The Overuse of Antibiotics

One of the Three Most Serious Health Risks of the 21st Century
By RALPH NADER

Reading a recent issue of Public Citizen's excellent Health Letter titled "Know When Antibiotics Work," I recalled the recent tragic loss of a healthy history professor who was rushed to a fine urban hospital, with a leading infectious disease specialist by his side. No antibiotics could treat his mysterious "superbug." He died in 36 hours.

Wrongful or overuse of antibiotics has a perverse effect—causing the kinds of bacteria that these drugs can no longer destroy. The World Health Organization has cited antibiotic resistance as one of the three most serious public health threats of the 21st century.

The Centers for Disease Control and Prevention (CDC) notes that just in hospitals, where between 5 and 10 percent of all patients develop an infection, about 90,000 of these patients die each year as a result of their infection. This toll is up from 13,300 patient deaths in 1992. Some percentage of these people have problems because of antibiotic resistance.

No matter how many national and global public health organizations warn about this silent, deadly epidemic, no matter how many official recognitions and definition of the problems and demands for local and international action, the fatality toll and the economic costs keep growing.

As Dr. Sidney Wolfe, editor of the Health Letter says: "We've known about this problem for and the needed solutions for well over 30 years but almost nothing is being done about it!" The drug companies keep pushing these drugs while investing too little in truly new antibiotics that can overtake resistant bacteria. Too many doctors still prescribe antibiotics for viral infections that should not be treated with antibiotics. They don't work on viruses. These include, says Dr. Wolfe, "colds, flu—in the absence of bacterial complications, most coughs and bronchitis, sore throats (except those resulting from strep throat) and some ear infections.

Doctors say that patients demand antibiotics—its part of the culture. But doctors should be there to inform patients in those instances when antibiotics are inappropriate.

The CDC states that "many infectious diseases are increasingly difficult to treat because of antimicrobial-resistant organisms, including HIV infection, staphylococcal infection, tuberculosis, influenza, gonorrhea, candida infection and malaria."

Dr. Wolfe writes that "drug resistant infections also spread in the community at large. Examples include drug-resistant pneumonias, sexually transmitted diseases (STDs) and skin and soft tissue infections."

Let us pause for a puzzling question. How many elected representatives, whose chore they say is America's safety, spend any time on this devastating taking of lives because of preventable antibiotic resistant infections, compared to the daily focus on terrorism and the trillions of dollars spent on arms, surveillance, searching of tens of millions of Americans (at airports, for example) and sending soldiers all over the world to kill and be killed?

"Smart use of antibiotics," says Dr. Wolfe, "is the key to controlling the spread of resistance. Too many types of bacteria have become stronger and less responsive to antibiotic treatment when it is really needed. These antibiotic resistant bacteria can quickly spread to family members, schoolmates and co-workers—threatening the community with a new strain of infectious diseases that is more difficult to cure and more expensive to treat."

The veterinary medical community as well is showing a growing concern of too many antibiotics in domesticated animals which enter the human food supply.

"Repeated and improper uses of antibiotics are primary causes of the increase in drug-resistant bacteria," says the Public Citizen Health Letter, adding that bacteria that survive an antibiotic change so as to "neutralize or escape the effect of the antibiotic" then multiply rapidly.

There are lots to be done by many participants in the production, prescription, sale and use of these drugs. You can start by questioning your doctor and not buying soaps, handwipes and cleaning agents whose vendors lure you with the label "antibacterial."

For more about what you can do, visit citizen.org/hrg.

Drug-resistant super bacteria found in three US states and Canada

By The Associated Press - Monday, September 13th, 2010

An infectious-disease nightmare is unfolding: Bacteria that have been made resistant to nearly all antibiotics by an alarming new gene have sickened people in three states and are popping up all over the world, health officials reported Monday.

The U.S. cases and two others in Canada all involve people who had recently received medical care in India, where the problem is widespread. A British medical journal revealed the risk last month in an article describing dozens of cases in Britain in people who had gone to India for medical procedures.

