Judicious Use of Antimicrobials


How the most powerful treatment against bacterial infection is becoming obsolete


Astew of bacteria constantly sloshes around in our guts. Most of it is supposed to be there, helping to digest food and absorb nutrients.

There are harmful bacteria as well that can cause infections, in the gut and all over the body. Before the use of antibiotics became widespread in the 1940s, maladies such as a sore throat or even a small cut that became infected could wind up causing death.

Antibiotics were (and still are) miracle drugs, but biology adapts, and in the 87 years since Alexander Fleming discovered penicillin, bacteria have continuously evolved, developing new defenses against attack. In fact, by 1946, 18 years after Fleming’s discovery, an estimated 14 percent of one particular bacterial strain was already resistant to penicillin. Since then, the dance has continued: scientists identified more antibiotics, and bacteria continued to evolve. But now, thanks to what some experts call unethical use of antibiotics in humans and animals, the multitude of varieties of bacteria may be outpacing our efforts to control them. Time may be running out for the world’s defenses against bacterial infections.

In 2014, the World Health Organization released its first report on the worldwide threat of antibiotic-resistant bacteria, saying that without a coordinated plan of action, we are headed for a post-antibiotic era.

For some people, that era is already here, says Dr. Guy Palmer, Regents Professor of Pathology and Infectious Diseases and the Senior Director of Global Health at Washington State University. According to a 2013 report from the Centers for Disease Control, 2 million people become infected with antibiotic-resistant bacteria every year, and at least 23,000 die from the infections.

“Antibiotics are an amazing part of medical history,” Palmer says. “But resistance to them by bacteria is also a fact. It’s inevitable, but the speed with which it occurs could be preventable.”

Consider the impact of a “post-antibiotic era” on health care as we know it: Procedures that define the heights of medical advances — such as bone-marrow transplants, cardiac bypasses and joint replacements — will become much riskier, possibly too risky to attempt; chemotherapy will become a challenge, as patients with weakened immune systems won’t be able to count on protection against infection; and people with common illnesses ranging from strep throat to gonorrhea to a urinary tract infection may no longer be able to go to the doctor, get a prescription and walk out confidently, assuming their symptoms will soon be gone.

“Health care in the 21st century is built on the back of antibiotics,” says Dr. Scott Weissman, assistant professor at Seattle Children’s Hospital and the medical director for the Antimicrobial Stewardship Program. “Antibiotic resistance has changed the way we manage otherwise healthy people with infections, and is making decisions that were once routine much more difficult.”

How did this happen?

Fleming won the Nobel Prize in 1945 for his groundbreaking discovery, but he emphasized that misuse of the drug would allow bacteria to mutate, rendering penicillin ineffective. At his Nobel lecture, he gave the example of a man with strep throat who didn’t take enough penicillin — he took a course of medicine that killed some, but not all, of the insidious bacteria. The remaining bugs developed defenses against penicillin and passed those traits to their descendants. The man infected his wife, and she died from the infection.

“If you use penicillin, use enough,” Fleming said at the time.

Resistance is hastened when antibiotics are not prescribed correctly — in the right amount, for the right amount of time or for the right infection. In those cases, the resistant bacteria survive and can begin to multiply — sometimes at the rate of a new generation every 15 to 20 minutes — passing along their defense mechanisms and quickly creating an army of superbugs.

With all the evidence of increasing antibiotic resistance, it would seem that antibiotic prescription would be taken exceptionally seriously. That isn’t always the case. “It comes down to physicians being anxious about a patient because they’re uncertain about a diagnosis, or maybe the patient is expecting antibiotics and the physician wants to please them as a customer,” Weissman says. In fact, the Centers for Disease Control estimates that up to a whopping 50 percent of antibiotics in hospitals are not “optimally prescribed.”

It’s not always easy to determine the best course of action in patients whose lives, and illnesses, are playing out in real time. For example, it might seem simple to advocate using antibiotics in a life-or-death situation, but it’s much more challenging to determine the best course of action when things are less obvious; occasions in which a physician is unsure of the diagnosis and opts to first protect the patient by using a powerful, broad-spectrum antibiotic, rather than waiting to choose a more targeted antibiotic with a smaller spectrum of destruction.

