“Human resistance to antibiotics could bring ‘the end of modern medicine as we know it’,” according to The Daily Telegraph. The newspaper says that we are facing an antibiotic crisis that could make routine operations impossible and a scratched knee potentially fatal. Similarly, the Daily Mail’s headline stated that a sore throat could soon become fatal.
The alarming headlines follow a new report by the World Health Organization (WHO , which set out ways to fight the growing problem of antimicrobial resistance (AMR . AMR occurs when infectious organisms, such as bacteria and viruses, adapt to treatments and become resistant to them. The publication specifically addressed the long-known problem of antibiotic resistance, where increasing use of antibiotics can lead to the formation of “superbugs” that resist many of the antibiotic types we currently have. It outlined a variety of measures that are vital for ensuring we can still fight infections in the future and described how other major infectious diseases, such as tuberculosis, HIV, malaria and influenza, could one day become resistant to today’s treatment options.
However, despite the future danger posed by antimicrobial resistance, the situation is not irretrievable. As Dr Margaret Chan, director general of WHO, said: “much can be done. This includes prescribing antibiotics appropriately and only when needed, following treatment correctly, restricting the use of antibiotics in food production to therapeutic purposes and tackling the problem of substandard and counterfeit medicines.” The report also highlighted successful cases where antimicrobial resistance has been tackled, demonstrating that we can safeguard the effectiveness of important antimicrobial medicines with dedicated, rational efforts.
Where has the news come from?
WHO has just published a new report (“The evolving threat of antimicrobial resistance - Options for action” that sets out a global strategy for fighting antibiotic resistance. It explores how over past decades, bacteria that cause common infections have gradually developed resistance to each new antibiotic developed, and how AMR has evolved to become a worldwide health threat. In particular, the report highlights that there is currently a lack of new antibiotics in development and outlines some of the measures needed to prevent a potential global crisis in healthcare.
This is not the first time WHO has set out such a strategy. In the 2001, WHO published its “Global strategy for containment of antimicrobial resistance”, which laid out a comprehensive list of recommendations for combating AMR. The current report looks at the experiences over the past decade of implementing some of these recommendations, the progress made, and what else should be done to tackle AMR.
What is antimicrobial resistance?
Antimicrobial resistance (AMR occurs when microorganisms, such as bacteria, viruses, fungi or other microbes, develop resistance to the drug that is being used to treat them. This means that the treatment no longer effectively kills or inactivates the microorganism. The term “antimicrobial” is used to describe all drugs that treat infections caused by microorganisms. Antibiotics are effective against bacteria only, antivirals against viruses, and antifungals against fungi.
The case of penicillin illustrates the AMR phenomenon well. When penicillin was first introduced in the 1940s, it revolutionised medicine and was effective against a wide range of staphylococcal and streptococcal bacteria. It was also able to treat infections that had previously been fatal for many people, including throat infections, pneumonia and wound infections. However, with increasing use of antibiotics over the decades, bacteria began to adapt and develop changes in their DNA that meant they were resistant to the actions of the once powerful antibiotic. These bacteria would survive and proliferate, which meant their protective genes would then be passed on to other strains of bacteria. As a result, new and stronger antibiotics had to be created to combat the resistant bacteria.
AMR is driven by many factors, including overuse of antimicrobials for human and animal health and in food production, which can allow microbes to adapt to antimicrobials they are exposed to. Poor infection-control measures, which fail to prevent the spread of infections, also contribute. In particular, the WHO publication reports what it describes as the five most important areas for the control of AMR, as recognised in its 2001 strategy:
- surveillance of antimicrobial use
- rational use in humans
- rational use in animals
- infection prevention and control
- innovations in practice and new antimicrobials
How big is the problem?
As the report describes, AMR makes it difficult and more expensive to treat many common infections, causing delays in effective treatment or, in the worst cases, an inability to provide effective treatment at all. Many patients around the world suffer harm because infections from bacteria, viruses, fungi or other organisms can no longer be treated with the common medicines that would once have treated them effectively.
