are still in the development stage. For now, the surest way to proceed in treating biofilms is to remove them when possible.
In hospitals, this means replacing catheters every few days. In the kitchen, it means really scrubbing produce clean. And, of course, Stewart says, "tooth brushing is a good idea."
Breeding grounds
Biofilms are not just in the human body. They can occur on any moist surface.
Fresh produce: The moist, nutrient-rich surfaces of fruits and vegetables are prime for biofilms. They can be hard to remove even with washing. This is not usually a problem unless a pathogenic bacterium, such as the strain of E. coli that was involved in the spinach recall, becomes part of the mix. Eco-Safe Systems USA is marketing a product that dissolves ozone gas in water, producing an antibacterial wash that can kill bacteria instantly, even when it is hiding in a biofilm. The ozone then breaks down to oxygen. The USDA allows produce washed with ozonated water to be labeled organic.
Industrial pipes: Biofilms can set up residence inside pipes and cause devastating corrosion. They were behind the breach found in the Alaska Pipeline last summer. Sixteen miles of pipe had to be replaced.
Household pipes: Biofilms can also build up in water pipes and air-conditioning ducts. If they grow in the pipes feeding the hot tubs, chunks of bacteria can break off, enter the hot tub and become aerosolized, leading to an infection known as "hot tub lung."
— Erin Cline
Evolution at Work: Watching Bacteria Grow Drug Resistant
Day by day, the doctors unwittingly helped the bacteria infecting their young heart patient to evolve. The more intensively they treated his affliction with antibiotics, the more the microbes resisted the therapy.
In a strict medical sense, the young man, identified only as Patient X, died of complications from a congenital heart ailment and a Staphylococcus aureus infection.
More broadly, evolution killed him.
The life-and-death struggle inside his infected heart was driven by the same evolutionary forces of natural selection and adaptation that are causing a pandemic of drug-resistant diseases world-wide. The emergence of such immunity among infectious diseases is one of the most well-documented problems in modern public health. Until now, however, researchers knew little about how bacteria multiplying inside the human body overcome the drugs designed to control them.
Patient X died in October 2000 after a 12-week hospital stay. His case comes to light now because researchers only recently developed the computational techniques needed to sequence generations of bacteria. The hospital, which also wasn't identified, gave the patient's Staph samples to the Rockefeller team for research purposes. The techniques still are too slow and expensive for clinical use.
When Patient X was admitted to the hospital, he was already suffering from a Staphylococcus aureus infection, but it was still vulnerable to antibiotics. During treatment, however, the bacteria quickly developed stronger resistance to four antibiotics, including vancomycin, the drug of last resort for intractable infections, the scientists reported. As living bacteria, the Staph were driven to survive.
Every time the patient took his medicine, the antibiotics killed the weakest bacteria in his bloodstream. Any cell that had developed a protective mutation to defend itself against the drug survived, passing on its special trait to descendants. With every round of treatment, the cells refined their defenses through the trial and error of survival. "It means that during a normal course of treatment there is an evolutionary revolution going on in your body," said Stanford University biologist Stephen Plaumbi, author of "The Evolution Explosion: How Humans Cause Rapid Evolutionary Change."
These resistant microbes, all disease-producing organisms spawned by the original infection, quickly accumulated 35 useful mutations. Each one altered a molecular sensor or production of a protein.
Researchers then matched these gradual genetic changes to increasing levels of drug resistance, shocked that it took so little to undermine the foundation of modern infectious-disease control. "We have now really looked into the belly of the beast and seen the mechanism," said Rockefeller microbiologist Alexander Tomasz.
Nearly two million people catch bacterial infections in U.S. hospitals every year and 90,000 of them die -- seven times as high as a decade ago as germs become immune to almost every antibiotic developed during the past 60 years. The most common is the Staphylococcus bacteria. World-wide, some two billion people carry these bacteria; up to 53 million people are thought to harbor antibiotic-resistant forms.
On average, people who contract Staph infections stay in the hospital three times as long and face five times the risk of dying. But these infections are becoming more prevalent outside hospitals. Antibiotic-resistant Staph infections increased almost sevenfold from 2001 to 2005, researchers reported last week in the Archives of Internal Medicine. Contagions such as tuberculosis, pneumonia and bubonic plague also are becoming immune to the drugs that once kept them at bay.
The death of Patient X highlights the speed of natural selection in fostering antibiotic resistance. "When you talk about the evolution of an arm or an eye or a species, you might be talking about millions of years. You can get bacteria resistant in a week," Dr. Mwangi said.
