Tuesday, November 10, 2015

Health Care in America - The Sword of Damocles - Antibiotics


The Broken American Health Care System

Classics scholar Daniel Mendelson on the metaphor of the Sword of Damocles from the ancient Greek parable by Cicero:

"The real point of the story is very clearly a moral parable. It's not just, oh, something terrible is going to happen, but it's about realizing that what looks like an enviable life, a life of wealth, a life of power, a life of luxury is, in fact, fraught with anxiety, terror and possibly death."

What are Antibiotics?

Bacteria are everywhere, including on the skin and in the digestive system of humans. While bacteria are critical to normal bodily functions, some types can cause illness. In humans, antibiotics are used to treat health conditions caused by bacteria, including ear and skin infections, food poisoning, pneumonia, meningitis and other serious illnesses. Antibiotics are also used to treat or prevent infections that can complicate critical medical procedures including surgery, cancer therapy, and transplants.

Antibiotics belong to a category of drugs called "antimicrobials," and include penicillin, tetracycline, amoxicillin and many other formulations that can kill or inhibit the growth of bacteria without causing significant harm to the patient. Antibiotics were initially derived from natural compounds. Many organisms, including various types of fungi, produce substances that destroy bacteria and prevent infection.

Penicillin, perhaps the most famous of all antibiotic drugs, is derived from a common fungus called Penicillium. Many other fungi also produce antibiotic substances, which are now widely used to control diseases in human and animal populations. The discovery of antibiotics revolutionized health care worldwide.

Today, there are hundreds of antibiotics in use, most of which are synthetically produced.

What are Antibiotic-Resistant Bacteria?

Just as immunization helps the human body fight disease by exposing the body to small amounts of a virus or bacteria, when bacteria are continually exposed to small amounts of antibiotics they can develop immunity to them. Over time this leads to the development of new, stronger strains of bacteria, with the antibiotic immunity passed on to subsequent generations.

It's a case of "survival of the fittest," with the strongest bacteria, that are least susceptible to a specific antibiotic, living on, adapting and multiplying. These are called "resistant bacteria" because they have adapted to the point where antibiotics can no longer kill them. As a result, some antibiotics have lost their effectiveness against specific infectious diseases. For example, certain strains of tuberculosis are now resistant to antibiotics that were previously effective in fighting them.

Another example is staphylococcus aureus, a bacteria that is the most common cause of staph infections, and that can cause pneumonia, meningitis, toxic shock, skin abscesses, heart valve infections and other serious and deadly medical conditions. In the United States, almost every strain of s. aureus is now resistant to the antibiotics oxacillin, penicillin and amoxicillin, and strains of the disease have begun developing resistance to newer drugs like methicillin and vancomycin. The threat of prolonged illness or death from an s. aureus infection has increased as it has become more resistant and fewer drugs are able to effectively control or eliminate it.

Antibiotic resistance has been accelerated by extreme overuse of antibiotics in humans and animals. Over-prescribing antibiotics for viral-caused conditions like the flu or common cold, against which antibiotics are useless, contributes to antibiotic resistance. As the American Academy of Pediatrics notes, "When antibiotics aren't used the right way, they can do more harm than good."

For example, children who are given antibiotics for ear infections are more likely to get another ear infection, sooner, than those who are not prescribed these drugs. In recent years the academy has urged its members to drastically reduce the antibiotic prescriptions they write.

Penicillin: the first miracle drug

Many of you are here only because penicillin saved your life, or the life of one of your parents or grandparents. Penicillin's ability to cure people of many once-fatal bacterial infections has saved so many lives that it is easy to understand why it was once called a "miracle drug".

Antibiotics are chemicals, effective at very low concentrations, created as part of the life process of one organism, which can kill or stop the growth of a disease-causing microbe--a germ.

In 1929, Alexander Fleming, a doctor and researcher at St. Mary's Hospital in London, England, published a paper on a chemical he called "penicillin", which he had isolated from from a mold, Penicillium notatum. Penicillin, Fleming wrote, had prevented the growth of a neighboring colony of germs in the same petri dish.

Dr. Fleming was never able to purify his samples of penicillin, but he became the first person to publish the news of its germ-killing power. Howard Florey, Ernst Chain and Norman Heatley expanded on Fleming's work in 1938, at Oxford University. They and their staff developed methods for growing, extracting and purifying enough penicillin to prove its value as a drug.

World War II (1939-1945) had begun by the time their research was showing results. The main research and production was moved to the United States in 1941, to protect it from the bombs pounding England. Work began on how to grow the mold efficiently to make penicillin in the large quantities that would be needed for thousands of soldiers.

