Antibiotic-Coated Medical Devices Could Cut Infections

In the future, hospital patients may have a new weapon to fight infection after surgery: powerful antibiotic coatings attached to implants, catheters, surgical instruments and other medical devices. Researchers at the University of Southern Mississippi say they've developed a way to attach penicillin, and potentially other antibiotics, to these types of devices.

Almost 2 million patients in the United States get an infection in the hospital each year, and about 90,000 of those patients die each year as a result of their infection, according the U.S. Centers for Disease Control and Prevention (CDC). Many of these infections are linked to medical devices. But, "modifying [device] surfaces to adhere penicillin kills bacteria," explained lead researcher and professor of polymer science Marek W. Urban. "The penicillin is able to destroy the colony of bacteria," he said.

Urban's team has found a way to modify the surface of poly(tetrafluoroethylene), a material similar to Teflon, so that penicillin sticks to it and remains highly active. This polymer is used in medical procedures ranging from blood vessel grafting to plastic and reconstructive surgery. The trick was to modify the surface of poly(tetrafluoroethylene) so that arms would stick out from the surface, which the penicillin could stick to, and that would, in turn, surround bacteria and kill it, Urban said.

In their experiments, expected to be published in the Feb. 12 issue of the journal Biomacromolecules, the researchers showed that these penicillin-coated surfaces could effectively kill Staphylococcus aureus, a bacterium responsible for many serious infections.

However, since more than 70 percent of the bacteria that cause hospital-acquired infections are resistant to at least one of the antibiotics most commonly used to treat them, Urban's group is hoping to find other antibiotics that are able to coat the surfaces of medical devices. In addition, the researchers are also working on modifying other types of surfaces to hold on to antibiotics.

"We want to develop coatings that can be applied to any surfaces to kill bacteria, Urban said. "This is the first step. The trick is to make the antibiotic remain active after it is attached," he said. One expert believes this may be a breakthrough in reducing the number of hospital-acquired infections.

"It is a very good idea to affect surfaces not only to have an antimicrobial in place there, but also to disrupt bacterial activity," said Dr. Philip Tierno, the director of clinical microbiology and immunology at New York University Medical Center and author of The Secret Life of Germs. "Most artificial materials, when they are placed in or on the body, serve as a platform for the growth and proliferation of bacteria," he said. This is a big problem with catheters, Tierno noted. "It seems that this method could cut down on infections, but you really have to test the hypothesis," he said. "However, based on this paper, it appears that you can disrupt the growth of bacteria by coating the surface of devices."

January 19, 2007 (HealthDay News)

Staph Bug Causes New Pneumonia

WASHINGTON (Reuters) - A nasty staph germ circulating in and out of hospitals produces a poison that can kill pneumonia patients within 72 hours, researchers said on Thursday.

Staphylococcus aureus bacteria - or S. aureus - can pass one another the gene for the toxin and are apparently swapping it more often, the researchers report in Friday's issue of the journal Science. The toxin, called Panton Valentine leukocidin or PVL, can itself cause pneumonia and can kill healthy tissue.

Luckily, people infected with the bacteria quickly develop a high fever and astute doctors can identify it, said Gabriela Bowden of the Texas A&M Health Science Center in Houston, who led the study.
"This is a scary situation. We are trying to put the word out and to educate people about it," Bowden said in a telephone interview.

S. aureus is the most common cause of hospital-acquired infections, and can cause inflammation of the heart, toxic-shock syndrome and meningitis. A new strain called MRSA resists the antibiotic methicillin, but it can be treated with antibiotics like doxycycline and vancomycin. An outbreak of methicillin-resistant S. aureus carrying the new toxin killed two patients in a British hospital in December with a new type of pneumonia called necrotizing pneumonia. This infection destroys lung tissue and also kills some of the immune system cells sent to battle it.

Dr. Marina Morgan, consultant medical microbiologist at Exeter Nuffield Hospital in Britain, said the PVL toxin "turbo-charges" an already dangerous bacteria. "PVL is strong enough on its own to destroy the lungs," she said in a statement. And the toxin is immune to antibiotics. "The reason most patients die is that despite killing the bug, PVL toxins already formed continue to digest lung tissue, so we desperately need some way of removing the toxins," Morgan said.

S. aureus, which commonly live on the skin and cause pimples, boils and other minor infections, can cause a serious wound if the toxin-producing strains get into a cut.

Old-fashioned hygiene is the best line of defense, Bowden said. "This is a community-associated strain, which means that in schools, the kids can carry it. Anybody can be colonized with it," she said. "I tell my kids if you scrape your knee, go to the bathroom immediately and wash it with soap." Hospitals must impose strict hygiene to control it.

Bowden's team tested the PVL-producing Staph on mice and found that two days after infection, their lungs were filled with immune cells and lung tissue was starting to bleed and die. A stretch of DNA known as a cassette carries the code for the PVL toxin. Such a little segment is easily passed from one strain of bacteria to another, said Bowden, and viruses called bacteriophages can also carry them.

Understanding how this happens could provide a way to develop new drugs or vaccines and shed light on how bacteria acquire new and dangerous qualities.

"The appearance of PVL toxin in severe Staphylococcal pneumonia is a recent phenomenon. Previously the toxin was only found in less than 5 percent of strains," said Dr. Ronald Cutler of the University of East London. Some companies are working on staph vaccines but none is on the market.

By Maggie Fox, Health and Science Editor

Law Calls for Mandatory Education and Penalties

A new health insurance law calls for mandatory education for healthcare workers and penalties for employees and facilities that don't comply with infection prevention measures, which health officials are developing.

State Senator Richard T. Moore, an Uxbridge Democrat who is chairman of the Health Care Financing Committee, filed legislation yesterday that eventually would require health officials to make public the infection rates for individual hospitals, and state health officials said public disclosure probably would be part of any new reporting requirements placed on hospitals.

Because hospitals are not required currently to report hospital-acquired infections to public health agencies, researchers don't know how often they occur. But patient safety and public health specialists estimate that nationally hundreds of thousands of hospital patients a year contract infections. Bacteria spread down tubes, also called central lines or catheters, placed in their veins to deliver medicine or in their lungs to help them breathe, and through incisions made during surgery.

The Federal Centers for Disease Control and Prevention estimates that each year patients contract 250,000 infections from catheters alone, infections that kill between 12 percent and 25 percent of patients who get them and cost about $25,000 each to treat. A small Massachusetts study published in 2002 suggested that 13 percent of 1,953 cardiac bypass patients suffered infections at the site of their surgery, including ones detected after patients were discharged.

Aside from the risk to patients and the cost to the healthcare system, another reason for the industry's growing focus on the problem is the increasing proportion of hospital infections that are resistant to common antibiotics, which makes them more dangerous and difficult to treat. At the same time, specialists believe that many infections are preventable with proper sterilization techniques and timely administration of antibiotics and more judicious use of catheters and ventilators.
"Hospital-acquired infections lead to significant harm to patients and significant unnecessary cost in the healthcare system," said John McDonough, executive director of the consumer advocacy group Health Care For All, which is also pushing legislation to require hospitals to reduce infection rates. "A variety of folks across Massachusetts are attempting to draw more focus on this problem so Massachusetts can assume a strong leadership position and perhaps be one of the first states to drive rates down to zero."

Hospitals are required by several federal agencies and organizations to have infection-prevention programs and have been monitoring their rates internally and trying to lower them for years. But the 2006 law that requires all Massachusetts residents to have health coverage by this July included $1 million for the Massachusetts Department of Public Health to implement a mandatory statewide infection prevention program in healthcare facilities. The program will begin in hospitals.
Health officials recently hired an outside consulting company to oversee development of the program and appointed advisory boards to make recommendations on how to collect incidence data from hospitals and what specific infection-control practices should be put in place and monitored, said Paul Dreyer, director of the Division of Health Care Quality. He said health officials probably will be ready to implement the program in a year.

The department has authority to discipline hospitals for poor infection-control practices, but health officials generally know about problems only if they get a complaint, which Dreyer said they rarely do.

"For a long time, there's been a sense that hospital-acquired infections are inevitable and the cost of doing business," Dreyer said. "Partly because of the patient safety movement, people don't think that's the right way of looking at them anymore. They're no more the cost of doing business than wrong-side surgery."