The Rockefeller researchers believe that a better understanding of evolution will lead to better antibiotic treatments. They want to disable the genes that allow these disease bacteria to mutate and adapt. The Staph bacteria that evolved inside Patient X now have such strong defenses that, in recent tests, they easily withstood even the next generation of clinical antibiotics. For the time being, the microbes are keeping one step ahead.
In a strict medical sense, the young man, identified only as Patient X, died of complications from a congenital heart ailment and a Staphylococcus aureus infection.
More broadly, evolution killed him.
The life-and-death struggle inside his infected heart was driven by the same evolutionary forces of natural selection and adaptation that are causing a pandemic of drug-resistant diseases world-wide. The emergence of such immunity among infectious diseases is one of the most well-documented problems in modern public health. Until now, however, researchers knew little about how bacteria multiplying inside the human body overcome the drugs designed to control them.
Patient X died in October 2000 after a 12-week hospital stay. His case comes to light now because researchers only recently developed the computational techniques needed to sequence generations of bacteria. The hospital, which also wasn't identified, gave the patient's Staph samples to the Rockefeller team for research purposes. The techniques still are too slow and expensive for clinical use.
When Patient X was admitted to the hospital, he was already suffering from a Staphylococcus aureus infection, but it was still vulnerable to antibiotics. During treatment, however, the bacteria quickly developed stronger resistance to four antibiotics, including vancomycin, the drug of last resort for intractable infections, the scientists reported. As living bacteria, the Staph were driven to survive.
Every time the patient took his medicine, the antibiotics killed the weakest bacteria in his bloodstream. Any cell that had developed a protective mutation to defend itself against the drug survived, passing on its special trait to descendants. With every round of treatment, the cells refined their defenses through the trial and error of survival. "It means that during a normal course of treatment there is an evolutionary revolution going on in your body," said Stanford University biologist Stephen Plaumbi, author of "The Evolution Explosion: How Humans Cause Rapid Evolutionary Change."
These resistant microbes, all disease-producing organisms spawned by the original infection, quickly accumulated 35 useful mutations. Each one altered a molecular sensor or production of a protein.
Researchers then matched these gradual genetic changes to increasing levels of drug resistance, shocked that it took so little to undermine the foundation of modern infectious-disease control. "We have now really looked into the belly of the beast and seen the mechanism," said Rockefeller microbiologist Alexander Tomasz.
Nearly two million people catch bacterial infections in U.S. hospitals every year and 90,000 of them die -- seven times as high as a decade ago as germs become immune to almost every antibiotic developed during the past 60 years. The most common is the Staphylococcus bacteria. World-wide, some two billion people carry these bacteria; up to 53 million people are thought to harbor antibiotic-resistant forms.
On average, people who contract Staph infections stay in the hospital three times as long and face five times the risk of dying. But these infections are becoming more prevalent outside hospitals. Antibiotic-resistant Staph infections increased almost sevenfold from 2001 to 2005, researchers reported last week in the Archives of Internal Medicine. Contagions such as tuberculosis, pneumonia and bubonic plague also are becoming immune to the drugs that once kept them at bay.
The death of Patient X highlights the speed of natural selection in fostering antibiotic resistance. "When you talk about the evolution of an arm or an eye or a species, you might be talking about millions of years. You can get bacteria resistant in a week," Dr. Mwangi said.
The Rockefeller researchers believe that a better understanding of evolution will lead to better antibiotic treatments. They want to disable the genes that allow these disease bacteria to mutate and adapt. The Staph bacteria that evolved inside Patient X now have such strong defenses that, in recent tests, they easily withstood even the next generation of clinical antibiotics. For the time being, the microbes are keeping one step ahead.
British hospitals 'among worst for superbugs'
British hospitals are among the worst in Europe for superbugs, according to figures published yesterday.
Britain was found to be the fifth worst country for superbug resistance
In a league table of 29 countries only Portugal, Malta, Cyprus and Romania have higher proportions of potentially deadly antibiotic-resistant hospital-acquired infections.
Only some forms of superbugs are resistant to antibiotics - including those known as MRSA. They are part of the staphylococcus aureus family of bacteria that can live on the skin or in the nose and can cause a range of illnesses and symptoms from boils and abscesses to life-threatening diseases such as meningitis and septicaemia.
By Bruno Waterfield and Nic Fleming
The bacteria become dangerous to patients once they enter the bloodstream and those that are resistant to antibiotics pose the greatest threat.
The European Union's Centre for Disease Prevention and Control (ECDC) report on communicable diseases ranked countries based on the proportion of S aureus infections found to be antibiotic-resistant.
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With an MRSA rate of 44 per cent, Britain was found to be the fifth worst for superbug resistance, behind countries including Greece, Slovakia, Hungary, Poland and the Czech Republic.