The report presents some startling facts on major infectious diseases worldwide:
- Malaria: malaria is caused by parasites that are transmitted into the bloodstream by a bite from an infected mosquito. Resistance to antimalarial medicines has been documented for all classes of the drug, which presents a major threat to malaria control. The report describes that a change in national antimalarial treatment policy is recommended when the overall treatment failure rate exceeds 10%. Changes in policy have been necessary in many countries due to the emergence of chloroquine resistance. This means that alternative forms of combination therapy have to be used as first-line treatment.
- Tuberculosis: in 2010, an estimated 290,000 new multidrug-resistant tuberculosis (TB cases were detected among the TB cases notified worldwide, and about one-third of these patients may die annually. Inaccuracies in diagnosis also impede appropriate treatment.
- HIV: resistance rates to anti-HIV drug regimens ranging from 10% to 20% have been reported in Europe and the USA. Second-line treatments are generally effective in patients when the first-line therapy has failed, but can only be started promptly if viral monitoring is routinely available.
- Common bacterial infections: various bacteria can cause infections within the chest, skin and urinary tract bloodstream, for example, and the inability to fight these infections appears to a growing problem in healthcare. Estimates from Europe are that there are 25,000 excess deaths each year due to resistant bacterial hospital infections, and approximately 2.5 million avoidable days in hospital caused by AMR. In addition, the economic burden from additional patient illness and death is estimated to be at least ˆ1.5 billion each year in healthcare costs and productivity losses.
What can be done about AMR?
The five key areas that the report highlights could tackle the problem of AMR are as follows:
Surveillance of antimicrobial use
Tracking antimicrobial use (in particular antibiotic use and looking at the emergence and spread of resistant strains of bacteria is a key tactic in the fight against AMR. This can provide information, insights and tools needed to guide policy and measure how successful changes in prescribing may be. This can happen both locally and globally.
AMR is a global problem but, at present, there appears to be wide variation in the way regions and countries approach AMR surveillance. This means there is a long way to go before it can be carried out worldwide.
Rational use in humans
Antimicrobials can obviously be important or even lifesaving in appropriate situations, but it is just as important to prevent unnecessary use of antimicrobials, which can lead to resistance. Putting this into practice worldwide is said to be difficult, but rationalising antimicrobial use has had a demonstrable impact on AMR in some cases.
Rational use in animals
Antibiotics are said to be used in greater quantities in food production than in the treatment of disease in human patients. Also, some of the same antibiotics or classes are used in animals and in human medicine. This carries the risk of the emergence and spread of resistant bacteria, including those capable of causing infections in both animals and people.
The problems associated with the use of antibiotics in animal husbandry, including in livestock, poultry and fish farming, are reportedly growing worldwide without clear evidence of the need for or benefit from it. There are said to be major differences in the amounts of antimicrobials used per kilogram of meat produced in high-income countries, and actions need to be taken by national and international authorities to control this.
Infection prevention and control in healthcare facilities
The hospital environment favours the emergence and spread of resistant bacteria. The report highlights the importance of infection-control measures to prevent the spread of microbes in general, regardless of whether they are resistant to antimicrobials. Many facilities and countries are reported to have progressed well since 2001, implementing many recommendations on infection control and prevention, although gaps and challenges still remain.
Innovations
Lastly, the report describes how innovative strategies and technologies are needed to address the lack of new antimicrobials being produced. As the report says, while antimicrobials are the mainstay of treatment for infections, diagnostics and vaccines play important complementary roles by promoting rational use of such medicines and preventing infections that would require antimicrobial treatment. So far, new products coming on to the market have not kept pace with the increasing needs for improvements in antimicrobial treatment. However, current challenges to new research developments can be both scientific and financial.
Can these strategies really stop AMR?
While AMR poses a significant threat to health in the future, the situation does not appear to be irretrievable. The WHO report and an accompanying press release highlight some examples of success stories over the past years:
- In Thailand, the "Antibiotic Smart Use" programme is reported to have reduced both the prescribing of antibiotics by prescribers and the demand for them by patients. It demonstrated an 18–46% decrease in antibiotic use, while 97% of targeted patients were reported to have recovered or improved regardless of whether they had taken antibiotics.