How many deaths the gene may have caused is unknown; there is no central tracking of such cases. So far, the gene has mostly been found in bacteria that cause gut or urinary infections.

Scientists have long feared this — a very adaptable gene that hitches onto many types of common germs and confers broad drug resistance, creating dangerous "superbugs."

"It's a great concern," because drug resistance has been rising and few new antibiotics are in development, said Dr. M. Lindsay Grayson, director of infectious diseases at the University of Melbourne in Australia. "It's just a matter of time" until the gene spreads more widely person-to-person, he said.

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Grayson heads an American Society for Microbiology conference in Boston, which was buzzing with reports of the gene, called NDM-1 and named for New Delhi.

The U.S. cases occurred this year in people from California, Massachusetts and Illinois, said Brandi Limbago, a lab chief at the Centers for Disease Control and Prevention. Three types of bacteria were involved, and three different mechanisms let the gene become part of them.

"We want physicians to look for it," especially in patients who have traveled recently to India or Pakistan, she said.

What can people do?

Don't add to the drug resistance problem, experts say. Don't pressure your doctors for antibiotics if they say they aren't needed, use the ones you are given properly, and try to avoid infections by washing your hands.

The gene is carried by bacteria that can spread hand-to-mouth, which makes good hygiene very important.

It's also why health officials are so concerned about where the threat is coming from, said Dr. Patrice Nordmann, a microbiology professor at South-Paris Medical School. India is an overpopulated country that overuses antibiotics and has widespread diarrheal disease and many people without clean water.

"The ingredients are there" for widespread transmission, he said. "It's going to spread by plane all over the world."

The U.S. patients were not related. The California woman needed hospital care after being in a car accident in India. The Illinois man had pre-existing medical problems and a urinary catheter, and is thought to have contracted an infection with the gene while traveling in India. The case from Massachusetts involved a woman from India who had surgery and chemotherapy for cancer there and then traveled to the U.S.

Lab tests showed their germs were not killed by the types of drugs normally used to treat drug-resistant infections, including "the last-resort class of antibiotics that physicians go to," Limbago said.

She did not know how the three patients were treated, but all survived.

Doctors have tried treating some of these cases with combinations of antibiotics, hoping that will be more effective than individual ones are. Some have resorted to using polymyxins — antibiotics used in the 1950s and '60s that were unpopular because they can harm the kidneys.

The two Canadian cases were treated with a combination of antibiotics, said Dr. Johann Pitout of the University of Calgary in Alberta, Canada. One case was in Alberta, the other in British Columbia.

Both patients had medical emergencies while traveling in India. They developed urinary infections that were discovered to have the resistance gene once they returned home to Canada, Pitout said.

The CDC advises any hospitals that find such cases to put the patient in medical isolation, check the patient's close contacts for possible infection, and look for more infections in the hospital.

Any case "should raise an alarm," Limbago said.

Are you ready for a world without antibiotics?

Antibiotics are a bedrock of modern medicine. But in the very near future, we're going to have to learn to live without them once again. And it's going to get nasty

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• Sarah Boseley
• The Guardian, Thursday 12 August 2010

Streptococcus pyrogens bacteria. Photograph: S Lowry/University of Ulster/Getty Images

Just 65 years ago, David Livermore's paternal grandmother died following an operation to remove her appendix. It didn't go well, but it was not the surgery that killed her. She succumbed to a series of infections that the pre-penicillin world had no drugs to treat. Welcome to the future.

The era of antibiotics is coming to a close. In just a couple of generations, what once appeared to be miracle medicines have been beaten into ineffectiveness by the bacteria they were designed to knock out. Once, scientists hailed the end of infectious diseases. Now, the post-antibiotic apocalypse is within sight.

Hyperbole? Unfortunately not. The highly serious journal Lancet Infectious Diseases yesterday posed the question itself over a paper revealing the rapid spread of multi-drug-resistant bacteria. "Is this the end of antibiotics?" it asked.