The ECDC study compiled data showing the trend in superbug antibiotic resistance in recent years for each country.
The amount of MRSA as a proportion of all staphylococcus aureus infections in British hospitals was unchanged between 2002 and 2005.
In contrast it fell in other countries including Slovenia, Greece and in France.
Doctors fear the spread of resistance to antibiotics could lead to problems in treating other illnesses such as pneumonia.
The ECDC says the spread of hospital-acquired infections is now the main disease threat in Europe, despite continuing concerns over tuberculosis and HIV.
The report states: "If the present rapid negative development is not halted, mankind will soon lose one of its most important weapons against infectious diseases.
"The most important threat in Europe is posed by micro-organisms that have become resistant to antibiotics."
Figures released by the Office of National Statistics in February showed the number of death certificates in England and Wales that mentioned MRSA rose 39 per cent to 1,629 between 2004 and 2005.
This is widely seen as an underestimate because other causes are often listed when MRSA could have contributed to or been the primary cause deaths. Health officials privately concede they are unlikely to hit the Government target of halving the number of MRSA cases by April.
Andrew Lansley, the shadow health secretary, said: "With 7,000 nursing posts and 9,000 beds lost in the last year, it is little wonder that we are amongst the worst countries in Europe for rates of MRSA infections."
A spokesman for the Department of Health said: "The report does not show that the UK has one of the worst infection rates in Europe.
"The table only refers to the proportion of staphylococcus aureus blood stream infections that are caused by MRSA.
"Available information indicates that the prevalence of hospital-acquired infections in the UK is similar to those of other European countries and the United States."
Britain was found to be the fifth worst country for superbug resistance
In a league table of 29 countries only Portugal, Malta, Cyprus and Romania have higher proportions of potentially deadly antibiotic-resistant hospital-acquired infections.
Only some forms of superbugs are resistant to antibiotics - including those known as MRSA. They are part of the staphylococcus aureus family of bacteria that can live on the skin or in the nose and can cause a range of illnesses and symptoms from boils and abscesses to life-threatening diseases such as meningitis and septicaemia.
By Bruno Waterfield and Nic Fleming
The bacteria become dangerous to patients once they enter the bloodstream and those that are resistant to antibiotics pose the greatest threat.
The European Union's Centre for Disease Prevention and Control (ECDC) report on communicable diseases ranked countries based on the proportion of S aureus infections found to be antibiotic-resistant.
advertisement
With an MRSA rate of 44 per cent, Britain was found to be the fifth worst for superbug resistance, behind countries including Greece, Slovakia, Hungary, Poland and the Czech Republic.
The ECDC study compiled data showing the trend in superbug antibiotic resistance in recent years for each country.
The amount of MRSA as a proportion of all staphylococcus aureus infections in British hospitals was unchanged between 2002 and 2005.
In contrast it fell in other countries including Slovenia, Greece and in France.
Doctors fear the spread of resistance to antibiotics could lead to problems in treating other illnesses such as pneumonia.
The ECDC says the spread of hospital-acquired infections is now the main disease threat in Europe, despite continuing concerns over tuberculosis and HIV.
The report states: "If the present rapid negative development is not halted, mankind will soon lose one of its most important weapons against infectious diseases.
"The most important threat in Europe is posed by micro-organisms that have become resistant to antibiotics."
Figures released by the Office of National Statistics in February showed the number of death certificates in England and Wales that mentioned MRSA rose 39 per cent to 1,629 between 2004 and 2005.
This is widely seen as an underestimate because other causes are often listed when MRSA could have contributed to or been the primary cause deaths. Health officials privately concede they are unlikely to hit the Government target of halving the number of MRSA cases by April.
Andrew Lansley, the shadow health secretary, said: "With 7,000 nursing posts and 9,000 beds lost in the last year, it is little wonder that we are amongst the worst countries in Europe for rates of MRSA infections."
A spokesman for the Department of Health said: "The report does not show that the UK has one of the worst infection rates in Europe.
"The table only refers to the proportion of staphylococcus aureus blood stream infections that are caused by MRSA.
"Available information indicates that the prevalence of hospital-acquired infections in the UK is similar to those of other European countries and the United States."
NEWS RELEASE-FDA Science Board to Meet on June 14
News Release
FOR IMMEDIATE RELEASE
P07-100
June 8, 2007
Media Inquiries:
301-827-6242
Consumer Inquiries:
888-INFO-FDA
The U.S. Food and Drug Administration's (FDA) Science Board will hold a public meeting on June 14, 2007. The board, an advisory committee to the FDA, provides the agency with expert outside advice on specific technical issues, as well as emerging issues within the scientific community, industry, and academia. Members counsel the agency on regulatory science, the formulation of an appropriate research agenda, and on upgrading FDA's scientific and research facilities.