- A pharmacy programme in Vietnam reportedly consisted of inspection of prescription-only drugs, education on pharmacy treatment guidelines and group meetings of pharmacy staff. These measures were reported to give significant reduction in antibiotic dispensing for acute respiratory infections.
- In Norway, the introduction of effective vaccines in farmed salmon and trout, together with improved fish health management, was reported to have reduced the annual use of antimicrobials in farmed fish by 98% between 1987 and 2004.
- In 2010, the University of Zambia School of Medicine was reported to have revised its undergraduate medical curriculum. AMR and rational use of medicines were made key new topics to ensure that graduates who enter clinical practice have the right skills and attitudes to be both effective practitioners and take a role in fighting AMR.
How can I help?
There are times when antibiotics are necessary or even vital. However, as patients and consumers, it is important to remember that antibiotics or other antimicrobials are not always needed to treat our illnesses, and we should not expect them in every situation.
For example, the common cold is caused by a virus, which means it does not respond to antibiotics. However, people may expect to be given antibiotics by their doctor when they are affected, even though they offer no direct benefit and could raise the risk of bacteria becoming resistant. Furthermore many common viral and bacterial infections such as coughs, throat and ear infections and stomach upsets, are “self-limiting” in healthy people, which means they will generally get better with no treatment at all.
If, on the other hand, you are prescribed an antimicrobial, it is important to take the full course as directed. Taking only a partial course of an antimicrobial may not kill the organism but may expose it to a low dose of a drug which can then contribute to resistance.
Links To The Headlines
Health chief warns: age of safe medicine is ending. The Independent, March 16 2012
Resistance to antibiotics could bring "the end of modern medicine as we know it", WHO claim. The Daily Telegraph, March 16 2012
Why a sore throat could soon be fatal: Bugs are becoming more resistant to antibiotics, warn health chiefs. Daily Mail, March 16 2012
Links To Science
WHO: The evolving threat of antimicrobial resistance - Options for action. March 16 2012
A young Dr. Charles Armstrong, fresh from fighting the world influenza epidemic that came with the Great War, was ordered by U.S. Surgeon General Rupert Blue to his home state of Ohio on July 1, 1919 to provide assistance to the state health officer.
Armstrong, just 33, returned home from war just six weeks before a county club banquet was held for more than 200 people near Canton, Ohio. Fourteen of those attending the banquet became stricken by botulism poisoning and seven of those victims died.
The coincidence of Armstrong's assignment to help out in Ohio meant he who would go on to worldwide recognition as virologist with his 1934 discovery of the virus he named lymphocytic choriomeningitis (LCM .
For the California olive industry, this meant the botulism outbreak of 1919 was going to be thoroughly and definitely tied around its neck. With a total of 19 botulism deaths in three states -- that were conclusively linked to canned California olives -- made the outbreak one of the deadliest outbreaks in the U.S.
The California olive industry owed it existence to those first olive trees planted in the mission orchards at San Diego, San Jose, Santa Clara and others before the American Revolution. For 20 years, it had been commercially viable, but the 1919 botulism outbreak was an unmitigated disaster. California olives did not recover for more than a decade.
Other U.S. states -- where those mission olive trees would never grow -- were the market for California canned ripe olives and now botulism in a can from California made for a pretty sensational story.
To make matters worse, California olive growers were not helped by the fact that, after 1919, the botulism outbreaks linked to olives did not really end until 1924.
The 1919 outbreak left dead in three states: Ohio (7 , Montana (5 , and Michigan (7 .
It is Ohio that always gets the most attention, however, because of the Armstrong's investigation and the unusual circumstances he found at the country club. He found that at the country club event attended, which was attended by more than 200 people, the botulism was all contained to people who sat at one table, the chef and two waiters.
"The guests who became ill were all members of a party given by Mrs. I.W.G., of Sebring, Ohio, and had been served at a separate table which shall hereafter be designed as the Sebring table," Armstrong wrote. "The two waiters who attended this table and the chef were also affected."
Armstrong reported the banquet menu included: cantaloupe, turkey, turkey stuffing, tomatoes and mayonnaise, crackers, scalloped corn and pimentos, browned potatoes, green olives, celery and pickles, rolls, butter, ice cream cake, water and coffee.