This shift in thinking has been reinforced as some hospitals have shown it's possible to reduce infection rates to near zero by focusing more on prevention. Michigan hospitals that rigorously implemented infection-control procedures, such as doctors and nurses washing their hands and cleaning patients' skin with an antibacterial agent before inserting intravenous lines, reduced catheter-related blood stream infections in intensive-care patients from an average of 7.7 per 1,000 days of catheter usage to 1.4 per 1,000 days a year and a half later, researchers reported in the New England Journal of Medicine last month. And 32 hospitals in Pennsylvania reported in October 2005 that they reduced catheter-related infections 68 percent through similar measures.

"One of the keys to making health reform work and getting people to buy and maintain health insurance is to keep costs down without necessarily cutting out" benefits , Moore said. "One of the biggest ways to do this is to prevent infections that occur in hospitals and drive up the costs. Most of it is preventable. We'll be able to save some money and save some lives."
He said public reporting will give hospitals added incentive to improve their infection rates. Several states, including Pennsylvania and Missouri, now require hospitals to publicly report their rates.

Paul Wingle, a Massachusetts Hospital Association spokesman, said the group will work with Moore on his bill to make sure that appropriate infection data is publicly reported. "There's no philosophical barrier to it," he said. "It's all a question of how it's done."

Doctors warn that coming up with ways to fairly compare hospitals through public reporting will be a challenge, partly because hospitals that look harder for problems may have higher rates but not necessarily have more infections. Rates also must be adjusted for patient risk factors, such as obesity.

Last month, Beth Israel Deaconess Medical Center president Paul Levy posted his hospital's rates for central line-related infections on www.runningahospital.blogspot.com, in part to spur other hospitals to be more transparent about their quality of care. Bacteria on the tubing can flow quickly through the bloodstream and to major organs, making these infections of particular concern.

The hospital's rate was about 3 central line infections per 1,000 patient days about a year and a half ago. Since then, the rate has dropped to an average of 1.5 central line infections, hospital executives said.

Dr. Kenneth Sands, vice president and medical director for healthcare quality, said the hospital started requiring healthcare workers to follow specific procedures for inserting catheters and to document each step, for example, covering the patient's entire body with sterile cloth, rather than just the area immediately around the catheter site.

Beth Israel Deaconess also began investigating each infection as a major event, rather than just collecting data, a key shift in thinking. "We think we saved some lives from our intervention," he said.

By Liz Kowalczyk, Globe Staff
January 11, 2007

Contact Isolation in Practice in S.C.

Piedmont Medical Center in South Carolina is at the head of a national charge to prevent the spread of the antibiotic-resistant staph supergerm MRSA.

For now, people visiting Piedmont's critical care patients must wear sterile gowns and latex gloves until patients are found to be free of the MRSA germ. The practice, which started in August, will expand to the rest of the hospital, possibly by the end of January.

MRSA, or Methicillin-Resistant Staphylococcus Aureus, is spread by skin-to-skin contact. People who are ill or whose immune systems are compromised are more susceptible than healthy people. For them, it can lead to pneumonia and other serious infections, including in the bloodstream or at surgical sites. The germ can be deadly.

Piedmont's battle against MRSA begins with "contact isolation," which involves placing the patient in a room and taking a nasal swab test for the germ. It takes about 48 hours to get results. Meanwhile, hospital staff and visitors to the room must wear disposable gowns and gloves, which immediately afterward are placed in a disposal bin.

"I think we're doing what everybody else should be doing," said Dr. Craig Charles, Piedmont's infectious disease specialist. "We're trying to stop it in its tracks. "Research has shown if you put a greater effort to identifying it and take precautions to prevent it from spreading, you can prevent people from getting it and reduce the pain and suffering," he said.

Assuming the test returns negative, visitors no longer have to wear gowns and gloves. It is recommended that they return to normal precautions of washing hands or using an antibacterial lotion when entering and leaving the patient's room. If the test returns positive, an antibiotic ointment is used in the patient's nose and under the nails. The patient takes baths in chlorhexadine soap. After 10 days, the MRSA infection should be eradicated.

Visitors aren't tested for the germ because the hospital only has legal authority to test patients. A major goal of contact isolation is preventing visitors from carrying the germ from a patient's room to hospital public areas.

PMC is in a consortium with the Duke Infection Control Outreach Group of Duke University Medical Center in Durham, N.C. Those in the consortium share information on MRSA and compare data. "Probably in the future, more hospitals are going to try to do this," said Dr. Deverick Anderson, an infectious disease fellow at Duke. "At this point, most hospitals only do it in specific situations. A lot of focus is on critical care areas."

In October, the U.S. Centers for Disease Control and Prevention issued new guidelines "to halt the rising rates of drug-resistant infections" with "aggressive steps." The guidelines cover all drug-resistant bacteria, but they cite MRSA as "a good example" of a germ with increasing antibiotic resistance. It refers to MRSA as "a growing problem in hospitals and health-care facilities."

The Institute for Healthcare Improvement has recommended "contact isolation" while testing for MRSA, Anderson said. The association just released a campaign called "Five Million Lives" to decrease harm to patients when hospitalized. Active surveillance for MRSA is one of six targets.

Anderson called MRSA "definitely one of the worst infections you can get in a hospital."

"There's a new type emerging in the past four or five years that is causing skin infections," he said. "We would hope to come up with ways to control it, but right now, it's headed in the wrong direction." Fifteen years ago, only people who spent significant time in a hospital got MRSA, Charles said. Then cases emerged in athletic teams and other communities outside hospitals, and standard antibiotics didn't work.

It is bacteria's nature to evolve for survival. "If you keep pressuring them with antibiotics, they will keep evolving," Charles said. Penicillin was a wonder drug when it was invented, but the medical community ultimately discovered it didn't kill staph germs. Methicillin was developed as the anti-staph penicillin. In the mid-1980s, MRSA developed resistance to methicillin.

Another antibiotic, Vancomycin, was developed to combat MRSA. Charles said there now are cases in Japan where MRSA is Vancomycin-resistant. There have been six such cases in the United States, Anderson said. "It's a moving target," he said.

Ironically, some bacteria have evolved to the point they are no longer resistant to older antibiotics that have not been used for a while, Charles said. However, MRSA is not one of them.

Bacteria live in colonies, and most family and friends have been exposed to the same colonies of bacteria. Therefore, visitors do not have to wear face masks, and hugging patients in contact isolation is OK.

Clothing and hands, especially hands, are major carriers. Hands spread germs to doors, counters and elevator buttons, and on throughout the hospital. Hospital staff recommend washing the hands or using a sanitary lotion every time you enter or leave a patient's room, regardless of whether the patient is in contact isolation.

Piedmont has not yet identified unusual clusters of MRSA. If it does, it will research common circumstances for the source. Like most hospitals, Charles said, Piedmont has had isolated cases where MRSA contributed to a patient's death.

PMC is studying the cost of buying disposable gloves and gowns that contain an impenetrable plastic. The gloves and gowns would be distributed to staff and visitors at the 288-bed hospital. A box of 100 gloves costs $4.24 and gowns $7.80 for a package of 10, said hospital spokeswoman Myra Joines. For a critical-care patient, staff use an estimated 50 gowns and 100 gloves a day. That does not include visitors. Hospital officials expect it to be well worth the expense.

"It's the right thing to do," Charles said. "Every dollar spent on infection control saves $5 and countless lives. If you prevent one serious hospital-acquired illness, you pay for the whole program."

By Karen Bair - The Herald, Rock Hill, South Carolina - Updated 12/24/06

Nightmare Scenario is Real ...

MRSA is already notorious for killing the elderly and frail. But now a new form of the 'hospital superbug' is spreading through our parks and playgrounds. You can catch it with a single scratch, and the drugs that used to hold out some hope are rapidly becoming useless. Sarah Boseley reports

Children gash their legs and graze their elbows. It's normal. Usually they recover incredibly fast. Occasionally, if the wound starts to look a little dodgy, they may be given an antibiotic - just in case it's infected. But in Texas, increasing numbers of healthy kids with the ordinary childhood lacerations from falling out of trees or being pushed over in the playground are being admitted to hospital. And some of them never make it home.