As the destruction of the war grew, so did interest in penicillin in laboratories, universities and drug companies on both sides of the Atlantic. The scientists knew they were in a race against death, because an infection was as likely to kill a wounded soldier as his wound.

Creating the right environment for growth was the first step in producing enough penicillin to be used as a drug. In Oxford, experiments showed that Penicillium notatum grew best in small shallow containers on a broth of nutrients. Penicillium need lots of air. In the United States, it was discovered that huge "deep fermentation" tanks could be used if sterilized air was pumped continually through the tanks.

Production increased even more when corn steep liquor, a thick, sticky by-product of corn processing, was added to the tanks. Corn steep liquor contained concentrated nutrients that increased the yield 12-20 times. Formerly considered a waste material, corn steep liquor became a crucial ingredient in the large-scale production of penicillin.

Scientists were also determined to find another strain of Penicillium that might grow better in the huge deep fermentation tanks. Army pilots sent back soil samples from all over the world to be tested for molds. Residents of Peoria, Illinois, were encouraged to bring moldy household objects to the local U.S. Department of Agriculture laboratory, where penicillin research was being conducted. Laboratory staff members also kept an eye out for promising molds while grocery shopping or cleaning out their refrigerators.

In 1943, laboratory worker Mary Hunt brought in an ordinary supermarket cantaloupe infected with a mold that had "a pretty, golden look." This Penicillium species, Penicillium chrysogenum grew so well in a tank that it more than doubled the amount of penicillin produced.

The deep fermentation method, the use of corn steep liquor and the discovery of P. chrysogenum by Mary Hunt made the commercial production of penicillin possible. Researchers continued to find higher-yielding Penicillium molds, and also produced higher yielding strains by exposing molds to x-rays or ultraviolet light.

Penicillin kills by preventing some bacteria from forming new cell walls. One by one, the bacteria die because they cannot complete the process of division that produces two new "daughter" bacteria from a single "parent" bacterium. The new cell wall that needs to be made to separate the "daughters" is never formed.

Some bacteria are able to resist the action of antibiotic drugs, including penicillin. Antibiotic resistance occurs because not all bacteria of the same species are alike, just as people in your own family are not exactly alike. Eventually, the small differences among the bacteria often mean that some will be able to resist the attack of an antibiotic. If the sick person's own defenses can not kill off these resistant bacteria, they will multiply. This antibiotic-resistant form of a disease can re-infect the patient, or be passed on to another person.

Taking antibiotics for viral illnesses like colds can also cause antibiotic resistant bacteria to develop. Antibiotics have no effect on viruses, but it will kill off harmless and even the beneficial bacteria living in the patient's body. The surviving resistant bacteria, free from competition, will live and multiply and may eventually cause disease.

Patients with bacterial infections, who don't finish their antibiotic prescriptions completely, also allow resistant bacteria to develop. This happens because a small number of semi-resistant bacteria, which needed the full course of antibiotics to kill them, survive. Instead of being a small part of the bacteria causing an infection, the more resistant bacteria take over when sensitive bacteria are killed by the antibiotic.

Today, in the United States, deaths by infectious bacterial diseases are only one-twentieth of what they were in 1900, before any antibiotic chemicals had been discovered. The main causes of death today are what are referred to as "the diseases of old age": heart disease, kidney disease and cancer. We would be shocked to hear of someone dying from an infection that started in a scratch, but, before antibiotics like penicillin, it was common for people to die from such infections.

Humans can slow the creation of antibiotic resistant diseases by understanding the uses and limits of antibiotics. Take all of an antibiotic, and only take them when prescribed by a doctor. Research to develop new antibiotics to treat resistant bacteria continues, but research takes time. Time is running out because the world's biodiversity is decreasing--the source of half of our disease-fighting chemicals.

How antibiotics are used and abused

Perhaps you are wondering about the use -- and abuse -- of antibiotics in general. Let me give you an example. One of the most common diagnoses given at a doctor’s office is the upper respiratory infection (URI). It accounts for up to 70 percent of all antibiotics dispensed (Annals of Internal Medicine. American College of Physicians. American Society of Internal Medicine. March 20, 2001).

However, according to Dr. Carol Kauffman, most URIs are not caused by the bacteria that antibiotics are designed to fight. Rather, Kauffman says, they are caused by fungi. So, unless a secondary, bacterial infection presents itself -- and even then, the rules change -- most URIs do not require the use of antibiotics.