"Science provides the foundation for FDA's regulatory decisions," said Janet Woodcock, M.D., FDA's deputy commissioner and chief medical officer. "Science and technology are creating products with enormous promise and, frequently, considerable challenges. This in-depth review of our scientific capacity is critical to assuring that FDA will continue to meet the regulatory challenges of the future."
Members of the board will address food protection, the agency's interim safety/risk assessment of melamine, a report on the Antimicrobial Resistance Monitoring System (NARMS), and an agency-wide review of FDA science. For a complete agenda, briefing documents, and a list of subject matters experts that serve as advisors to the subcommittee and their affiliations, please see: www.fda.gov/ohrms/dockets/ac/oc07.htm#ScienceBoard.
The board, chaired by Kenneth Shine, M.D., University of Texas System, Austin, is composed of nine members. Other members include: Gail H. Cassell, Ph.D., Eli Lilly and Company, Indianapolis; Susan Kay Harlander, Ph.D., BT Safety, LLC, Eden Prairie; Lonnie King, D.V.M., Centers for Disease Control and Prevention, Atlanta; Barbara J. McNeil, M.D., Ph.D., Harvard Medical School, Boston; David R. Parkinson, M.D., Biogen Idec, San Diego, Calif.; F. Xavier Pi-Sunyer, M.D., St. Luke's-Roosevelt Hospital Center, New York; Allen D. Roses, M.D., GlaxoSmithKline, Research Triangle Park, N.C.; and Larry D. Sasich, Pharm.D., consumer representative, Erie, Pa.
Last year, the board established the Subcommittee for the Review of FDA Science to determine whether the FDA's current science portfolio is properly positioned to deal new regulatory challenges stemming from developments in science and technology.
During the daylong meeting, the Subcommittee will provide an update on the progress of their review. The subcommittee, chaired by Gail H. Cassell, Ph.D., of Eli Lilly and Company, will submit a draft written report of its preliminary findings to the board this summer. The subcommittee has asked 28 scientific subject-matter experts, drawn from government, industry and academia, to contribute to the report.
The Science Board meeting is scheduled for June 14 from 8 a.m. to 4:30 p.m. at the Holiday Inn, 2 Montgomery Village Ave., Gaithersburg, Md.
Public comments can be submitted; please see the Federal Register notice for this meeting for more information: www.fda.gov/OHRMS/DOCKETS/98fr/E7-9737.htm.
####
FOR IMMEDIATE RELEASE
P07-100
June 8, 2007
Media Inquiries:
301-827-6242
Consumer Inquiries:
888-INFO-FDA
The U.S. Food and Drug Administration's (FDA) Science Board will hold a public meeting on June 14, 2007. The board, an advisory committee to the FDA, provides the agency with expert outside advice on specific technical issues, as well as emerging issues within the scientific community, industry, and academia. Members counsel the agency on regulatory science, the formulation of an appropriate research agenda, and on upgrading FDA's scientific and research facilities.
"Science provides the foundation for FDA's regulatory decisions," said Janet Woodcock, M.D., FDA's deputy commissioner and chief medical officer. "Science and technology are creating products with enormous promise and, frequently, considerable challenges. This in-depth review of our scientific capacity is critical to assuring that FDA will continue to meet the regulatory challenges of the future."
Members of the board will address food protection, the agency's interim safety/risk assessment of melamine, a report on the Antimicrobial Resistance Monitoring System (NARMS), and an agency-wide review of FDA science. For a complete agenda, briefing documents, and a list of subject matters experts that serve as advisors to the subcommittee and their affiliations, please see: www.fda.gov/ohrms/dockets/ac/oc07.htm#ScienceBoard.
The board, chaired by Kenneth Shine, M.D., University of Texas System, Austin, is composed of nine members. Other members include: Gail H. Cassell, Ph.D., Eli Lilly and Company, Indianapolis; Susan Kay Harlander, Ph.D., BT Safety, LLC, Eden Prairie; Lonnie King, D.V.M., Centers for Disease Control and Prevention, Atlanta; Barbara J. McNeil, M.D., Ph.D., Harvard Medical School, Boston; David R. Parkinson, M.D., Biogen Idec, San Diego, Calif.; F. Xavier Pi-Sunyer, M.D., St. Luke's-Roosevelt Hospital Center, New York; Allen D. Roses, M.D., GlaxoSmithKline, Research Triangle Park, N.C.; and Larry D. Sasich, Pharm.D., consumer representative, Erie, Pa.
