Resistant Bacteria

Antibiotics Prove Powerless as Super-Germs Spread

Antibiotics were once the wonder drug. Now, however, an increasing number of highly resistant -- and deadly -- bacteria are spreading around the world. The killer bugs often originate in factory farms, where animals are treated whether they are sick or not. By SPIEGEL Staff

der Spiegel,
27 January, 2012

The pathogens thrive in warm, moist environments. They feel comfortable in people's armpits, in the genital area and in the nasal mucous membranes. Their hunting grounds are in the locker rooms of schools and universities, as well as in the communal showers of prisons and health clubs.

The bacteria are transmitted via the skin, through towels, clothing or direct body contact. All it takes is a small abrasion to provide them with access to a victim's bloodstream. Festering pustules develop at the infection site, at which point the pathogens are also capable of corroding the lungs. If doctors wait too long, patients can die very quickly.

This is precisely what happened to Ashton Bonds, a 17-year-old student at Staunton River High School in Bedford County, in the US state of Virginia. Ashton spent a week fighting for his life -- and lost. This is probably what also happened to Omar Rivera, a 12-year-old in New York, who doctors sent home because they thought he was exhibiting allergy symptoms. He died that same night.

The same thing almost happened at a high school in the town of Belen, New Mexico. Less than two weeks ago, a cheerleader at the school was hospitalized after complaining about an abscess. Twelve other female students had been afflicted with suspicious rashes. All the students tested positive for a bacterium that the US media has dubbed the "superbug."

The school administration in Belen believes that the bacterium was spread on mats in the school's fitness and wrestling rooms. The facility was thoroughly disinfected 40 times, and yet the fear remains.

Fears of a Pandemic

Microbiologists refer to this bacterium as community-acquired methicillin-resistant Staphylococcus aureus, or ca-MRSA. The terrifying thing about it is its resistance to almost all common antibiotics, which complicates treatment. And, in contrast to the highly drug-resistant hospital-acquired MRSA (ha-MRSA) strains, which primarily affect the elderly and people in hospitals and nursing homes, ca-MRSA affects healthy young people. The bacterium has become a serious health threat in the United States. Doctors have already discovered it in Germany, although no deaths have been attributed to it yet in the country.

The two bacteria, ha-MRSA and ca-MRSA, are only two strains from an entire arsenal of pathogens that are now resistant to almost all available antibiotics. Less than a century after the discovery of penicillin, one of the most powerful miracle weapons ever produced by modern medicine threatens to become ineffective.

The British medical journal The Lancet warns that the drug-resistant bacteria could spark a "pandemic." And, in Germany, the dangerous pathogens are no longer only feared "hospital bugs" found in intensive care units (ICUs). Instead, they have become ubiquitous.

About two weeks ago, consumers were alarmed by the results of an analysis of chicken meat by the environmentalist group Friends of the Earth Germany (BUND), which found multidrug-resistant bacteria on more than half of the chicken parts purchased in supermarkets.

The dangerous bacteria have even been detected on one of Germany's high-speed ICE trains. Likewise, more than 10 percent of the residents of German retirement homes have been colonized by MRSA bacteria. In their case, every open wound is potentially deadly. The pathogens have also been found on beef, pork and vegetables.

Another alarming finding is that about 3 to 5 percent of the population carries so-called ESBL-forming bacteria in the intestine without knowing it. Even modern antibiotics are completely ineffective against these highly resistant bacteria.

Diminishing Defenses

When the neonatal ICU at a hospital in the northern German city of Bremen was infested with an ESBL-forming bacterium last fall, three prematurely born babies died.

Infestation with multidrug-resistant bacteria is normally harmless to healthy individuals because their immune systems can keep the pathogens under control. Problems arise when an individual becomes seriously ill.

"Take, for example, a person who is having surgery and requires artificial respiration and receives a venous or urinary catheter," explains Petra Gastmeier, director of the Institute of Hygiene and Environmental Medicine at Berlin's Charité Hospital. "In such a case, the resistant intestinal bacteria can enter the lungs, the bloodstream and the bladder."

This results in urinary tract infections, pneumonia or sepsis, which are increasingly only treatable with so-called reserve antibiotics, that is, drugs for emergencies that should only be administered when common antibiotics are no longer effective.

The Spread of Killer Bugs

Recently, an even greater threat has arisen. With the spread of ESBL-forming bacteria, reserve antibiotics have to be used more and more frequently, thereby allowing new resistances to develop. In fact, there are already some pathogens that not even the drugs of last resort in the medical arsenal can combat.