Palmer says there is very little quantitative data surrounding this discussion, a hole his team of researchers at Washington State University is hoping to fill.

One bad bug

Hospitals throughout the state, including in Spokane, voluntarily track a number of bacteria, according to Carol Wagner, senior vice president of patient safety with the Washington State Hospital Association. There are two types of antibiotic resistant bacteria that state law requires care centers, labs and health care providers to report. The first is Vancomycin-resistant Staphylococcus aureus (VRSA). The second is a particularly virulent group of superbugs known as carbapenem-resistant Enterobacteriaceae (CRE). This group releases potent enzymes that destroy the very antibiotics sent to attack them, rendering what Weissman calls “the most powerful antibiotic in the history of mankind” powerless.

The bacteria can wreak havoc, causing a wide range of infections, from the urinary tract to the bloodstream to the lungs. According to the CDC, the mortality rate for these kinds of infections is 40 to 50 percent.

What is Washington state doing?

The Washington State Department of Health has recognized Palmer’s and others’ claims that antibiotic resistance is not a one-dimensional issue. To that end, the department has joined with 10 other groups of stakeholders, including universities and state health departments, to combat the issue. It’s known as the “One Health” approach.

“The approach means people who’ve never talked to each other are talking now,” says Dr. Marisa D’Angeli, medical epidemiologist for the Department of Health. “That’s a really important part of tackling this problem.”

D’Angeli points to a push for the collection of bacterial resistance data in humans, animals and the environment. Once researchers have the data, they’ll have a better understanding of what resistance exists in the state, and how it’s changed over time.

Although bacterial adaptation is inevitable, we do have control over how quickly it happens, Palmer says. Antibiotic stewardship programs like the ones throughout hospitals in Spokane are key examples of how to gain control.

As a clinical pharmacist at Providence Sacred Heart Medical Center, Mariesa Durrant’s job is to constantly monitor antibiotic use throughout the hospital. That means tracking which antibiotics patients are given, how much they’re given and for what amount of time. It also means re-evaluating whether the original prescription should be changed.

“Appropriate use means the right antibiotics for the infection you have, and using them for the right amount of time,” Durrant says. “It’s specific for every patient and every type of infection.” ♦

New antibiotics on the horizon?

Researchers at Northeastern University in Boston discovered a new antibiotic without any detectable resistance earlier this year. The discovery marks the first major revolution in antibiotic resistance in decades, though the drug, teixobactin, has only been tested on mice. Human tests are at least two years away, and the drug is another five or six years from market.

Despite the breakthrough, the wider scene of antibiotic development isn’t booming. According to the Washington State Department of Health, new antibiotic approvals by the FDA have declined significantly since the 1980s, although two new antibiotics were approved this year.

It’s an expensive and time-consuming process, says Dr. Guy Palmer, Regents Professor of Pathology and Infectious Disease and Senior Director of Global Health at WSU. For pharmaceutical companies, the expense often doesn’t outweigh the potential profit.

In recognition of this issue, President Obama signed a law in 2012 that extended by five years the amount of time pharmaceutical companies have exclusive rights to sell antibiotics without competition from generic brands.

Although he says new antibiotics are necessary, Dr. Scott Weissman, assistant professor at Seattle Children’s Hospital, also says that in order to fully address the problem, “the new antibiotics will have to be introduced in a setting where antibiotic stewardship practices are in place.”


Antibiotic ethics

– Take the full dose of antibiotics prescribed to you, even when you start to feel better. If you don’t, you risk enabling some of the bacteria to develop resistance, survive and thrive.

– Don’t take other people’s antibiotics: A physician prescribed a type and dose specific to your infection. “Antibiotics are for a course of therapy, and you might feel better, but by not completing the course, you’re lowering the chance of not killing off the infection,” says Mariesa Durrant, a clinical pharmacist at Providence Sacred Heart. “That affects your current infection, as well as ones in the future.”