Last year, the board established the Subcommittee for the Review of FDA Science to determine whether the FDA's current science portfolio is properly positioned to deal new regulatory challenges stemming from developments in science and technology.
During the daylong meeting, the Subcommittee will provide an update on the progress of their review. The subcommittee, chaired by Gail H. Cassell, Ph.D., of Eli Lilly and Company, will submit a draft written report of its preliminary findings to the board this summer. The subcommittee has asked 28 scientific subject-matter experts, drawn from government, industry and academia, to contribute to the report.
The Science Board meeting is scheduled for June 14 from 8 a.m. to 4:30 p.m. at the Holiday Inn, 2 Montgomery Village Ave., Gaithersburg, Md.
Public comments can be submitted; please see the Federal Register notice for this meeting for more information: www.fda.gov/OHRMS/DOCKETS/98fr/E7-9737.htm.
####
Friday, June 8, 2007
Strange but True: Antibacterial Products May Do More Harm Than Good
Antibacterial soaps and other cleaners may actually be aiding in the development of superbacteria.
By Coco Ballantyne
Tuberculosis, food poisoning, cholera, pneumonia, strep throat and meningitis: these are just a few of the unsavory diseases caused by bacteria. Hygiene—keeping both home and body clean—is one of the best ways to curb the spread of bacterial infections, but lately consumers are getting the message that washing with regular soap is insufficient. Antibacterial products have never been so popular. Body soaps, household cleaners, sponges, even mattresses and lip glosses are now packing bacteria-killing ingredients, and scientists question what place, if any, these chemicals have in the daily routines of healthy people.
Traditionally, people washed bacteria from their bodies and homes using soap and hot water, alcohol, chlorine bleach or hydrogen peroxide. These substances act nonspecifically, meaning they wipe out almost every type of microbe in sight—fungi, bacteria and some viruses—rather than singling out a particular variety.
Soap works by loosening and lifting dirt, oil and microbes from surfaces so they can be easily rinsed away with water, whereas general cleaners such as alcohol inflict sweeping damage to cells by demolishing key structures, then evaporate. "They do their job and are quickly dissipated into the environment," explains microbiologist Stuart Levy of Tufts University School of Medicine.
Unlike these traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria, Levy notes. For example, after spraying and wiping an antibacterial cleaner over a kitchen counter, active chemicals linger behind and continue to kill bacteria, but not necessarily all of them.
When a bacterial population is placed under a stressor—such as an antibacterial chemical—a small subpopulation armed with special defense mechanisms can develop. These lineages survive and reproduce as their weaker relatives perish. "What doesn't kill you makes you stronger" is the governing maxim here, as antibacterial chemicals select for bacteria that endure their presence.
As bacteria develop a tolerance for these compounds there is potential for also developing a tolerance for certain antibiotics. This phenomenon, called cross-resistance, has already been demonstrated in several laboratory studies using triclosan, one of the most common chemicals found in antibacterial hand cleaners, dishwashing liquids and other wash products. "Triclosan has a specific inhibitory target in bacteria similar to some antibiotics," says epidemiologist Allison Aiello at the University of Michigan School of Public Health.
When bacteria are exposed to triclosan for long periods of time, genetic mutations can arise. Some of these mutations endow the bacteria with resistance to isoniazid, an antibiotic used for treating tuberculosis, whereas other microbes can supercharge their efflux pumps—protein machines in the cell membrane that can spit out several types of antibiotics, Aiello explains. These effects have been demonstrated only in the laboratory, not in households and other real world environments, but Aiello believes that the few household studies may not have been long enough. "It's very possible that the emergence of resistant species takes quite some time to occur…; the potential is there," she says.
Apart from the potential emergence of drug-resistant bacteria in communities, scientists have other concerns about antibacterial compounds. Both triclosan and its close chemical relative triclocarban (also widely used as an antibacterial), are present in 60 percent of America's streams and rivers, says environmental scientist Rolf Halden, co-founder of the Center for Water and Health at Johns Hopkins Bloomberg School of Public Health. Both chemicals are efficiently removed from wastewater in treatment plants but end up getting sequestered in the municipal sludge, which is used as fertilizer for crops, thereby opening a potential pathway for contamination of the food we eat, Halden explains. "We have to realize that the concentrations in agricultural soil are very high," and this, "along with the presence of pathogens from sewage, could be a recipe for breeding antimicrobial resistance" in the environment, he says.
Triclosan has also been found in human breast milk, although not in concentrations considered dangerous to babies, as well as in human blood plasma. There is no evidence showing that current concentrations of triclosan in the human body are harmful, but recent studies suggest that it acts as an endocrine disrupter in bullfrogs and rats.