In India, where poor hygiene and the availability of over-the-counter antibiotics encourage the development of resistance, an estimated 100 to 200 million people are reportedly already carriers of these virtually unbeatable killer bacteria. There is only one antibiotic left -- a drug that is normally not even used anymore owing to its potentially fatal side effects -- that is still effective against these killer bacteria. In serious cases, people who become infected with these types of pathogens die of urinary tract infections, wound infections or pneumonia.

The killer bugs have also reached England, presumably through medical tourists who traveled to India for cosmetic surgery, and they have reportedly already infected several hundred people. A few cases have also turned up in Germany.

Israel even experienced a nationwide outbreak a few years ago. Within a few months, about 1,300 people were afflicted by an extremely dangerous bacterium that killed 40 percent of infected patients. Even today, the same bacterium still sickens some 300 people a year.

Part 2: The Post Antibiotic Era

This rapid spread has caused many to wonder whether more and more people in Germany will soon die of infectious diseases that were supposedly treatable, as happened in centuries past. Unfortunately, there are many indications that this might ultimately be the case.

"We are moving toward a post-antibiotic era," predicts Yehuda Carmeli of the Tel Aviv Sourasky Medical Center. "But it won't happen on one day or at the same time in every part of the world. And that's the tragedy, because this means that it is not perceived as a serious problem."

The World Health Organization (WHO) recently warned against an impending medical catastrophe. And, in The Lancet, leading healthcare experts published an urgent appeal: "We have watched too passively as the treasury of drugs that has served us well has been stripped of its value. We urge our colleagues worldwide to take responsibility for the protection of this precious resource. There is no longer time for silence and complacency."

In fact, the carelessness with which doctors and farmers are jeopardizing the effectiveness of one of the most important groups of drugs borders on lunacy. Some 900 metric tons of antibiotics are administered to livestock each year in Germany alone. Instead of treating only those animals that are truly sick, farmers routinely feed the medications to all of their animals. 

Likewise, some 300 metric tons of antibiotics are used to treat humans each year, far too often for those merely suffering from a common cold.

A Foe We Helped Become More Flexible

This large-scale use inevitably leads to the spread of resistant bugs. Indeed, antibiotics offer ideal growth conditions to individual bacteria that have naturally become resistant through a small change in their genetic makeup. Simply put, they benefit from the fact that the antibiotics still kill off their competitors, the non-resistant bacteria.

In many cases, a genetic mutation isn't even necessary to allow a resistant bacterium to develop. Bacteria can incorporate bits of genetic material from other pathogens. For example, for millions of years, the gene for ESBL resistance lay dormant in the ground, where it was part of a complicated ecosystem of bacteria, penicillin-producing fungi and plant roots. Again and again, the gene was incorporated by human intestinal bacteria -- as useless ballast. It was only the large-scale use of antibiotics that provided the ESBL-forming bacteria with the opportunity to proliferate.

Recent studies show that quantities of antibiotics much smaller than previously thought can lead to the development of resistance. In retrospect, the uncontrolled dispensing of antibiotics has proven to be a huge mistake. "In the last 30 years, we have contaminated our entire environment with antibiotics and resistant bacteria," says Jan Kluytmans, a microbiologist at Amphia Hospital, in the southern Dutch city of Breda. "The question is whether this is even reversible anymore. Perhaps we can prevent only the worst things from happening now."

Shocking Levels of Antibiotic Abuse on Farms

Since a large share of resistant bacteria come from barns, it will be critical to drastically reduce the use of antibiotics in agriculture. Remarkably often, farmers, feedlot operators and veterinarians are themselves carriers of multidrug-resistant bacteria. Kluytmans has even demonstrated that the pathogens found in humans are very often genetically identical with the bacteria detected on meat

.

It's virtually impossible to become infected by eating such meat, at least as long as it's well-cooked. The risk arises when raw meat comes into contact with small wounds. What's more, even vegetable crops can become contaminated when liquid manure is spread onto fields.

The exhaust gases emitted by giant feedlots for pigs and chickens could also pose a danger greater than previously thought. These meat factories blow bacteria, viruses and fungi into the air. The government of the western German state of North Rhine-Westphalia has commissioned a study to determine whether feedlots are discharging multidrug-resistant bacteria, thereby endangering people in the surrounding areas.

Last year, North Rhine-Westphalia was also the first German state to systematically investigate the use of antibiotics in chicken farms. The horrifying conclusion was that more than 96 percent of all animals had received these drugs -- sometimes up to eight different agents -- in their short lives of only a few weeks. "That was the proof that the exception -- namely, treating disease -- had become the rule," says Johannes Remmel, a Green Party member and the state's consumer protection minister.

Abysmal Feedlot Conditions

As the results of the investigation suggest, factory farming is to blame. The bigger an operation, the more antibiotics are administered to individual animals. Investigators also noted that the duration of antibiotic use was usually very short -- shorter than specified in the licensing requirements. This saves money, but it also promotes the formation of resistance.