Regarding ear infections, in one study, children administered antibiotics for acute otitis media suffered double the rate of adverse effects compared to children in the study who took placebos (Clinical Evidence. 2000). The difference in outcome for those children in the study who took antibiotics compared to those who do not was almost negligible. Some scientists counter that children who take antibiotics run lower risks of secondary ear infections such as meningitis or mastoiditis (infection of the angular bone located behind your ear).

Of course, the landscape is complicated by noncompliance. The portion of people who take their antibiotics as prescribed has been estimated at anywhere between 8 to 68 percent. So it’s difficult to say just how effective antibiotics actually are.

Antibiotics in use today

Alexander Fleming, by the grace of God, brought us a mixed blessing in 1928 with his accidental discovery of penicillin produced by, of all things, a fungus. Medicine’s interest treating people for exposure to fungi dropped dramatically in succeeding years, until the microbes were only thought important insofar as their ability to produce increasingly diverse varieties of antibiotics.

Antibiotics and the Animal Industry

Industrial farms have been mixing antibiotics into livestock feed since 1946, when studies showed that the drugs cause animals to grow faster and put on weight more efficiently, increasing meat producers' profits. Today antibiotics are routinely fed to livestock, poultry, and fish on industrial farms to promote faster growth and to compensate for the unsanitary conditions in which they are raised.

Modern industrial farms are ideal breeding grounds for germs and disease. Animals live in close confinement, often standing or laying in their own filth, and under constant stress that inhibits their immune systems and makes them more prone to infection. According to the Union of Concerned Scientists, as much as 70 percent of all antibiotics used in the United States is fed to healthy farm animals.

When drug-resistant bacteria develop at industrial livestock facilities, they can reach the human population through food, the environment (i.e., water, soil, and air), or by direct contact with animals (i.e., farmers and farm workers).

Industrial livestock operations produce an enormous amount of concentrated animal waste, over one billion tons annually—that is often laden with antibiotics, as well as antibiotic-resistant bacteria from the animals' intestines. It is estimated that as much as 80 to 90 percent of all antibiotics given to animals are not fully digested and eventually pass through the body and enter the environment, where they can encounter new bacteria and create additional resistant strains.

With huge quantities of manure routinely sprayed onto fields surrounding CAFOs, antibiotic resistant bacteria can leech into surface and ground water, contaminating drinking wells and endangering the health of people living close to large livestock facilities.

Antibiotic Resistance, Public Health and Public Policy

Antibiotic-resistant bacteria is a growing public health crisis because infections from resistant bacteria are increasingly difficult and expensive to treat. As of this writing, the U.S. Congress was considering legislation, staunchly opposed by industrial farm lobbyists, which would ban seven classes of antibiotics from use on factory farms and would restrict the use of other antibiotics. This is a response to the fact that modern industrial livestock operations threaten to increase the prevalence of antibiotic-resistant bacteria.

Thousands of Americans die every year from drug-resistant infections. In addition, the National Academy of Sciences calculates that increased health care costs associated with antibiotic-resistant bacteria exceed $4 billion each year in the United States alone—a figure that reflects the price of pharmaceuticals and longer hospital stays, but does not account for lost workdays, lost productivity or human suffering.

Although everyone is at risk when antibiotics stop working, the threat is greatest for young children, the elderly, and people with weakened immune systems, including cancer patients undergoing chemotherapy, organ transplant patients and, in general, people whose health is compromised in some way.

The following excerpt is from an article by Carol R. Goforth.

The headlines are sensational enough that it wouldn’t be surprising to see them in the most notorious supermarket tabloids. The stories behind the headlines are scary enough that they might be the plot of a horror movie. Unfortunately, it is often the scientific press that is reporting on the spread of antibiotic-resistant bacteria, and the threat to human health and life is very real and growing.

The increase in public awareness about the spread of antibiotic-resistant bacteria has been occasioned by a significant increase in the number of reported cases of human illness associated with antibiotic resistance. Studies show that infectious disease mortality rates have risen nearly 60%, with the Centers for Disease Control (CDC) estimating that more than half of the infection-related deaths involve resistant bacteria.

Dubbed “super-bugs” in the popular press, multi-drug resistant bacteria are becoming more and more common. Newspapers and magazines carry stories of bacterial infections that do not respond to the antibiotics typically prescribed to control them. As one legal commentator observed, “many of the killer diseases of the past such as tuberculosis, typhoid fever, diphtheria, and pneumonia have returned to wreak havoc as bacteria are increasingly resistant to antibiotics.” While antibiotics were once regarded as an unending miracle of modern medicine, we are fast approaching a time when the miracle may come to an end.