They are victims of what has been described as the largest bacterial epidemic in the world. Behind it is the superbug - MRSA - a variant of a common-or-garden bacteria, staphylococcus aureus, which no longer responds to the usual antibiotics, such as methicillin. In the UK, the superbug is notorious for attacking frail, elderly, very sick people in hospital. In Texas, it is killing healthy children.

Matthew Ykema, 14, arrived at Texas Children's Hospital in Houston with a swollen, throbbing knee, a temperature of 40C and a strange greyish hue to his skin. "They didn't expect me to live through the night," he said.

He had picked up a new form of MRSA that is passing from hand to hand and from playing field to swimming pool in parts of the United States. This "community-acquired MRSA", or CA-MRSA, throws out a toxin called PVL - Panton-Valentine leukocidin - that destroys white blood cells. Bacteria are harmless on the skin, but CA-MRSA can be deadly if it gets into the bloodstream through a cut.

Zacharias Nunley, aged seven, was admitted to another Houston hospital, the Memorial Hermann Children's Hospital, with excruciating pains in his leg. He had no visible injuries. Doctors again diagnosed MRSA, and said that the blood clot caused by the infection could have killed him. It was three months before he could leave hospital. "I said, 'How did he get it? Do I need to throw away my furniture? Was it the food?'," his mother, Charla Rigsby, told the Houston Chronicle. "They said, 'No ma'am, the bacteria is everywhere. There's no telling where he got it.' That's what really, really, truly bothered me."

With the financial backing of the charitable Vivian L Smith Foundation, Texas Children's Hospital has been studying the rise of CA-MRSA since 2000 and has clocked up more than 5,000 cases in all ages - some of them babies less than a month old. The bug infects soft tissue but also bone. Around 200 people have had invasive infections such as necrotising pneumonia, which causes abscesses in the lungs. When PVL causes this type of pneumonia, around 75% of patients die. Most don't last more than about four days.

PVL toxins are also produced by ordinary staph aureus, which is not resistant to methicillin and can be relatively easily treated. But deaths from PVL-producing MRSA have now been confi rmed around the globe, from Australia to the UK. Part of the problem is that these are young people who are not expected to get ill, so the infection is not identified quickly. In October 2004, a young Royal Marine recruit called Richard Campbell-Smith scratched his legs running through gorse bushes 28 weeks through his 32-week training course at the commando training centre in Lympstone, Devon. He was only 18, he was super-fit, but he was never to recover. He felt cold and feverish and three days later collapsed on the floor by his bed. He died of necrotising pneumonia.

Marina Morgan, of the Royal Devon and Exeter Hospital where he was treated, said that although cases were rare, they were difficult to detect and more might be slipping through. "It is the worst bug I have ever seen and people really need to know about it," Dr Morgan said at the inquest. "It is untreatable. It multiplies very quickly. One bug will multiply into 17 million within 24 hours. Usually signs include pneumonia, coughing up blood and very high temperatures, but not everyone will look for it."

Since then, there has been a fatal oubreak of PVL-producing MRSA at a hospital in the West Midlands. Maribel Espada, a 33-year-old nurse undergoing a caesarian section, died, as did another patient in the same hospital, while four others had skin infections such as abscesses and boils. A further two tested positive for the bug. It was the first time that this particularly lethal strain of MRSA had been detected in a hospital setting, where the potential to do harm to vulnerable sick people is enormous.

This looks like a new killer in our midst. In fact, it's not. It's an old bug in a new, deadly garb. PVL-producing staph aureus was first identified in the 1930s. Before 1960, nearly 60% of all staph aureus infections were PVL-producing. Then the introduction of methicillin - a new class of antibiotic to replace the failing penicillin - just about wiped it out. But just about wiping out bacteria is the worst thing you can do. Those that remain come back with a vengeance.

Bacteria are the greatest survivors on the planet. They have been around for three billion years. Like viruses, they adapt to circumstances. If some, but not all, of them are wiped out by an enemy - such as methicillin - any that survive mutate into a form that can resist methicillin. And then they multiply.

What we have with the spread of PVL producing MRSA is another triumph for the world of germs. One antibiotic after another has been rendered almost useless as the bugs mutate to overcome them. This was understood by Alexander Fleming, the discoverer of penicillin. But through the 50s and 60s, as doctors joyfully stamped out infections from tuberculosis to pneumonia and some declared the battle against infectious diseases won, most people expected a constant stream of new antibiotics to replace those that fell by the wayside.

It hasn't happened. Staph aureus bacteria developed resistance to penicillin, the cephalosporins, the fluoroquinolones such as ciprofl oxacin and methicillin; then, in 2002, the first case of resistance to the last-resort drug vancomycin was reported in the US. We are now running on empty and facing what Richard James, director of the Centre for Healthcare Associated Infections at Nottingham University, calls "the post-antibiotic apocalypse".

"We are facing a future where there will be no antibiotics and hospital will be the last place to be if you want to avoid picking up a dangerous bacterial infection," he says. "In effect, cut your finger on Monday and you'll be dead by Friday if there's nothing to prevent it."

James has been rebuked by Christine Beasley, the Department of Health's chief nursing officer, for his crisis talk. She says it is scare-mongering. But he and other scientists say that something must be done urgently to find new weapons against the bugs around us that are regaining the upper hand they had in the pre-drug age.

How have we come to this pass? Two things have happened. We have over-used and ill-used existing antibiotics in a cavalier fashion in the past, expecting another one to come along at any time. A decade ago, for example, every mother who took a sniffling son to the GP came out with a prescription for antibiotics, even though colds and flu and sore throats are caused by viruses, not bacteria, so antibiotics have no effect on them. We, the patients, demanded antibiotics as a cure-all. They, the doctors, handed them out because they would get a hard time if they didn't.

Most of the drug companies, meanwhile, no longer have any interest in hunting down new antibiotics because it's not financially worthwhile. Roche has dropped antibiotic research, while GlaxoSmithKline, BristolMyersSquibb and Eli Lilly have all cut down. The only company to have entered the field is Novartis.

"Virtually all the pharmaceutical companies that were interested in developing antibacterials have pulled out of research in the field," says Richard Wise, who heads the government's specialist advisory committee on antimicrobial resistance.

"We had a plethora of drugs in the 70s to the 90s. In the last two years, only one new agent has come along, called linezolid. The reasons are fairly straightforward. If you were the chief finance officer of a major drug company, you would far rather put your research pounds into developing drugs that were going to be used on a chronic basis for diseases like Alzheimer's, schizophrenia or ulcers, where people have a lifetime's illness."

Drugs such as statins for heart disease are a goldmine - urged on everybody with any sign of heart disease and potentially on an entire generation. And they will be told to keep taking the tablets for life. A course of antibiotics is rarely more than seven days.

And the very reason that we need new antibiotics is a disincentive for the drug companies to invent them. Resistance always sets in. The useful lifespan of the drug will be much shorter than that of any painkiller or antidepressant. The industry claims it costs $800m (£407m) to develop a single new drug - although critics say that figure contains marketing and advertising spend as well as the costs of the many drugs that fall by the wayside. They are unlikely to get the sort of profit their shareholders want in five to 10 years for drugs that matter so much but are used for such a short time - even if the companies set an astronomical price.

"The fact that disease-causing bacteria soon become resistant to any antibiotic has further reduced the interest of pharmaceutical companies in funding the research required to discover new antibiotics and bring them to the market," says Professor James. "They would rather concentrate on developing drugs for 'lifestyle' conditions such as high blood pressure or diabetes that patients need every day to control their health."

The first antibiotics that were discovered after penicillin now appear to have been the easy ones. Even in the glory days of the 1960s, the new drugs coming along were aunts, uncles and cousins of those we already had. And the trouble with families is that a bacteria can become resistant to the whole lot. What are needed now are new classes of antibiotics, and there have been only two in recent times - Wyeth's linezolid, licensed in 2001, and daptomycin from Novartis, licensed in 1997. And researchers found some resistance to linezolid even in the clinical trials to prove its effi cacy.

According to Sir Anthony Coates, professor of medical microbiology at St George's school of medicine in London, there are 18 potential antibiotic drugs at various stages of development. If that sounds promising, compare it with nearly 100 drugs for cancer that are in the very last phase of trials prior to licensing - let alone all the others queueing behind in the pipeline. "That gives you a feel for what's in store in the next five to 10 years," says Professor Coates. Basically, not much.