Doctors and scientists have not been complacent, but the paper by Professor Tim Walsh and colleagues takes the anxiety to a new level. Last September, Walsh published details of a gene he had discovered, called NDM 1, which passes easily between types of bacteria called enterobacteriaceae such as E. coli and Klebsiella pneumoniae and makes them resistant to almost all of the powerful, last-line group of antibiotics called carbapenems. Yesterday's paper revealed that NDM 1 is widespread in India and has arrived here as a result of global travel and medical tourism for, among other things, transplants, pregnancy care and cosmetic surgery.

"In many ways, this is it," Walsh tells me. "This is potentially the end. There are no antibiotics in the pipeline that have activity against NDM 1-producing enterobacteriaceae. We have a bleak window of maybe 10 years, where we are going to have to use the antibiotics we have very wisely, but also grapple with the reality that we have nothing to treat these infections with."

And this is the optimistic view – based on the assumption that drug companies can and will get moving on discovering new antibiotics to throw at the bacterial enemy. Since the 1990s, when pharma found itself twisting and turning down blind alleys, it has not shown a great deal of enthusiasm for difficult antibiotic research. And besides, because, unlike with heart medicines, people take the drugs for a week rather than life, and because resistance means the drugs become useless after a while, there is just not much money in it.

Dr Livermore, whose grandmother died for lack of infection-killing drugs in 1945, is director of the antibiotic resistance monitoring and reference laboratory of the Health Protection Agency. Last year, the HPA put out an alert to medical professionals about NDM 1, urging them to report all suspect cases. Livermore is far from sanguine about the future.

"A lot of modern medicine would become impossible if we lost our ability to treat infections," he says. He is talking about transplant surgery, for instance, where patients' immune systems have to be suppressed to stop them rejecting a new organ, leaving them prey to infections, and the use of immuno-suppressant cancer drugs.

But it is not just an issue in advanced medicine. Antibiotics are vital to abdominal surgery. "You safeguard the patient from bacteria leaking into the body cavity," he says. "If you lose the ability to treat these infections, far more people would die of peritonitis." Appendix operations would carry the same risk as they did before Fleming discovered penicillin in 1928.

It may not be over yet, he says, but "we are certainly scraping the bottom of the barrel to find antibiotics that are effective against some of the infections caused by bacteria."

Running out is not the only issue, he says. When somebody has a severe infection – say blood poisoning – causing a high fever, a hospital clinician will dispatch blood samples to the lab to find out exactly what he is dealing with. But that takes time. "He will start you on antibiotics because that will kill infection within 48 hours," says Livermore. "So during 48 hours, you are being treated blind. The more resistant your bacteria are, the less likely the antibiotic is going to work."

Studies have shown, he says, that the chances of dying from hospital pneumonia or septicaemia (blood poisoning) are twice as high if the bacteria are drug-resistant, rising in the case of pneumonia from 20-30% to 40-60%.

For a long time now, doctors have known they were in a race to stay a few steps ahead of the rapidly growing resistance of bacterial infections to antibiotics. Ten years ago, the so-called superbug MRSA caused front-page panic. Hospital patients were picking up Staphylococcus aureus infections that were resistant to the hitherto powerful antibiotic methicillin. All-out war, led by the government's former chief medical officer Sir Liam Donaldson, against MRSA and also C. diff (Clostridium difficile) has reduced the threat of what are known as Gram-positive bacteria. Hospital hygiene has been massively stepped up and, in response in part to public anxiety, pharmaceutical companies have put money into finding new antibiotics for those infections.

Chlamydia trachomatis bacteria. Photograph: Eye of Science/Science Photo Library

But it's like putting a finger in a hole in the dam, only to find the water surges out somewhere else. Bacteria are great survivors. The biggest threat now, experts believe, is from multi-drug-resistant Gram-negative bacteria, such as NDM 1-producing enterobacteriaceae and an enzyme called KPC which has spread in the US (and in Israel and Greece) which also gives bacteria resistance to the carbapenems, the most powerful group of antibiotics we (once) had.

"The emergence of antibiotic resistance is the most eloquent example of Darwin's principle of evolution that there ever was," says Livermore. "It is a war of attrition. It is naive to think we can win."