But he found the Sebring table did not get the green olives, celery, and pickles. Instead, Mrs. I.W.G. provided ripe olives, chocolate candy, Newport creams and candied almonds.
In the Dec. 19, 1919 edition of Public Health Reports, Armstrong includes the seating chart for the Sebring table that also includes the location of the three plates of ripe olives. Five of those in proximity to the olive servings died including Mrs. I.W.G.
Botulism also killed the chef and a waiter.
By the time his investigation got underway, six of the cases "had terminated fatally," according to Armstrong. While no illnesses occurred among those at other tables, Armstrong interviewed 15 of those guests and he also conducted a full blown epidemiological study to exclude all the items on the menu.
Of the 14 people who were ill, all ate olives. "When the dead are considered, it is found in a general way that those who died first who ate the most olives," Armstrong said.
Among those who were recovering, he said those who ate the least suffered were less severe cases. Those who survived reported the olives did not taste right. Asked to describe it, they said things like the olives "bit the tongue" and "stuck to the tongue" or just said they were "not fit to eat."
Armstrong found the ripe olives came from a vacuum-sealed jar and concluded, "something had occurred to destroy the vacuum in the jar, for, in opening it, the lid is said to have come off easily without having been punctured and without the use of instruments." The lid was discarded, but the recovered glass jar "was not cracked or defective in any way."
One of the waiters did not think the olives tasted right, and near the end of the banquet, he took them to the chef to get another opinion. The chef ate two, unwashed, and was among those who died. One of the two waiters for the Sebring table and a guest, both of whom survived credited the amount of whiskey they drank that evening as possibility saving their lives.
Pushing on, the investigation found the source of the contaminated olives to be the Ehmann Olive Company, formed in 1898 by Mrs. Freda Ehmann. She started California's commercial olive industry and credited with establishing the modern California ripe olive industry.
She arrived in California as a widow in the 1890's when olive planting was peaking. She lost her first investment in a ranch called Olive Hill Grove and then turned her attention to perfecting a recipe for pickled olives and selling it to grocers.
By 1900, Ehmann Olive Company was running 90 vats at a large processing plant in Oroville, CA.
Dr. Judith Taylor, who wrote the book "The Olive in California," interviewed Freda Ehmann's grand-daughter who said her grandmother never could come to terms about the company's role in the 1919 outbreak.
USDA's Bureau of Chemistry did a study of Ehmann's glass and metal containers in 1920, finding both could look normal but still contain pathogenic organisms, including Clostridium botulinus.
California canned foods have been the source of about 40 deaths in other states, according to the California Department of Public Health. The California State Board of Health responded to the 1919 outbreak with emergency regulation of olive production on Aug. 7, 1920, requiring sanitation through the processing facility and mandating a thermal process.
Heat treatment for olives after cans or jars are sealed to sterilize contents completely was required. Immersion in water at 240 degrees Fahrenheit for 40 minutes was the rule.
California canned olives continued to poison people in some scattered cases.
The emergency regulations under the California Pure Foods Act and limited staff to enforce them were not enough.
California responded with the Cannery Inspection Act of 1925. Both the State Board of Health and the National Canners' Association supported it, which by then even favored federal inspection.
California's Food and Drug Branch today inspects 200 licensed canners where regulated products are packed. It's primary goal remains preventing foodborne botulism. Tests for retort operators to determine qualifications to operate sterilization equipment are critical.
Dr. Armstrong continued to serve in the uniformed U.S. Public Health Service until 1950, ending up as Chief of the Division of Infectious Disease. In Warm Springs, GA, a sculpture of his likeness is found in the Polio Hall of Fame. He is recognized for being the first to adapt and transmit the human strain of poliovirus to small rodents from monkeys, a key step in the development of vaccines.
As for Mrs. I.W.G., her death by Botulism was probably known to her friends and neighbors in Sebring at the time, but she remains known 87 years later only by those initials assigned to her by Dr. Armstrong.
CDC reported that half of the foods implicated in outbreaks were imported from "areas which previously had not been associated with outbreaks." The research was presented at the International Conference on Emerging Infectious Diseases in Atlanta. 