He is worried about other bacterial infections. Most of the upcoming drugs are aimed at the bug everybody knows, the ubiquitous MRSA, for which we still have the last-resort antibiotic vancomycin. MRSA is part of a group that share certain characteristics called gram-positive bacteria and includes listeria, streptococcus and clostridium (clostridium difficile infections in hospital are rising very fast and causing more deaths than MRSA).

But there is another group called gram-negative bacteria. They include E coli, pseudomonas and acinetobacter and - although they are less common and usually found in the gut rather than on the skin - they can cause infections that are now untreatable. A bacterium called klebsiella is the best known of the pseudomonas family and seems to be a particular danger for patients with cystic fibrosis. Yet there is even less on the way to treat these infections.

This is a global phenomenon, well illustrated by the dramatic comeback of a disease that was the scourge of 19th-century Britain. Consumption - the "white death", which we know today as tuberculosis - is now once again a deadly threat and far, far harder to treat than a few decades ago. First we saw the rise of multi-drug resistant TB (MDR-TB). The germ had evolved to overcome the two most powerful antibiotics used to treat it, isoniazid and rifampicin. Confirmation of the seriousness of the situation came in 1991, with a major outbreak of MDR-TB in the hospitals of New York City. A survey revealed that 19% of TB in the city was resistant to the two drugs.

If that wasn't bad enough, last year a small study presented to the International Aids conference in Toronto put the world on alert for the next inevitable stage of the fi ghtback of the TB bacillus against modern drugs. TB has spread through Africa on the back of the HIV epidemic, because of the damaged immune systems of those with the virus. Doctors found a pocket of XDR-TB - extremely drug resistant TB - in South Africa. These were people with HIV who swiftly died of a form of TB that was resistant not only to isoniazid and rifampicin but also to any fluoroquinolone and at least one of the remaining injectable drugs to treat the disease: capreomycin, kanamycin and amikacin. A study by the World Health Organization estimates that possibly almost as many as one in fi ve cases of "multi-drug-resistant" TB is actually "extremely drug-resistant" TB. This type is still treatable in countries where the whole drug arsenal is available (it is not in Africa), but only 50-60% of patients survive.

With apocalypse on the horizon - according to Professor James - what is to be done? First of all, continue to cut down on antibiotic use by GPs. Now every surgery has notices pointing out the pointlessness of pills for coughs and colds.

There has been a crackdown of sorts on farmers, too - at least within the EU. Antibiotics were sold as growth promoters until the mid-90s. What they really did was stop battery hens and overcrowded animals getting disease. "Shut 25,000 chickens in a shed and close the windows and you can spread infection among them very quickly," says Richard Young of the Soil Association. "We fought a long campaign to get these things banned."

But they were not banned outside Europe, and while countries are forbidden from selling us meat from animals given banned antibiotics, it is very difficult to detect.

Bacteria being as smart as they are, resistance has naturally developed in animals, too. And although scientific proof is short on the ground, Young is not alone in believing that genes from resistant bugs in the meat at our table may mix in our gut with genes from antibiotics we may be taking. In the US, the animal antibiotic virginiamycin was banned for fear that cross resistance might develop to the similar human antibiotic synercid.

Although the medical and veterinary world is on red alert to preserve the failing power of the antibiotics that remain, Professor James says more could be done. He cannot believe the government is doing little more than urge better hospital cleaning and hand-washing.

"Why isn't the government doing something?" he asks. "We are talking about hospitalacquired infection which kills at least 5,000 a year, whereas about 3,000 die in road traffic accidents."

Dangerous bacteria are passed around in hospital and enter wounds through surgical instruments and catheters and the like - but they also come in with the patients and the visitors. "We don't screen on admission," says James. "That is the critical thing."

He says screening would show up an alarmingly high rate of bacterial infection and would have serious financial consequences. "They don't want to know the answer. What would they do with all these people?" Hospitals would need to be redesigned with many more single rooms for isolation. But it happens in other European countries.

Meanwhile, university academics are looking for new ways to tackle the bugs that are increasingly defeating standard antibiotics. "There may be another way," says Professor Coates. Bacteria, he says, can be easily killed by antibiotics while they are multiplying - so their defence mechanism is to stop multiplying for a while. Then, when the threat has died down, they may come back with a vengeance. Coates and his colleagues have designed an antibiotic cream that will give the non-multiplying bacteria a sledgehammer blow, designed to act very fast and hard. "No mercy," he says. "They are all dead." It has taken him 25 years of research. The new drug, which he hopes can be used on wounds in hospitals and in the nose - where bacteria collect - before patients go into surgery, is about to go into clinical trials.

Elsewhere, scientists are coming up with other new strategies, such as drugs that will disable bacteria and render them harmless rather than trying to kill them outright. The theory is that bacteria may not struggle against them as hard as they do in the primitive fight for survival. And there have long been hopes for bacteriophages - naturally occurring viruses that can infect and kill bacteria. But there are only a couple of companies looking at the possibility of harnessing them for use in healthcare, and for all the enthusiasts, there are equal numbers of sceptics who fear that bacteria could just as quickly evolve to resist phages, as they do antibiotics.

Most scientists cannot see a way forward unless the mighty pharmaceutical industry puts its collective shoulder back to the wheel. And it won't do that unless it is off ered a few financial incentives and perhaps a shortcut when it comes to the red-tape for licensing new antibiotics. Professor James says that government must intervene - but acknowledges that any solution to the coming crisis will not be found within the career span of any of today's politicians.

Matthew Ykema was lucky. He is now fit and well. But Texas Children's Hospital has put out warnings to parents, telling them they should "closely watch even the most minor scrapes, bites and injuries for signs of serious infection". Practise good hygiene, it says. "Don't allow your children to share towels or workout clothes with anyone." We're entering a whole new postantibiotic era - and it's scary.

Know your enemy: Some of the most common drug-resistant bugs

MRSA: There were 18,273 cases of staphylococcus aureus infection reported to the Health Protection Agency in the UK in 2005; more than a third - 39.2% - were MRSA (resistant to methicillin). Vancomycin is the drug now used against in such cases, but resistance to this has been detected in the US.

CLOSTRIDIUM DIFFICILE: 51,690 cases in people aged 65 and over in 2005. It causes more deaths than MRSA - 1,300 in 2004 compared with 360 deaths from MRSA. It is susceptible to antibiotics, however - metronidazole and vancomycin are the main ones used.

PVL-PRODUCING MRSA: Some of the staph aureus that produces the toxin PVL can be treated by the antibiotic methicillin but some is resistant. These bacteria are still rare - only 2% of all staph aureus - and in the UK are still normally sensitive to other antibiotics such as tetracycline and ciprofloxacin. The more common the bug becomes, the more likely it is that resistance will develop to other antibiotics.

ENTEROCOCCUS: 904 cases of infection resistant to glycopeptide (the class that includes vancomycin) were reported in 2005.

E COLI: There were 17,215 cases in England and Wales in 2005, 8-9% of which were resistant to cefotaxime and ceftazidime, 19.2% were resistant to ciprofloxacin and 7.6% resistant to gentamicin.

GONORRHOEA: 18% of cases were resistant to penicillin in 2005, up from 11.4% in 2004, and 22% were resistant to ciprofloxacin.

Wednesday January 17, 2007
The Guardian, UK

Hospital Crackdown Beating Superbug

MRSA cases are down in Huddersfield, UK latest figures show. Hospital bosses say it is because strict measures have been put in place to tackle the super-bug infection. Only 20 cases have been recorded in nine months at Huddersfield Royal Infirmary and Calderdale Royal Hospital.

The drop comes after Calderdale and Huddersfield NHS Foundation Trust - which runs the two hospital sites - celebrated a 30% reduction the year before when their MRSA rate dropped from 40 cases in 2004/5 to just 28 in 2005/6. The Trust now looks set to have another record year.

Carole Hallam, lead infection control nurse for the Trust, said: "We have a robust infection prevention and control programme and infection control is given a constant high priority in our Trust. "However, we are never complacent and the work continues across all departments." She said a number of measures had been introduced which included screening patients when they arrived at hospital and moving those found to be MRSA carriers into side rooms.

Alcohol hand gel dispensers at every bedside and training in handwashing had also helped improve the figures.
Greater infection control awareness among both staff and visitors was also helping to keep infection at bay.