– Don’t expect an antibiotic from a physician. Some infections, such as viruses, can’t be treated with antibiotics. Taking them unnecessarily only exacerbates the antibiotic resistance problem and won’t help you.

– Wash your hands: It helps stop the spread of bacteria.

– Get a flu shot every year. Even though the flu is a virus, which is not treatable with antibiotics, contracting it can leave you vulnerable to bacterial infections.


Antibiotics and animals

Antibiotics given to animals contribute to the problem of antimicrobial resistance, but according to Dr. Guy Palmer, Regents Professor of Pathology and Infectious Disease and Senior Director of Global Health at Washington State University, this is a much bigger problem throughout the rest of the world than in the United States.

Before the U.S. Food and Drug Administration started regulating the amount and type of antibiotics administered to food animals, cows, pigs and chickens in the U.S. were given feed that contained antibiotics, because they help stave off infection and help the animals grow. The animals then became a breeding ground for antibiotic-resistant bacteria. Those germs could infect humans through improperly prepared meat. Fertilizer and water containing trace amounts of animal feces also could infect humans.

In 2012, the FDA instituted guidelines requiring sponsors of animal drugs to remove packaging labels on feed that say antibiotics promote animal growth. In June of this year, the FDA finalized a policy that requires veterinarians to authorize the use of antibiotics in animals.

“That’s a fairly major change,” Palmer says, but he adds that changing the amount of antibiotics given to animals in the U.S. is a small fix for a much larger problem. The practice is still rampant in other countries, especially in the rural areas of India and China.

“The change puts the U.S. in a leadership position,” says Palmer, “but it’s naive for anyone to think this is the solution.”



Public Universities/Veterinary Medical Colleges’ Task Force Unveils Recommendations & Launches Action Plan
to Address Antibiotic Resistance in Production Agriculture

WASHINGTON, DC / October 29, 2015

The Association of Public and Land-grant Universities (APLU) | Association of American Veterinary Medical Colleges (AAVMC) Task Force on Antibiotic Resistance in Production Agriculture today unveiled a much-anticipated report that outlines a comprehensive national strategy for diminishing the role antibiotics used in food animal production systems play in the broader antimicrobial resistance (AMR) problem.

The Task Force, comprised of leaders from U.S. agriculture colleges/land grant universities and veterinary colleges as well as key representatives from the production animal agriculture community and the pharmaceutical industry, detailed a comprehensive research and educational agenda along with plans on how it intends to implement it.

The report’s agenda is designed to explore and describe the nature and implications of the problem and educate producers, healthcare providers and the public about best practices. It also calls for a series of national summits to elevate the issue of antibiotic resistance to the top of the national agenda.

Formed last fall, the 14-member task force has been working closely with federal government agencies to develop an action plan that will leverage the collective strengths and expertise of North American universities to address what the Obama administration has termed a national security priority.

“We know that antibiotic resistance is biologically complex and poorly understood,” said Dr. Lonnie King, a former dean of The Ohio State University College of Veterinary Medicine and former senior Centers for Disease Control and Prevention (CDC) official who co-chaired the task force with University of Illinois President Emeritus Robert Easter. “We also know that the scope and scale of the problem threatens human, animal and environmental health, nationally and globally. The committee has accomplished some important work, but now we need to take action.  Solving this problem is going to require focus, resources, collaboration and sustained effort.”

The Task Force report also contains a detailed strategy for implementing their educational, outreach and research program recommendations. A full-time program manager has been hired to provide administrative leadership and management. The APLU and AAVMC will work to identify a national consortium of faculty experts within their member institutions to build out the programs and collaborate with federal agency personnel.

A centralized University Research Organization (URO) is envisioned to serve as a coordinating center for the educational and research programs that need to be created and operated. The URO would engage the full complement of stakeholders in a public-private partnership that would serve as the focal point for a sustained, consolidated research and educational effort. Though physically housed within a single academic institution, the URO would have a supra-organizational governing body, scientific advisory council, and subscription membership available for pharmaceutical companies, commodity organizations and others engaged in the fight against antibiotic resistance.