While there are doubtless many factors contributing to the spread of multi-resistant bacteria, one factor appears to be the widespread addition of antibiotics to livestock feed. A wide range of antibiotics are currently added, in subtherapeutic amounts, to animal feeds. A growing volume of research suggests that this practice is having devastating and potentially irreversible effects on the viability of antibiotics as agents to effectively treat diseases in human beings, but the legal community appears to be lagging far behind scientific experts in calling for an end to this practice in the United States.

At the current time, there are three primary uses of antibiotics in animal agriculture: therapeutic, prophylactic (to prevent potential infection), and growth promotion (with both of the latter two categories being at subtherapeutic concentrations).

The use of antibiotics to ward off infections and to promote growth in livestock is not new. For more than 40 years many farmers have fed their animals a diet laced with small, subtherapeutic doses of antibiotics.

The discovery that antibiotics could be used for prevention of infection and growth promotion was serendipitous. Veterinarians began administering antibiotics to sick animals in an effort to determine whether the “miracle drugs” that were saving human lives could also help livestock.

These experiments led to the discovery that feeding animals small doses of the drugs not only inhibited diseases but also enhanced growth. This discovery led in turn to an agricultural revolution, with farmers—especially those in very large operations relying increasingly on subtherapeutic doses of antibiotics to keep their livestock healthy and to promote animal growth.

In the past three decades, agricultural use of antibiotics has increased exponentially. One article has estimated that in the past thirty years, farmers have increased their use of penicillin-type antibiotics in farm animals by 600% and their use of tetracycline by 1500%. Recent statistical research continues to show an increasing reliance on the routine use of antibiotics for pigs and cattle. Larger operations also continue to be more likely to use antibiotics, and many rely on additives for periods of time in excess of ninety days.

Part of the increase in antibiotic use is attributable to the declining effectiveness of the drugs as growth promoters. Over time, the amount of antibiotics needed to promote growth in farm animals has increased significantly. Some sources have suggested that “roughly 10 to 20 times the amount used four decades ago were required to produce the same level of growth in the 1990s.”

Moreover, even at concentrations approaching therapeutic levels, “the benefits of growth promotion are less now than those reported several decades ago.”

Antibiotic use and abuse

There has been an astonishing increase in the use of antibiotics in spite of the dangers of abuse.  In 1954 2 million pounds of antibodies were produced inn America, while today estimates of production exceed 50 million pounds.

Approximately 16 million pounds are used on humans, the remaining 34 million pounds are used on livestock in our food supply, most used as a food supplement.

Included in the list of antibiotics used as food additives in American agriculture are a number of drugs that are either themselves used as drug therapies for human patients or are closely related to such drugs. Amoxicillin, ampicillin, erythromycin, neomycin, penicillin, and tetracycline are all used to treat human illness as well as being used in animal agriculture.

US General Accounting Office Report - GAO-11-406

July 1, 2011

Infections that were once treatable have become more difficult to treat because of antibiotic resistance. Resistance occurs naturally but is accelerated by inappropriate antibiotic use in people, among other things.

Questions have been raised about whether agencies such as the Department of Health and Human Services (HHS) have adequately assessed the effects of antibiotic use and disposal on resistance in humans.

GAO was asked to (1) describe federal efforts to quantify the amount of antibiotics produced, (2) evaluate HHS's monitoring of antibiotic use and efforts to promote appropriate use, (3) examine HHS's monitoring of antibiotic-resistant infections, and (4) describe federal efforts to monitor antibiotic disposal and antibiotics in the environment, and describe research on antibiotics in the development of resistance in the environment.

GAO reviewed documents and interviewed officials, conducted a literature review, and analyzed antibiotic sales data.

Federal agencies do not routinely quantify the amount of antibiotics that are produced in the United States for human use. However, sales data can be used as an estimate of production, and these show that over 7 million pounds of antibiotics were sold for human use in 2009.

Most of the antibiotics that were sold have common characteristics, such as belonging to the same five antibiotic classes. The class of penicillins was the largest group of antibiotics sold for human use in 2009, representing about 45 percent of antibiotics sold. HHS performs limited monitoring of antibiotic use in humans and has implemented efforts to promote their appropriate use, but gaps in data on use will remain despite efforts to improve monitoring.

GAO did not address the millions of pounds of use on livestock including beef, pigs, fish and chicken nor the implications of transferring drug resistant bacteria from animals to humans since 1946.  Nor did it address the huge discrepancies in the amount of antibiotics produced by pharmaceutical companies.

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