The figures come after the Government set all hospital trusts a target in 2004 to halve their MRSA rates by 2008.

A new weapon against MRSA is being developed with more than £3 million of funding from the Wellcome Trust, Britain's leading research charity. Scientists have identified a class of compound that kills the superbug by preventing its ability to divide and multiply. They hope the drugs, code-named CDI 936 cell division inhibitors, will provide a safe alternative to traditional antibiotics. Theoretically they could work against all antibiotic-resistant strains of Staphylococcus bacteria, which include MRSA.

By avoiding the destruction of protective "friendly" bacteria in the gut, which are often targeted accidentally by antibiotics, they may also prevent secondary infections by other bugs. Clostridium difficile, one such bacterium, is becoming an even bigger problem than MRSA after taking advantage of the "open door" provided by antibiotics.

The Wellcome Trust today announced it was pumping £3.5 million into developing the new compounds. The grant to the Oxford-based biotech company Prolysis is one of the first awards from the charity's £91 million Seeding Drug Discovery initiative, which aims to turn promising scientific ideas into practical treatments.

HOSPITAL infections, including MRSA, are said to kill around 5,000 UK patients each year. The MRSA Support Group maintains that the true figure is closer to 20,000. MRSA, or methicillin-resistant Staphylococcus aureus, is difficult to treat because of its resistance to antibiotics. It first appeared in the 1960s and new strains emerged in the 1980s that have caused outbreaks of infection in hospitals throughout the world. MRSA most commonly attacks patients who have undergone operations and can be fatal if it triggers blood poisoning.

There were 3,517 reports of blood-stream infections from MRSA in acute NHS trusts between October 2005 and March 2006.
MRSA is most commonly spread via hands and equipment, and sometimes through the environment.

January 15, 2007
By The Huddersfield Daily Examiner

Cure for MRSA Near?

British scientists say they have found a way to destroy deadly hospital superbugs such as MRSA with drugs already on the market. Researchers have discovered that three compounds used to treat other illnesses can also batter down the defences of even the toughest antibiotic-resistant bugs.

It is hoped that the drugs – which are being kept a closely-guarded commercial secret – will be in use on NHS wards within three years. Normally, a new treatment could take almost a decade to pass through the regulatory system. But, because these compounds are already being used on humans and so are known to be safe, the early stages of testing can be bypassed. The breakthrough was hailed as a “tremendous boost” for patients.

Because of the secrecy, the full nature and names of the drugs, which are chemically very similar, are being referred to only by the code name ETS1153. All that is known about them is that they are currently used to treat some types of acute conditions.

However, the team behind the project is so confident of success that they are ready to begin large-scale clinical trials – the last step before full approval. Professor Malcolm Young, who is leading the work, said the discovery was made while testing existing drugs against MRSA on a unique computer model. The practice of putting old therapies to new use, called “repurposing”, is becoming increasingly popular in medical research.

One of the best-known examples is thalidomide, the once notorious anti-morning sickness pill blamed for birth defects which is now used against some cancers. Prof Young said: “We were looking for any compound, old or new, to do a very specific job with MRSA. “Effectively, we got lucky in that we found a compound already doing a job in a completely different area – we already know it’s safe.”

He made the discovery while working with the Newcastle-based company e-Therapeutics. The professor, who is also pro-vice-chancellor of Newcastle University, used his background in mathematics to develop systems to analyse the effects of drugs on superbugs.

He said that, when staff tested the drugs in the laboratory, they were “delighted” with results which proved that even the most resistant strains of MRSA were killed. They also knocked out other dangerous bacteria, such as vancomycin-resistant enterococci and Staphylococcus epidermidis, which are an increasing menace in hospitals, by attacking the proteins that allow the infections to grow.

Prof Young said old-fashioned laboratory methods had so far failed to offer a solution to the superbug crisis.
He added: “These new therapies for MRSA and other dangerous hospital-based infections are a tremendous boost for our new approach”. Dr Roy Drucker, medical director of e-Therapeutics, said: “We’re very encouraged by this medically important success”.

The breakthrough was applauded by Tony Field, chairman of the group MRSA Support, which assists victims of the bug and their families. He said: “This is very good news. Anything which helps in this way is to be welcomed.”

But he added that hospitals and medical staff should not drop their guard. Until the laboratory breakthrough becomes reality, he emphasised that the best way to combat superbugs is through controlling infection. “We want to see a change in hospital cleaning regimes – to do the job properly with disinfectants and not detergents,” he added.

Cases of MRSA and other infections caused by antibiotic-resistant bacteria are rising year on year, with a 24-fold increase in MRSA-linked deaths over the last decade in England and Wales, according to the Office for National Statistics.

Hospital infections, including MRSA, are said to kill about 5,000 patients a year in Britain, although MRSA Support maintains the figure is closer to 20,000. Earlier this month, it emerged that a Government promise made in 2005 to cut MRSA infection rates in half by 2008 will not be kept. Even extending the deadline to 2009 would not be enough, and a leaked government memo appeared to suggest that superbugs were out of control. The memo also revealed that cases of infection of another bug, Clostridium difficile or C. diff, had become “endemic” throughout the health service.

Although an estimated 1,000 of the superbug deaths are blamed on MRSA, it is feared that C. diff could be an even bigger problem – more than 64,000 patients were struck down with it last year.

January 17, 2007
By Mark Blacklock

Hospital Infection Rates to be Posted Online

Excerpts from the Eagle Tribune, Andover, New Hampshire
January 16, 2007

New Hampshire hospitals will be required to make information on infections patients get while being treated there available under a new law that takes effect July 1.

The law requires every hospital in the state to report the number and type of hospital-acquired infections to the state Department of Health and Human Services. Officials there will be responsible for collecting and analyzing the information and creating a database that consumers can access from the Internet to compare infection rates by hospital.

Officials hope the regulations will reduce what is a leading cause of death in the United States, while giving consumers more information to help them choose a hospital.

"We believe once (hospitals) see what their infection rates are, they're going to want to do something about it," said Lisa McGiffert, director of Consumers Union's "Stop Hospital Infections" campaign.

The Centers for Disease Control and Prevention estimate that 2 million people get infections from hospital stays every year. That's about 10 percent of the total number of hospital patients nationwide. Advocates of the new law think that by reporting the information and publicizing it, hospitals will do more to reduce infections, which kill 90,000 people a year. "Imagine if 90,000 people died from bird flu," said Rep. Howie Lund, R-Derry, one of the bill's sponsors. "The whole world would be on alert. But this is kept so quiet."

There is no federal requirement or standard by which hospitals must report this information, so states are left to set their own. Including New Hampshire, 15 states have laws requiring hospitals to report infection rates. So far, only three states - Florida, Missouri and Pennsylvania - have made the data available to the public.

"This will enable the consumer public to make a better, more informed decision about whose hands they're going to put their life into," said former Keene state Rep. Bob Guida, one of the bill's sponsors.

Currently, New Hampshire's 32 hospitals aren't required to report any information on hospital-acquired infections to the state. But data Guida gathered and analyzed while arguing the bill showed that 400 people die from hospital-acquired infections every year, and about 4,000 people get them.

"More than one person a day dies from hospital-acquired infections in our state right now," Guida said. "Hospitals don't want it known because it reflects a laxity in standards."

But reporting infection rates isn't as simple as it may seem, according to Andrea Alley, director of communications for the New Hampshire Hospital Association, which represents all of the state's hospitals. She said that even though it is now a law, hospitals can't gather the information because there are no standards by which to do so.

"Though we want to be able to provide the information, it's not useful for anybody because you're not comparing apples to apples," Alley said. "Everyone is using different criteria to define an infection. They're using different methods of even keeping track."

She said while hospitals can look at ways to prevent infections, they can't do much about reporting infections until the state tells them how. That means it will be at least a year before consumers have access to this information.

If no guidance on defining infections is provided by the federal government by July 1, the state will put rules in place for reporting infections, Department of Health and Human Services spokesman Greg Moore said.

But it won't be easy. "Everyone would agree that this is good policy," Moore said. "But the devil is in the details." Not only will the state have to get hospitals to agree on standards, they'll have to put people in charge of collecting and analyzing the results, which Moore said could be expensive. Plus, there are downsides to making this information public, he said.

