Antimicrobial Stewardship – what’s that?

Do you know that the world is facing an unprecedented crisis? Antimicrobial resistance kills ~700,000 people globally every year!

*Antimicrobials include anti-virals, anti-biotics, anti-fungals and anti-parasitics. We will only address antibiotics in this blog post, since these are the most prescribed antimicrobials.

Research shows that TOTAL inappropriate antibiotic use (i.e. both unnecessary antibiotic use AND inappropriate antibiotic selection, dosing, and duration) may actually be 50% of all outpatient antibiotic use!

However, this may be an underestimation, since these studies do not take into account

  • antimicrobials acquired without prescriptions, which include
    • sharing among friends and family
    • antimicrobials obtained over the counter, legally in many countries and illicitly in the United States.

Even in hospitals, 30 – 50% of prescribed antibiotics are unnecessary or inappropriate

Approximately 3 million pounds of antibiotics are used by humans annually.

  • Most of these in outpatient setting.

Approximately 30 million pounds of antibiotics a year are used by food animals:

  • for growth promotion, and
  • for treatment or prevention of diseases.

This heavy use of antibiotics creates an environment that enables antibiotic-resistant bacteria with a potential survival advantage.

Many antimicrobials used in food animals belong to the same classes that are used in humans!

  • This raises concerns about cross-resistance. 
    • For example, avoparcin (similar to vancomycin) has been used in Europe for
      • growth promotion of food animals, since the 1970s.
  • Vancomycin-resistant enterococcus (VRE) was first described in 1988.
    • VRE has since been isolated from food animals in Denmark and Germany, among other countries.
      • Epidemiology reveals a link with avoparcin use.
  • The same VRE strains have been found in animals and humans.

Intestines, ours as well as that of other animals, harbor a large community of microorganisms.

  • When an antibiotic is given to animals, it kills most bacteria that are in the intestines of the animals.
  • Resistant bacteria survive the antibiotic and
    • in the absence of competition from the other microorganisms that got killed, they start increasing in numbers.

Heavy and frequent use & misuse of antibiotics in humans and food animals, has created antibiotic resistant bacteria in large numbers. Antibiotic resistant bacteria spread from animals. via animal products that are contaminated with intestinal bacteria. Subsequent spread occurs via

  1. Unclean meat processing, or unclean worker hands.
    • You have heard of O157:H7.
    • These are Escherichia coli bacteria that are found in the gut of animals,
      • but make their way into meat sometimes (like hamburger meat for instance) and
        • end up making people very ill and at times even kill them.
  2. When our food animals defecate on the farm, the environment gets contaminated with their fecal bacteria.
    • The surrounding soil can get contaminated or workers’s hands can get contaminated.
      • The end result is, even vegetables that are being grown on the farm, can now get contaminated.
        • ……hence, the recent contamination of lettuce with O157:H7 E. coli.

Infections with antibiotic resistant bacteria cause mild illness OR at times severe illness that may be fatal.

  • About 1 in 5 resistant infections are caused by germs from food and animals.

IS ANTIBIOTIC RESISTANCE NATURALLY FOUND?

Metagenomic (meaning straight from the environment) research reveals presence of antibiotic resistance genes in ancient sediments isolated from 30,000 year old permafrost (permanently frozen) cores from the Yukon valley of Alaska.

  • Scientists looked specifically for several contemporary antibiotic resistance elements and found
    • beta-lactamase &
    • tetracycline resistance genes, in addition to
    • vancomycin resistant genes.

Interesting thing about vancomycin resistance?

  • It requires expression of at least 3 genes acting together:
    • the permafrost core had all 3 genes!
  • These resistance genes even coded for enzymes with the same biochemical activity and structure as that found today!

My own research has shown that we don’t even need antibiotics to turn on antibiotic resistance genes!

These genes exist in nature and get turned on by antibiotics and other chemicals.

Is antibiotic resistance inevitable? Why or Why not?

Soil bacteria and fungi are nature’s antibiotic producers.

  • These antibiotic producers have to also create antibiotic resistance mechanisms
    • so they are not killed by the antibiotics they produce and release into the environment.

So, antibiotic resistance is not only ancient, but antibiotic resistance is also inevitable!

CAN WE REVERSE ANTIBIOTIC RESISTANCE?

  • Antibiotics target bacterial structures and functions that are essential to bacteria, and therefore, highly conserved.
    • Antibiotic resistance will attempt to modify these highly conserved, bacterial targets.
      • HOWEVER, changes to these highly conserved targets are often deleterious to the antibiotic resistant, bacterial mutant.
        • This has consequences for the mutants. 
          • These antibiotic resistant bacteria have a disadvantage, when you compare them with non-resistant bacteria, i.e. antibiotic susceptible bacteria.
            • The resistant bacteria don’t grow as well as the non-mutated bacteria.
          • IF you REMOVE the antibiotic, you will now enable MORE of the non-mutated (i.e. antibiotic susceptible) bacteria to start growing 

This means, WE MAY BE ABLE TO REVERSE ANTIBIOTIC RESISTANCE OVER TIME, in the absence of the antibiotic. But, we may not be able to completely eliminate the resistance genes from nature. Perhaps we can recycle antibiotics every few years or so, but not use them continuously. By taking antibiotics out of circulation, we can allow resistance to go down. Researchers are studying this theory.