Further, an expert panel convened by the Food and Drug Administration determined that there is insufficient evidence for a benefit from consumer products containing antibacterial additives over similar ones not containing them.
"What is this stuff doing in households when we have soaps?" asks molecular biologist John Gustafson of New Mexico State University in Las Cruces. These substances really belong in hospitals and clinics, not in the homes of healthy people, Gustafson says.
Of course, antibacterial products do have their place. Millions of Americans suffer from weakened immune systems, including pregnant women and people with immunodeficiency diseases, points out Eugene Cole, an infectious disease specialist at Brigham Young University. For these people, targeted use of antibacterial products, such as triclosan, may be appropriate in the home, he says.
In general, however, good, long-term hygiene means using regular soaps rather than new, antibacterial ones, experts say. "The main way to keep from getting sick," Gustafson says, "is to wash your hands three times a day and don't touch mucous membranes."
By Coco Ballantyne
Tuberculosis, food poisoning, cholera, pneumonia, strep throat and meningitis: these are just a few of the unsavory diseases caused by bacteria. Hygiene—keeping both home and body clean—is one of the best ways to curb the spread of bacterial infections, but lately consumers are getting the message that washing with regular soap is insufficient. Antibacterial products have never been so popular. Body soaps, household cleaners, sponges, even mattresses and lip glosses are now packing bacteria-killing ingredients, and scientists question what place, if any, these chemicals have in the daily routines of healthy people.
Traditionally, people washed bacteria from their bodies and homes using soap and hot water, alcohol, chlorine bleach or hydrogen peroxide. These substances act nonspecifically, meaning they wipe out almost every type of microbe in sight—fungi, bacteria and some viruses—rather than singling out a particular variety.
Soap works by loosening and lifting dirt, oil and microbes from surfaces so they can be easily rinsed away with water, whereas general cleaners such as alcohol inflict sweeping damage to cells by demolishing key structures, then evaporate. "They do their job and are quickly dissipated into the environment," explains microbiologist Stuart Levy of Tufts University School of Medicine.
Unlike these traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria, Levy notes. For example, after spraying and wiping an antibacterial cleaner over a kitchen counter, active chemicals linger behind and continue to kill bacteria, but not necessarily all of them.
When a bacterial population is placed under a stressor—such as an antibacterial chemical—a small subpopulation armed with special defense mechanisms can develop. These lineages survive and reproduce as their weaker relatives perish. "What doesn't kill you makes you stronger" is the governing maxim here, as antibacterial chemicals select for bacteria that endure their presence.
As bacteria develop a tolerance for these compounds there is potential for also developing a tolerance for certain antibiotics. This phenomenon, called cross-resistance, has already been demonstrated in several laboratory studies using triclosan, one of the most common chemicals found in antibacterial hand cleaners, dishwashing liquids and other wash products. "Triclosan has a specific inhibitory target in bacteria similar to some antibiotics," says epidemiologist Allison Aiello at the University of Michigan School of Public Health.
When bacteria are exposed to triclosan for long periods of time, genetic mutations can arise. Some of these mutations endow the bacteria with resistance to isoniazid, an antibiotic used for treating tuberculosis, whereas other microbes can supercharge their efflux pumps—protein machines in the cell membrane that can spit out several types of antibiotics, Aiello explains. These effects have been demonstrated only in the laboratory, not in households and other real world environments, but Aiello believes that the few household studies may not have been long enough. "It's very possible that the emergence of resistant species takes quite some time to occur…; the potential is there," she says.
Apart from the potential emergence of drug-resistant bacteria in communities, scientists have other concerns about antibacterial compounds. Both triclosan and its close chemical relative triclocarban (also widely used as an antibacterial), are present in 60 percent of America's streams and rivers, says environmental scientist Rolf Halden, co-founder of the Center for Water and Health at Johns Hopkins Bloomberg School of Public Health. Both chemicals are efficiently removed from wastewater in treatment plants but end up getting sequestered in the municipal sludge, which is used as fertilizer for crops, thereby opening a potential pathway for contamination of the food we eat, Halden explains. "We have to realize that the concentrations in agricultural soil are very high," and this, "along with the presence of pathogens from sewage, could be a recipe for breeding antimicrobial resistance" in the environment, he says.
Triclosan has also been found in human breast milk, although not in concentrations considered dangerous to babies, as well as in human blood plasma. There is no evidence showing that current concentrations of triclosan in the human body are harmful, but recent studies suggest that it acts as an endocrine disrupter in bullfrogs and rats.