"We don't want to stigmatize a hospital because they tackle the hard cases," Moore said. "We could end up in a situation (where) there's an appearance that what's going on there is resulting in a high rate of infection." But preventing infection in hospitals, advocates of the law argue, is as simple as doctors washing their hands.

"It's about being meticulous about cleanliness," Consumers Union's McGiffert said. "It doesn't cost a lot of money to do these things. And in the long run, it could end up saving the state money. "If there is higher quality, and that quality results in savings, the state will benefit financially," Moore said. "Fewer sick people just cost less."

By Courtney Paquette , Staff Writer
Eagle-Tribune

The Killer in the Locker Room

By: Christopher McDougall, Men's Health

If it weren't so real, so tragic, and such a Critical wake-up call, it could be a sick joke: Ricky Lannetti, 21 years old and tough as a truck tire, was killed by a pimple on his butt.

He'd noticed the little welt last fall, when he was dressing for football practice at Lycoming College in Williamsport, Pennsylvania. It was right under the back strap of his jock and getting a little raw, but he sure as hell wasn't going to ask the trainers to look at a pimple, not while other guys were waiting to have real injuries wrapped and taped.

Besides, apart from that, he felt great. As a senior and a starting wide receiver for Lycoming, Lannetti was having the best season of his life: He set a school record with 16 catches in a game, then the following week broke the record for catches in a season. The next Saturday, he snagged five balls as the Warriors won in overtime to advance in the playoffs. The next Saturday, he was dead.

What was found in Lannetti's blood was a "superbug," an especially aggressive type of bacterial infection called MRSA. Until recently, few family doctors had ever seen methicillin-resistant Staphylococcus aureus, and even fewer people had died of it. But over the past year, it has spread so quickly--and mutated into such frighteningly powerful strains--that even paramedics now know it by its phonetic nickname: "Mersa."

"Two years ago, it was completely unheard of," says Greg Moran, M.D., an infectious-disease specialist at the UCLA school of medicine. His E.R. has seen an "amazing" increase in MRSA cases. "Of the people who come in with skin infections, 64 percent have MRSA," he says. "It's remarkable how fast it's become one of the most common things we see."

Recent estimates by the Centers for Disease Control and Prevention (CDC) place the number of people hospitalized with communiyt-acquired MRSA annually at approximately 130,000. "The majority of the infected seem to be men," says Dr. Moran, "although no one knows why. It's such a new thing, there's not a whole lot of published information out there." So little is known about this sudden surge in MRSA cases that Dr. Moran is leading a nationwide study of skin infections seen in emergency rooms. Until then, he says, "we're learning on the fly."

Just 10 years ago, chronically ill patients in hospital settings accounted for most MRSA infections. Kidney-dialysis patients, burn victims, and HIV-AIDS sufferers were among the high-risk groups, because their immune systems were weak and they took such heavy doses of strong antibiotics that their bodies became veritable petri dishes for the growth of superbugs. And even if they weren't growing their own germs, these patients often had bedsores that allowed bacteria to worm their way in.
But now, MRSA is turning up most among the people who'd least expect to get it: young, healthy men who are often in very good shape. Last year, several members of the Miami Dolphins, including star linebacker Junior Seau and kickoff-return ace Charlie Rogers, were infected with MRSA. Seau and Rogers had to be hospitalized, as did Tampa Bay Buccaneer Kenyatta Walker and the Cleveland Browns' Ben Taylor, who needed an emergency operation to beat the infection.

It's not just pro athletes who've been hit: Five members of a fencing team in Colorado were also stricken, as were two high-school wrestlers in Indiana, 10 college football players in Pennsylvania, and two more in California. Although no quantitative studies have broken down the MRSA outbreak by gender, the CDC has found that the majority of new infections are among young men who share some kind of skin-to-skin contact, such as through sports. Outbreaks have also been reported among military recruits (235 cases were diagnosed at one basic-training site in the South), gay men, police cadets, and prisoners. All those men recovered, but many needed hospitalization and heavy antibiotics.

"You don't even need direct contact to become infected," points out Barry Kreiswirth, Ph.D., the director of the Public Health Research Institute Tuberculosis Center. "Staph has been spread in locker rooms by towel snapping. If he's got turf burn on his leg and you've got the bacteria on the towel, he can become infected."

And the more MRSA spreads, the more aggressive it seems to become. Not long ago, a person infected with staph would show up in a doctor's office with nothing worse than an abscess. But by 1999, MRSA had killed four otherwise healthy children in North Dakota and Minnesota. By December 2003, it was strong enough to kill Ricky Lannetti.

"He called Tuesday and said he was throwing up, but it wasn't that bad," recalls Ricky's mother, Theresa Lannetti, who looks like a grown-up cheerleader with her gentle smile and gymnast-lithe appearance. First thing the next morning, Ricky dragged himself to the school clinic. "Just a stomach bug," the nurse said, and sent Ricky back to his dorm. On Thursday, Theresa called the football trainer to check on her son, which led to a visit to a local doctor for blood work. But Theresa didn't wait for the results: When she heard Ricky was still feverish on Friday, she drove 5 hours through a blizzard to reach him. The Lannettis are as tough as they come--after raising three kids on a secretary's salary, Theresa joined the Philadelphia Police Academy at age 39--so she knew if her son was hurting this badly, it wasn't a touch of the flu.
When she arrived at Ricky's dorm, she was shocked. Ricky was deathly pale, and so weak his roommate had to carry him downstairs. He had a raging thirst and kept gulping Gatorade, even though he hadn't urinated in days.

By the time they got to Williamsport Hospital, Ricky was vomiting blood. Every specialist in the hospital crowded into his room, but they were all mystified: They were looking at a muscular young man with zero medical history whose body was acting like that of an ailing geriatric. The doctors tried one antibiotic, then another, and another, until Ricky had five in his system, but he was still burning with fever and passing blood through his catheter. The hospital called for a medevac chopper to fly him to an infectious-disease unit in Philadelphia, but just that fast, it was too late: Within hours, Ricky's vital functions were shutting down. His kidneys went, then his liver, and when surgeons tried to keep his heart beating with a catheter, they lost him.

"I couldn't believe this was happening," says Theresa. She'd just seen Ricky slamming his 5'9", 170-pound body all over the field a few days before, and now he was lying dead on a gurney and no one could explain how it had happened. A few days later, however, the coroner discovered two things: Ricky had MRSA in his blood and a tiny red welt on his buttocks. "He told me the infection must have spread from that little pimple," Theresa says.

"We're seeing more people who've been infected with abscesses on their buttocks, and the truth is, we don't know why," says Kreiswirth. It might be because a larger, fleshier area is more vulnerable to soft-tissue sores, or because the buttocks tend to be more damp with sweat and less exposed to air, but that's just speculation. "Until we understand more about how this staph operates," says Kreiswirth, "we won't know why it seems to favor certain parts of the body . . . or why one person will get a boil, and another will die."

Until MRSA came along, the game plan of Staphylococcus aureus was pretty simple: If four guys play two-on-two hoops, statistically one of them will be a staph carrier, since more than 30 percent of all humans have the bacteria in their noses at any time. You could be a carrier your entire life, though, and never know it: For staph to become a problem, you'd have to be carrying a strain that's strong enough to cause infection and have it come in contact with a break in someone's skin. Ironically, that skin could be your own--a carrier can infect himself, by wiping his nose and then touching an open cut.

"What's new is that some of the strains carry a toxin that destroys white blood cells," says Frank Lowy, M.D., a professor of medicine at Columbia University school of medicine who is studying staph colonization. "If you get staph under your skin, a white blood cell eats the bug, and that's the end of it. But this bug easily kills the white blood cell, which attracts more white blood cells. Eventually, a pus pocket builds up, allowing the bacteria to survive."

Like most of its contagious cousins, MRSA also has three great loves: humidity, skin cuts, and a weakened immune system. The opportunity for infection increases dramatically when these factors come together, perfect-storm-style, as they do in a gym. Locker rooms are damp and steamy, that game of two-on-two can lead to cut lips and scraped knees, and an exhausting workout temporarily lowers the body's resistance. Add to that workout gear that may not have been washed in days and you have the bacterial version of the Playboy grotto.