Pilot projects focused on combating antibiotic resistance will be created at several large universities with substantial human medical, veterinary medical, and agricultural centers.

A series of educational workshops and leadership forums uniting personnel from federal agencies, industry, NGO’s and academic institutions will be convened to explain and advance the Task Force recommendations. Other strategies designed to support the successful implementation of the Task Force recommendations include:

  • Frequent collaboration/meetings with USDA, FDA, CDC, PCAST representatives, agricultural and veterinary medical organizational, federal task force officials to ensure coordination and alignment
  • Broad collaboration with representatives from the OIE, FAO, WHO and other global organizations with interest and programs in this area
  • Engagement with federal government agencies to resolve the issue of lack of veterinarians in many rural communities across the United States

Antibiotic-resistant bacteria, according to the CDC, cause at least 2 million illnesses and 23,000 deaths in the United States every year. Infections caused by these pathogens cost an estimated $20 billion a year in direct health care costs and up to $35 billion in lost productivity as a result of hospitalizations and sick days. The growing public health threat has prompted action on a number of fronts.

Following the “Combating Antibiotic Resistance” report published in September 2014 by the President’s Council on Advisors on Science and Technology, an Executive Order was issued by the administration to create a five-year National Action Plan. Critical features of the plan include 1) slowing the spread of resistant infections, 2) strengthening One Health surveillance efforts, 3) developing improved diagnostic tests, 4) accelerating research and development, and 5) improving international collaboration.

The AAVMC | APLU Task Force report will be broadly disseminated among the vast array of stakeholders involved with the issue. King’s recent appointment to co-lead the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria will help ensure that the APLU/AAVMC Task Force recommendations are fully considered as elements of the official national action plan.

To develop the report, task force members convened with federal government officials in Washington several times. The report outlines the benefits of leveraging the research and development capabilities of the nation’s universities, as well as the working relationships maintained by faculty members at the nation’s land-grant universities with members of the production animal community through the USDA’s Cooperative Extension Service.

“Solving problems through the production and application of knowledge is a key role of colleges and universities in society,” said Peter McPherson, president of APLU. “This is a big challenge with global implications, but it is one our land-grant and public universities are well-qualified to address. Our universities can conduct the research that must be undertaken and transmit the information that must be shared. I think we’ve taken a significant step forward, and we look forward to building on this progress.”

Veterinarians play a critical role in the success of the effort because of their expertise in both animal and public health. Their role in animal agricultural production has become even more important following the Food & Drug Administration’s recently issued Guidance(s) 209 and 213 and the Veterinary Feed Directive, which enhance veterinary oversight of antibiotics used in animal production. Most of the nation’s colleges of veterinary medicine are located at Land-grant universities.

“Our task force has focused on the role animal agriculture is playing in this problem and our colleges of veterinary medicine play an instrumental role in those agricultural production systems,” said Dr. Andrew T. Maccabe, executive director of the AAVMC. “Effective solutions are going to require a collaborative approach, and one of the great strengths of this task force report is that it includes perspectives and contributions from government, academia and industry.”

APLU is a research, policy, and advocacy organization representing 237 public research universities, land-grant institutions, state university systems, and affiliated organizations. Founded in 1887, APLU is North America’s oldest higher education association with member institutions in all 50 U.S. states, the District of Columbia, four U.S. territories, Canada, and Mexico. Annually, APLU member campuses enroll 4.7 million undergraduates and 1.3 million graduate students, award 1.1 million degrees, employ 1.3 million faculty and staff, and conduct $41 billion in university-based research.

The Association of American Veterinary Medical Colleges (AAVMC) is a nonprofit membership organization working to protect and improve the health and welfare of animals, people and the environment by advancing academic veterinary medicine. Members include 49 accredited veterinary medical colleges in the United States, Canada, Europe and Australia, as well as 23 affiliate members.

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