Further, an expert panel convened by the Food and Drug Administration determined that there is insufficient evidence for a benefit from consumer products containing antibacterial additives over similar ones not containing them.
"What is this stuff doing in households when we have soaps?" asks molecular biologist John Gustafson of New Mexico State University in Las Cruces. These substances really belong in hospitals and clinics, not in the homes of healthy people, Gustafson says.
Of course, antibacterial products do have their place. Millions of Americans suffer from weakened immune systems, including pregnant women and people with immunodeficiency diseases, points out Eugene Cole, an infectious disease specialist at Brigham Young University. For these people, targeted use of antibacterial products, such as triclosan, may be appropriate in the home, he says.
In general, however, good, long-term hygiene means using regular soaps rather than new, antibacterial ones, experts say. "The main way to keep from getting sick," Gustafson says, "is to wash your hands three times a day and don't touch mucous membranes."
Battle-Hardened Bacteria
When Andrew Speaker boarded an Air France flight for Paris last month carrying a form of extensively drug-resistant tuberculosis, he became a global pariah--both for the lethal bug in his system and for the folly of exposing other people to it. But while Speaker may have been reckless, the blame for the emergence of drug-resistant bugs like the one he is incubating falls partly on the rest of us. For years public-health officials have been raising the alarm about how our overreliance on antibiotics is breeding a generation of superbugs, increasingly resistant to the medicines designed to kill them. The problem has only gotten worse as antibiotic use has expanded to agriculture, where cattle, chicken and fish are routinely treated with the drugs to keep infectious diseases in check.
According to the Centers for Disease Control and Prevention, more than 70% of the bacteria that cause infections in hospitals are resistant to at least one antibiotic. Methicillin-resistant Staphylococcus aureus (MRSA), which causes boils or pimples on the skin, is only the latest superbug to make the rounds and has appeared in dozens of high school and college athletic locker rooms, as well as in three NFL locker rooms. Drug-resistant tuberculosis cases, including those of the variety affecting Speaker, have risen along with peaks in AIDS cases, as people with weakened immune systems are especially vulnerable to infection with multiple bugs.
The only way to thwart the bacteria, say public-health officials, is to curb the use of antibiotics. That's not likely to happen, with antibacterial hand sanitizers now in handy pocket packs and few folks willing to tough out a throat or ear infection without pharmaceutical help. The more the bugs come into contact with such agents, the faster bacteria find ways to mutate around them.
And that points to a fundamental weakness of current antibiotics. All exploit the fact that the best agents to kill bacteria come from other bacteria. Each species makes toxins that can either kill other species or arrest their growth, and existing antibiotics are modified versions of these natural defenses. But that is just the kind of biological arms race that microbes and other living things excel at adapting to. So researchers working on the next generation of antibiotics are taking advantage of new knowledge about bacterial genetics and a better understanding of the resistance process to stay one step ahead of the ever changing bugs.
One way to do this is to confuse the bacteria, hitting them with not just one natural toxin but two. At Vertex Pharmaceuticals in Cambridge, Mass., scientists are developing a new class of antibiotics that targets a pair of enzymes the microbes depend on to copy their genes and reproduce. Adapting in two directions at once slows down the bacteria enough to give the drug time to work. "Mathematically, it becomes much harder for the bacteria to develop resistance to different targets at the same time," says Dr. John Alam, the company's chief medical officer.
Another strategy is to ambush the bacteria with an unlikely ally: viruses. Vincent Fischetti at Rockefeller University is enlisting the help of bacteriophages, viruses that infect only bacterial cells, leaving human ones alone. They hijack the bacterium's genetic machinery and within minutes start to pump out hundreds of copies of themselves. When enough progeny build up inside the cell, the phages produce an enzyme that chews through the cell wall, causing it to explode with the force of a popping champagne cork and spew out the viral intruders.
Treating humans with live viruses--even ones that shouldn't harm us--is always risky, so Fischetti decided to isolate just the bacteria-puncturing enzyme and use it to kill bacteria from the outside. So far, he has developed compounds against pneumococcus, streptococcus and anthrax and hopes to eventually treat infected patients by squirting the enzymes in nasal-spray form weekly.
None of these agents are quite ready for the pharmacy yet, and until they are, researchers are focusing on new ways to maximize the power of drugs we do have. By studying bacterial DNA, scientists at the Naval Research Laboratory are decoding the genetic battle plans that the bugs use to develop resistance. These secrets can help doctors prescribe antibiotics more effectively by knowing which strains are most susceptible to which drugs.