"If you're active and do anything that would traumatize the skin, you're potentially at risk," says David Gilbert, M.D., a past president of the Infectious Diseases Society of America (IDSA). "I've had professionals, lawyers, doctors, who have all gotten boils from this strain." Fortunately, none died, but they all required stronger antibiotics than Dr. Gilbert is comfortable giving--not because of what they'll do to the patients but because of what they're doing to the bacteria. That's the catch-22: Powerful antibiotics are needed to kill MRSA, but using them will eventually create an even more lethal version of the bug.

"It's natural selection at work," says Dr. Lowy. "There will always be mutant bacteria the antibiotic can't kill, and these may develop into a more virulent strain." And unfortunately, as antibiotics have become more prevalent--not just in doctors' offices but also in our food supply--we've sped up this evolution. For example, methicillin is the big-gun antibiotic that came after penicillin, but its current effectiveness is summarized in MRSA's name: methicillin-resistant.

We still might be holding staph infections in check if pharmaceutical companies hadn't shifted their R&D focus; instead of constantly trying to concoct updated antibiotics, says Dr. Gilbert, they turned more of their attention toward erectile dysfunction, hypertension, and heart disease. The IDSA reports that, as of 2002, "Bristol-Myers Squibb Company, Abbott Laboratories, Eli Lilly and Company, and Wyeth all halted or substantially reduced their anti-infective discovery efforts." Over the past 30 years, in fact, only three new classes of antibiotics have been developed, and resistance to one emerged before the FDA had approved it.

Nevertheless, it's hard to fault the drug companies, Dr. Gilbert says. "Why spend a billion dollars on a drug that a patient will take for only 2 weeks, when you can spend the same money on a product he'll take for the rest of his life?" On top of that, antibiotics can quickly become obsolete. Pfizer could take 10 years to get an anti- biotic developed and approved, only to see it become defunct in 2. It's doubtful the penis will ever become resistant to Viagra.

Right now, the "drug of last resort" in MRSA cases is Vancomycin. Already, there have been three cases of Vancomycin-resistant MRSA. "That's very troubling," says Dr. Lowy. "The genetic information for this resistance can be transferred from one strain to another. And if that happens, we're facing a potential crisis over the next 5 years." There are other antibiotics, but they're not always available and can't beat all infections, warns Dr. Lowy. "Vancomycin is our workhorse, but it doesn't have the legs for a long race."

On a sweltering July afternoon 7 months after Ricky Lannetti's death, one of his buddies from high school, 20-year-old Derek Talley, was preparing to take a postworkout soak in a kiddie pool behind his Philadelphia home when he saw a sore spot on his right thumb. "Must've gotten stung by something," Talley figured. He ignored it. But over the next few days, his entire hand began to swell. He went to the hospital, where they gave him Benadryl and sent him home.

That night, his hand ached so badly, he couldn't sleep. He returned to the E.R., and this time he was admitted and put on antibiotics. The next morning, his infection was even worse. The doctors then made a long Z incision in Talley's hand to drain the abscess, and put him on stronger antibiotics. "That should take care of it," he was told.

It didn't. By his second morning in the hospital, the infection had spread further. His doctors were getting worried, so they ordered a more extensive round of blood work. When they received the results, they sat down to brief Talley. "Have you ever heard of MRSA?" they asked. He nearly fell off the bed. "Yeah," he responded. "It killed my buddy."

He was immediately started on Vancomycin, every 12 hours around the clock, two IV bags a day. Because the infection was in his hand, the doctors told him, it was especially dangerous, since it had nowhere to travel but straight up toward his heart. Talley remembered something Ricky's mother had told him: "If Ricky could have made it through that first day in the hospital, he would have been okay."

So when Talley woke the next morning, he felt he was already winning. He checked his hand; for the first time in a week, it was back to normal size. For him, the Vancomycin worked. He would still need extensive physical therapy; a month after his touch-and-go week in the hospital, he had recovered only 75 percent of his hand function.

Surprisingly, the greatest source of hope in the fight against MRSA may come from the most common defense: soap and water. By making sure to wash their hands thoroughly and by keeping all cuts well disinfected and bandaged, most people can avoid spreading or contracting MRSA. "It's not going away," Dr. Lowy says, "but we have a chance of slowing it until new antibiotics, or even a vaccine, are created."

The NFL has begun sponsoring hygiene workshops for players and is encouraging trainers to disinfect hot tubs and showers regularly, according to Steve Antonopolus, ATC, head of the NFL's Trainers' Association. "There's a potential for MRSA to be everywhere in the locker room," he says. "Around trash cans, in cleats--everywhere."

Meanwhile, the IDSA has been lobbying Congress to treat MRSA like a terrorist threat. It proposes a "10 Most Wanted" list of bacterial infections, so that any drug company that goes after one would be rewarded with a "bounty" of tax breaks and extended patents. One Florida company, Nabi Biopharmaceuticals, is already in phase three of clinical trials of a staph vaccine, which would immunize recipients. A request for FDA approval is expected by the end of 2005.

"At this point, we project it for use only among high-risk candidates, like kidney patients," says Nabi spokesman Mark Soufleris. "But potentially, it could be used for millions of people." Best of all, Soufleris points out, it could take a tremendously long time before MRSA develops resistance to the vaccine. "Antibiotics attack the bacteria at one point of entry, but our vaccine creates antibodies that attack at multiple points."

Dr. Gilbert likes what he's heard about the Nabi vaccine. "Won't that be great, to get a shot and never worry about staph again?" he says. Till then, he urges, do what your mom always told you: "Change your clothes, wash your hands, and no roughhousing."

Fighting Surgical Wound Infections

According to Catherine Statz, RN, BSN, MPH, a nurse performing surgical wound-infection surveillance for the Surgical Infectious Disease service at the University of Minnesota Department of Surgery in Minneapolis, one antiseptic is safer and more efficacious than those used historically for treating surgical wounds.

The Centers for Disease Control and Prevention (CDC) estimates that 27 million surgical procedures are performed each year in the United States with 756,000 surgical-site infections. Many of these surgical-site infections result in open wounds. It is not unusual for large wounds to remain open, to heal poorly, to be colonized with bacteria, and to remain infected for long periods.

The treatment of open wounds with topical agents that have broad-spectrum microbicidal activity is becoming increasingly important and desirable—especially before additional surgery can be done. Plastic surgeons are responsible for managing a significant percentage of colonized or infected open wounds.

The current treatment of many open wounds consists of operative debridement, parenteral antimicrobial agents, frequent dressing changes, and topically applied agents aimed at reducing microbial populations within the wound. The topical application of agents—other than sterile saline solution—on open wounds has remained controversial, as discussed below.

Typical Topical Agents

Saline is not antimicrobial, yet it is the only topical treatment used on most open or infected postoperative wounds. Treatment with saline alone significantly increases microbial titers, according to the report of a 1989 randomized emergency-department trial, in which contaminated traumatic open wounds were treated with sterile saline, povidone–iodine, or dry gauze. In that trial, the wounds were covered with gauze soaked with saline or povidone–iodine; for the control group, only dry gauze was used.

Quantitative cultures were run before and after treatment. The only significant trend was an increase in bacterial counts in the saline-soaked wounds after treatment (a 50-fold increase, compared to the controls). This effect was greater with higher initial levels of bacterial contamination. The group that was treated with saline had a higher wound-infection rate than the other groups.

Saline irrigation of open wounds is another common treatment. But irrigation as typically delivered—even with voluminous amounts of saline solution—removes little but surface contamination. Saline irrigation in the operating room (OR) should not be relied upon to completely reduce bacterial contamination, although it does remove debris, foreign material, and clots—all of which often contain bacteria—from surgical wounds.

An in vitro study showed that saline irrigation reduced colony counts of Staphylococcus aureus, S. epidermidis, and Escherichia coli by 12%–56%. However, the reduction in colony numbers was not always statistically significant, and even when it was, the amount of reduction was not clinically significant.

Chlorhexidine gluconate is the active ingredient in many antiseptic formulations, and it is used in dilute solutions for wound care. A 1988 study found little or no adverse impact to patients at concentrations of 0.05%–4%. The study also found that chlorhexidine gluconate does not appear to deter wound healing; its cytotoxic effect on fibroblasts in vitro does not exist in vivo. The study also showed that patients in the chlorhexidine gluconate group healed significantly faster than those in the saline-treated group.