So the game now is to keep bacteria at bay. Hygiene is an obvious weapon. Better cleaning, hand gels and stern warnings to staff and public alike have helped reduce infection rates in hospitals. But Professor Richard James, director of the centre for healthcare associated infections at the University of Nottingham, warns that bugs don't stay in hospitals (indeed, the NDM 1- producing bacteria appear to be widespread in the community in India, passed on through contaminated water, in which people bathe, wash clothes and also defecate).

"The worry is once these organisms are out in the community," says James. "There probably is some need for public education about infection and, for instance, kitchen hygiene when you are cooking. People of my generation were taught a lot about washing your hands before every meal. It was automatic that it was done. A lot of that has gone." There are some innovative ideas about, he says, on ways of teaching children in school to wash their hands – in the hope that they will then go home and pester their parents to do the same.

Beyond that, there is a real need to conserve those antibiotics we have. "To me, it has many parallels with the problems of energy in economies around the world," he says. Carbon trading was dreamed up to try to conserve oil and reduce its pollutant effects. There have now been a couple of interesting papers suggesting a Pigouvian tax – which he defines as one levied on an agent causing an environmental problem as an incentive to mitigate that problem – for antibiotics.

Like oil, he points out, antibiotic usefulness is finite. And the cost of drug resistance is not reflected in the price of the drug. "If you consider antibiotic sensitivity as a resource like oil, you want to maintain that by introducing a tax," he says. It would be worldwide and the proceeds could fund new drug development.

But should you tax life-saving drugs, especially in poor countries? "If you don't do anything, there won't be any antibiotics anyway," says James starkly. "At least it is a suggestion of something that could be done."

If anybody had doubted it for a moment, Walsh's paper shows that neither the UK nor any other country can pull up the drawbridge. "This report shows that the battle to control the emergence of antibiotic-resistant superbugs through appropriate use of antibiotics must be fought at an international level," says Kevin Kerr, consultant microbiologist at Harrogate district hospital. "It illustrates the importance of considering health issues as a world issue – how antibiotics are prescribed and controlled in one part of the world can very rapidly have consequences elsewhere," says Christopher Thomas, professor of molecular genetics at the University of Birmingham.

"Frankly, pharmaceutical companies as well as governments and the European Commission need to really get their act together," says Walsh, who has been urging co-ordinated efforts across the world to put in place good surveillance systems to find out what resistance is developing and where, and then look for interventions. He had Columbia, Mexico, Thailand and India all willingly on board for one surveillance scheme, but the European Commission would not fund it. "What we need is for somebody to give us something like €3m [£2.5m] a year. It's not a lot of money."

The fact is that many people have still got their heads in the sand. But soon we will start seeing patients in NHS hospitals whose infections won't clear up. In the battle for survival of the fittest between human beings and bacteria, just now it looks as though the best we are going to get is a draw – if we are lucky.

After antibiotics: what happens when the drugs don't work

• Transplant surgery becomes virtually impossible. Organ recipients have to take immune-suppressing drugs for life to stop rejection of a new heart or kidney. Their immune systems cannot fight off life-threatening infections without antibiotics.

• Removing a burst appendix becomes a dangerous operation once again. Patients are routinely given antibiotics after surgery to prevent the wound becoming infected by bacteria. If bacteria get into the bloodstream, they can cause life-threatening septicaemia.

• Pneumonia becomes once more "the old man's friend". Antibiotics have stopped it being the mass-killer it once was, particularly among the old and frail, who would lapse into unconsciousness and often slip away in their sleep. Other diseases of old age, such as cancer, have taken over.

• Gonorrhea becomes hard to treat. Resistant strains are already on the rise. Without treatment, the sexually transmitted disease causes pelvic inflammatory disease, infertility and ectopic pregnancies.

• Tuberculosis becomes incurable – first we had TB, then multi-drug-resistant TB (MDR-TB) and now there is XDR-TB (extremely drug resistant TB). TB requires very long courses (six months or more) of antibiotics. The very human tendency to stop taking or forget to take the drugs has contributed to the spread of resistance.