As the TB scare reminded us, that's important in a world in which superbugs can quickly go global. Bacteria may be resourceful things, but science, while slower, can be smarter. It's just a matter of knowing your enemy--and packing the right weapons. [This article contains a complex diagram. Please see hardcopy or pdf.] USING A VIRUS TO ATTACK BACTERIA 1 A bacteriophage is a virus that infects bacteria but not human cells
Bacteriophage
Genes
2 It inserts its genetic material into a bacterial cell
Bacterium
Viral genes
3 The bacterium is hijacked into producing new viruses
4 After about 45 minutes, the viruses produce a lytic enzyme, which causes the bacterial cell wall to burst
5 The enzyme can be purified from these viruses or manufactured to be used as an antibiotic-like agent to kill bacteria
Lytic enzyme
Ruptured bacterial cell wall
Source: Vincent Fischetti, Ph.D., Rockefeller University
TIME Diagram by Joe Lertola
According to the Centers for Disease Control and Prevention, more than 70% of the bacteria that cause infections in hospitals are resistant to at least one antibiotic. Methicillin-resistant Staphylococcus aureus (MRSA), which causes boils or pimples on the skin, is only the latest superbug to make the rounds and has appeared in dozens of high school and college athletic locker rooms, as well as in three NFL locker rooms. Drug-resistant tuberculosis cases, including those of the variety affecting Speaker, have risen along with peaks in AIDS cases, as people with weakened immune systems are especially vulnerable to infection with multiple bugs.
The only way to thwart the bacteria, say public-health officials, is to curb the use of antibiotics. That's not likely to happen, with antibacterial hand sanitizers now in handy pocket packs and few folks willing to tough out a throat or ear infection without pharmaceutical help. The more the bugs come into contact with such agents, the faster bacteria find ways to mutate around them.
And that points to a fundamental weakness of current antibiotics. All exploit the fact that the best agents to kill bacteria come from other bacteria. Each species makes toxins that can either kill other species or arrest their growth, and existing antibiotics are modified versions of these natural defenses. But that is just the kind of biological arms race that microbes and other living things excel at adapting to. So researchers working on the next generation of antibiotics are taking advantage of new knowledge about bacterial genetics and a better understanding of the resistance process to stay one step ahead of the ever changing bugs.
One way to do this is to confuse the bacteria, hitting them with not just one natural toxin but two. At Vertex Pharmaceuticals in Cambridge, Mass., scientists are developing a new class of antibiotics that targets a pair of enzymes the microbes depend on to copy their genes and reproduce. Adapting in two directions at once slows down the bacteria enough to give the drug time to work. "Mathematically, it becomes much harder for the bacteria to develop resistance to different targets at the same time," says Dr. John Alam, the company's chief medical officer.
Another strategy is to ambush the bacteria with an unlikely ally: viruses. Vincent Fischetti at Rockefeller University is enlisting the help of bacteriophages, viruses that infect only bacterial cells, leaving human ones alone. They hijack the bacterium's genetic machinery and within minutes start to pump out hundreds of copies of themselves. When enough progeny build up inside the cell, the phages produce an enzyme that chews through the cell wall, causing it to explode with the force of a popping champagne cork and spew out the viral intruders.
Treating humans with live viruses--even ones that shouldn't harm us--is always risky, so Fischetti decided to isolate just the bacteria-puncturing enzyme and use it to kill bacteria from the outside. So far, he has developed compounds against pneumococcus, streptococcus and anthrax and hopes to eventually treat infected patients by squirting the enzymes in nasal-spray form weekly.
None of these agents are quite ready for the pharmacy yet, and until they are, researchers are focusing on new ways to maximize the power of drugs we do have. By studying bacterial DNA, scientists at the Naval Research Laboratory are decoding the genetic battle plans that the bugs use to develop resistance. These secrets can help doctors prescribe antibiotics more effectively by knowing which strains are most susceptible to which drugs.
As the TB scare reminded us, that's important in a world in which superbugs can quickly go global. Bacteria may be resourceful things, but science, while slower, can be smarter. It's just a matter of knowing your enemy--and packing the right weapons. [This article contains a complex diagram. Please see hardcopy or pdf.] USING A VIRUS TO ATTACK BACTERIA 1 A bacteriophage is a virus that infects bacteria but not human cells
Bacteriophage
Genes
2 It inserts its genetic material into a bacterial cell
Bacterium
Viral genes
3 The bacterium is hijacked into producing new viruses
4 After about 45 minutes, the viruses produce a lytic enzyme, which causes the bacterial cell wall to burst
5 The enzyme can be purified from these viruses or manufactured to be used as an antibiotic-like agent to kill bacteria
Lytic enzyme
Ruptured bacterial cell wall
Source: Vincent Fischetti, Ph.D., Rockefeller University
TIME Diagram by Joe Lertola
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