A 1992 burn-unit study found chlor­hexidine gluconate to be toxic to cultured human fibroblasts; thus, it recommended that chlorhexidine gluconate should not be used before making cultured skin grafts.

In the United States, few formulations are available that can be used on open wounds. Most 4% chlor­hexidine gluconate formulations contain alcohol and detergents that can cause irritation, so they are not used on open wounds. Even so, dilutions of this formulation are widely used with positive results.

Acetic acid, which has an antimicrobial effect, has been used to treat open, infected wounds as long ago as 1778, during the American Revolution. Today, it is primarily used for wounds infected with Pseudomonas spp. Solutions of 0.25% acetic acid are estimated to decrease bacterial counts by only 20%. One in vitro trial showed that a 0.0025% solution (a factor of 100 less concentrated than the generally used dilution) of acetic acid lacked toxicity to fibroblasts but could inhibit only P. aeruginosa.

A 1985 comparison of the bactericidal and cytotoxic effects of serial dilutions of acetic acid showed that its cytotoxicity outweighed its bactericidal potency. Therefore, acetic acid is considered by many health care professionals to deter wound healing and should not be used. Moreover, its bactericidal ability is only selective.

Hypochlorite was first used to treat open wounds in France in 1825. In 1915, Dakin introduced a solution of 0.5% sodium hypochlorite that was used to disinfect open wounds during World War I. Now called Dakin solution, it is still used today, but its cytotoxicity makes it unsuitable for use in wound care.

However, bactericidal, noncytotoxic dilutions of sodium hypochlorite have been identified. McKenna and Lineaweaver showed 0.005% dilutions of sodium hypochlorite to be noncytotoxic yet bactericidal; such dilutions are 100 times less concentrated than the 0.5% solution that is commonly used in wounds. A study of capillary circulation of granulation tissue concluded that, “Hypochlorite solutions may be sufficiently toxic to preclude their clinical value.”

Iodine use on wounds was first reported in 1839. Iodine was used successfully during the US Civil War to treat open wounds. Molecular iodine can rapidly penetrate the cell walls of microorganisms; however, exactly how it kills living cells is not known.

Iodine is used today in the form of an iodophor, in which the carrier of the iodine is an inert polymer. This type of delivery agent increases the solubility of iodine by means of a sustained-release reservoir of the halogen. When iodophors are diluted, the amount of free iodine in solution increases. Thus, it is very important to follow the directions for use of this microbicidal product, because as the amount of free iodine increases, so does cell toxicity.

A solution of 1% povidone–iodine is the dilution most commonly used for wound care. This dilution is considered by many researchers to be unsuitable for use in wounds because of its cytotoxicity. Mckenna and Lineaweaver found that a 0.001% dilution was not cytotoxic, but remained effective against some strains of bacteria. One clinical study found that absorption from povidone–iodine preparations after topical administration resulted in possible metabolic complications.

Hydrogen peroxide was first used as a disinfectant by an English physician in 1858 and was marketed under the name Sanitas. The 3% solution was popular for use on wounds from about 1920 to 1950. Hydrogen peroxide kills bacteria by decomposing to hydroxy radicals. It is produced by living cells to protect the body from harm caused by bacteria.

Catalase, a cell enzyme, adequately protects cells from damage by regulating steady-state levels of metabolically produced hydrogen peroxide. This defense overwhelms concentrations of hydrogen peroxide used as a disinfectant on human tissues.Today, hydrogen peroxide has been generally abandoned for use in wounds because of its unfavorable results, and it is a better disinfectant on inanimate objects.

Ethyl alcohol (ethanol) has a long history of medical use. In 1903, it was shown that a 60%–70% solution was the most effective at killing bacteria, but no concentration is sporicidal.

Isopropyl alcohol has a slightly greater bactericidal action than does ethyl alcohol. Both alcohols are relatively nontoxic in topical applications, have a cleansing action, and evaporate readily. They are widely used preceding veni­punctures, hypodermic injections, finger sticks, and other procedures that break the intact skin; they are also used as a hand rinse.
But generally, they are not used in open wounds.

Parenteral antibiotics are frequently applied directly to open wounds, even though their efficacy in this regard has not been established.17 The effectiveness of topical antibiotic irrigation has been shown in vitro and in the surgical research literature.

The focus of that research has been on antibiotic irrigation in the OR. Transferring the use of triple antibiotic irrigation from the OR to the care of open wounds has not been therapeutically beneficial. Moreover, the cost of producing topical antibiotic solutions is significant. Also of concern is the development of, and selection for, resistant organisms after the use of antibiotic topical treatments.

In summary, topical treatment of colonized or infected open wounds is not novel, and several agents have been used over the years. Saline, the most commonly used solution, has no microbicidal activity and has been shown to significantly increase bacterial counts. But the other topical agents (acetic acid, hypochlorite, iodine, hydrogen peroxide, and ethyl or isopropyl alcohol) tend to be toxic to healing tissues or ineffective in reducing bacterial counts. Parenteral antimicrobials have no established therapeutic benefit in the treatment of open wounds, and there is grave concern that their topical use is leading to the emergence of resistant organisms.

Preferred Antiseptic

A topical antiseptic used on open wounds should be nontoxic to healing tissues, should be indiscriminately microbicidal, should promote wound healing, and should not facilitate microbial resistance in the concentrations commonly used in health care settings. The antiseptic introduced for use on open wounds in 1995 in our institution has all of these attributes. It contains 3% p-chloro-m-xylenol and 3% phosholipid PTC as the active ingredients. The formulation, generically called PCMX-PL, is supplied commercially.

PCMX-PL exhibits broad activity against bacteria and fungi. Its mode of action is generalized cell-wall disruption and enzyme inactivation. A 30-second exposure to PCMX-PL results in a 6-log reduction (99.9%) of methicillin-sensitive and methicillin-resistant S. aureus (MRSA) and E. coli.

Our experience with PCMX-PL since 1995 shows that it is associated with markedly improved outcomes for patients with complex, infected open wounds. The impetus to begin using it in our institution was a report from Everett et al in 1994 that showed a 59% first-year survival rate for pancreas-transplant recipients with open, deep infections. Since we began using it, we have noticed a significant improvement in overall survival for our own pancreas-transplant recipients with open, deep, complex infections.

Caring for Surgical Wounds

Our antimicrobial wound-care procedure was developed by the University of Minnesota Department of Surgery’s Surgical Infectious Disease Service, along with infection-control and wound-care professionals from the University of Minnesota Medical Center, Fairview. It was written to accommodate all types of open wounds, from the simple to the complex. Instituted in 2000, it is used widely within our hospital and for outpatients.

The likelihood that a surgical wound will become infected is determined by three factors:

• the inoculum size and the type of contaminating microorganisms;
• the host’s defenses; and
• the extent of wounding (including the amount of time in the OR).

It has been well-established that the risk of wound infection increases with high microbial titers. Wounds contaminated with more than 100,000 microbes per gram of tissue frequently become infected, as shown in experimental and clinical trials. By using PCMX-PL on open wounds that require a surgical procedure, we decrease the inoculum size of the colonizing or infecting microorganisms and decrease the risk of infection.

Multiple environmental studies have shown that microorganisms that colonize or infect an open wound can be cultured from all areas of the patient’s room and from the hands and clothing of health care workers. When hospitalized patients’ wounds become colonized with multidrug-resistant bacteria, such as MRSA, 11%–38% of them will become infected.

Patients infected with multidrug-resistant bacteria have significantly increased morbidity and mortality.Therefore, it is beneficial to attain a significant log reduction of bacteria colonizing or infecting an open wound by using a topical antiseptic such as PCMX-PL. Doing so will lower the risk of bacterial contamination on the patients’ skin and in the hospital environment, and it will prevent the spread of microorganisms from colonized open wounds.

The use of antiseptics becomes increasingly important as reports of multidrug-resistant microorganisms in hospital environments and the community become more prevalent. Our institution’s antimicrobial-resistant bacteria rates compare favorably to those reported by the National Nosocomial Surveillance System.

The use of topical antiseptics, including PCMX-PL, as an adjunct treatment of open wounds plays an important role in preventing the spread of multidrug-resistant microorganisms. Their use is an important addition to the CDC’s campaign to prevent antimicrobial resistance.

Catherine L. Statz, RN, BSN, MPH