The goals of threat-specific CDC activities are to:

  • to determine the epidemiology of the infectious agent
  • to remove gaps in ability to detect antibiotic resistance, and
  • to protect against these infections.

CDC URGENT THREATS

  • may not be currently widespread, but, can be widespread
  • require urgent public health attention to
    • identify these threats and to limit transmission
  • Examples:
    • Clostridium difficile, Carbapenem resistant Enterobacteriaceae (CRE), and Drug resistant Neisseria gonorrheae (cephalosporin resistant)

Clostridium difficile has a new name: Clostridioides difficile

Antibiotics Can Cause More Harm than Good

Taking antibiotics when you don’t need them, increases your risk of getting an antibiotic-resistant infection later.

  • Antibiotics also kill our healthy gut bacteria, allowing more harmful bacteria such as Clostridioides difficile (aka C. diff aka C. difficile), to grow in its place.
    • Although C. diff infection is more commonly found in hospitals, it also occurs in clinics outside of the hospital.
    • Most at risk of C. diff are people (esp. older adults) who take antibiotics & also get medical care in clinics, outpatient centers, hospitals etc.

What precautions will YOU take if YOUR patient has C. diff and you are taking care of her?

C. diff causes life-threatening diarrhea

  • Infections mostly occur in people who have had both recent medical care and antibiotics.
  • Often, C. difficile infections occur in hospitalized or recently hospitalized patients.
  • Improving antibiotic prescribing can actually reduce harm.

Research studies show that a 10% decrease in inappropriate antibiotic prescribing in the community has been shown to lead to a 17% reduction in C. diff infection.

CDC SERIOUS THREATS

  • not considered urgent
    • but will worsen and
      • may become urgent without ongoing public health monitoring and prevention

These threats include

  • multidrug resistant Acinetobacter, drug resistant Campylobacter, fluconazole resistant Candida, extended spectrum beta-lactamase producing Enterobacteriaceae, vancomycin resistant Enterococci, multidrug resistant Pseudomonas aeruginosa, drug resistant non-typhoidal Salmonella, drug resistant Salmonella typhi, drug resistant Shigella, MRSA, drug resistant Streptococcus pneumoniae, and drug resistant tuberculosis (MDR and XDR).

CDC CONCERNING THREATS

  • The threat of antibiotic resistance is low, and/or
    • there are
      • multiple therapeutic options for drug resistant infections.
  • These threats require monitoring,
    • and in some cases,
      • rapid incident or outbreak response.
  • These bacterial pathogens cause severe illness.

These threats include

  • vancomycin resistant Staphylococcus aureus (VRSA)
  • erythromycin resistant Group A Streptococci
  • clindamycin resistant Group B Streptococci

Carbapenem Resistant Enterobacteriaceae (CRE) infections

  • CRE infections are rare in the United States (U.S.).
  • CDC does not require that hospitals report CRE cases.
  • In 2017, 239 cases in the U.S. were reported to the CDC.
    • The majority of CRE cases still respond to 1 or 2 classes of antibiotics…..
      • for now!
  • Unfortunately, CRE infections show more than 50% mortality 
    • which means, more than half of infected individuals will die from these infections.

If undiagnosed and untreated, Gonorrhea can cause complications such as:

  • Pelvic inflammatory disease (PID)
    • gonococci spread to uterus or fallopian tubes
    • PID can lead to
      • chronic pelvic pain,
      • infertility, and
      • increased risk of ectopic pregnancy,
        • which can be life threatening.
  • Epididymitis
    • although rare, can cause infertility
  • disseminated gonococcal infection
    • is life threatening
  • Increased risk of HIV infection.

Of the 820,000 gonococcal infections per year in the United States, 246,000 are drug resistant.

Goals of antimicrobial stewardship (AMS) in a nutshell:

  • To maximize the benefit of antibiotics, while minimizing harm to both the individual and the wider community.
  • To minimize antibiotic resistance.
  • To decrease toxicity, adverse drug reactions & C. diff diarrhea.

Antibiotics Can Cause More Harm than Good

  • 1 out of 5 emergency department (ED) visits are for adverse drug events.
    • Antibiotics are the most common cause of ED visits for adverse drug events in
      • children less than 18 years of age.
  • If we don’t take antibiotics only for bacterial infections,
    • we are putting ourselves at risk for
      • harmful side effects and
        • antibiotic-resistant infections.

WE NEED TO DO THE FOLLOWING:

  • ASK
    • Do I really need antibiotics? 
  • Say YES only for certain bacterial infections.
  • Antibiotics CANNOT and WILL NOT CURE viral infections like
    • flus and colds;
    • runny noses even when mucus is thick, yellow or green;
    • most cases of bronchitis;
    • many sinus infections; and
    • even some ear infections.

Do you know hand hygiene is the single most important way to prevent infections?

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