The fact that livestock farmers mix antibiotics into feed has to do with production conditions in feedlots:

1.To produce veal, animals from different sources that are too weak for milk and beef production -- and likewise more susceptible to infectious diseases -- are often jammed into enclosures.

2. Pigs are usually kept in very small spaces, making them very aggressive and causing them to fight. Their wounds have to be treated with antibiotics.

3. In the past, it took 80 days until a chicken was ready for slaughter. Today it's only 37 days. Chicken farmers have a profit margin of only a few cents per animal. To minimize losses through disease, poultry producers and their veterinarian helpers use antibiotics as a preventive tool.

However, factory farming is also possible without the uncontrolled use of antibiotics. Dairy cows, for example, are usually not given these drugs since antibiotics would interfere with the production of cheese and yogurt. Nevertheless, there are still plenty of inexpensive milk products on supermarket shelves.

"In the Netherlands," says Kluytmans, "the use of antibiotics in feedlots was even reduced by about 30 percent within two years -- partly as a result of stricter regulations for veterinarians. That's more than we administer to humans." Unfortunately, he adds, the use of antibiotics in feedlots is practically a matter of religious belief.

Efforts to Combat Antibiotics Abuse

In early January, Ilse Aigner, Germany's minister of food, agriculture and consumer protection, unveiled a package of measures aimed at curbing the use of antibiotics in farm animals. The measures include stricter controls that would make it more difficult to add antibiotics urgently needed in human medicine to animal feed. Germany's federal government is also considering suspending veterinarians' right to dispense medicine. In contrast to doctors practicing medicine on humans, who prescribe drugs to be purchased at pharmacies, veterinarians can even directly sell drugs to farmers and feedlot owners, which means they stand to profit handsomely from the large-scale use of antibiotics.

However, Remmel, the consumer protection minister of North Rhine-Westphalia, believes that Aigner's proposals are "deceptively packaged," and he is calling for exact specifications on the amounts of antibiotics that can be used.

Similarly, there is also little control over the use of antibiotics in human medicine. In Germany, in particular, doctors prescribe antibiotics as they see fit, whereas in the Netherlands doctors must first consult with a microbiologist.

"Just as in pain therapy, there really ought to be experts for treatment with antibiotics," says Gastmeier, the director of the Institute of Hygiene and Environmental Medicine at Berlin's Charité Hospital "But young doctors, in particular, are often relatively uninformed." Indeed, in medical school, they learn very little about the proper use of antibiotics.

Little Research into New Antibiotics

Still, even more responsible prescribing practices will hardly be able to stop the advance of resistant bacteria in the long term. What's more, no new antibiotics can be seen on the horizon. Only four pharmaceutical companies worldwide are still working on developing new agents.

"Antibiotics have a serious problem," says Wolfgang Wohlleben of the Institute of Microbiology at the University of Tübingen, in southwestern Germany: "They actually work." Indeed, the drugs can get the better of an infection within a few hours or days, and then they are no longer needed. By contrast, patients taking drugs to fight high blood pressure or diabetes often have to take them for the rest of their lives -- which translates into steady, reliable profits for pharmaceutical companies.

Yet another factor making antibiotic-related R&D unattractive is the fact that doctors can only prescribe a new antibiotic in the most extreme of emergencies lest it lose its efficacy within a short amount of time.

Given these circumstances, major pharmaceutical companies stopped searching for new antibiotics years ago. Nowadays, only small start-ups or university-based researchers are interested in the field.

Abandoned by Big Pharma

In reality, the search for new drugs should be getting easier rather than more difficult. In the 1990s, the large pharmaceutical companies spent several million euros searching for weaknesses in the genetic makeup of bacteria. But although the researchers were actually successful, the subsequently developed drugs never made the final leap into clinical use.

"In the end, the risks of antibiotic research were simply too great for companies," says pharmacist Julia Bandow, who went into academia to continue studying antibiotics after working for the US-based pharmaceutical giant Pfizer for six years.

But without the large pharmaceutical companies, there can be little hope of progress. After all, testing a drug in human subjects takes years and costs millions. And, as Bandow says of her fellow academics, "We can't do it alone."

If pharmaceutical companies refuse to invest in the necessary studies, it's critical for the government to step in. At the least, politicians could make the development of antibiotics more attractive, for example, by extending the time before patents expire so as to allow companies to earn returns on their investments for longer. But, so far, these are all nothing but ideas.

"At some point in the coming years," says microbiologist Kluytmans, "there will be a disaster involving resistant pathogens with many casualties. Only then will something change."