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Syndromic Testing

Overcoming the threat of antimicrobial resistance

By QIAGEN Syndromic Testing

Antimicrobials are crucial for modern medicine, and diseases that were once deadly are now treatable. But the overuse or misuse of antimicrobials can lead to antimicrobial resistance. Experts predict that by 2050, deaths due to antimicrobial resistant infections will surpass those of cancer. However, improved diagnostic accuracy can help us fight this ongoing threat.  

A few years ago, Prof. Neil Woodford, head of antimicrobial resistance for Public Health England (PHE), noted an alarming trend (1).

The number of drug-resistant infections making it to PHE’s labs was growing.

“If we go back to 2005/07, we were seeing these bacteria in maybe two to four cases per year,” Woodford said. “Last year (2016), we confirmed these resistant bacteria in over 2,000 cases.”

Global antimicrobial resistance, particularly in respiratory infections, is growing. According to PHE, by 2050, drug-resistant infections will kill more people annually than cancer (1).

In the U.S., the Centers for Disease Control and Prevention (CDC) attributes 2.8 million infections each year to antimicrobial resistance (2).

And the World Health Organization (WHO) found in 2017 that drug-resistant Streptococcus pneumoniae is responsible for 20–30% of pneumonia cases in children each year (3). The organization blames penicillin-resistant Streptococcus pneumoniae on 30–40% of childhood pneumonia cases.

Antimicrobial resistance (AMR) can lead to death, poorer patient experiences and increased healthcare and health services costs (4).

The expanding crisis is prompting public health officials to sound the alarm and encourage the medical community to take action.

The CDC attributes 2.8 million infections each year to antimicrobial resistance (2).

In late 2020, the Centers for Disease Control and Prevention (CDC) released the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria (National Action Plan) (5). The WHO lists AMR as one of the world’s most significant health threats.

Since their introduction in the 1940s, antibiotics have revolutionized medicine. Now, though, overusing antibiotics threatens to undo many of modern science’s gains.

Causes of AMR

Bacteria and fungi are living organisms that adapt when encountering something that threatens their existence. The more bacteria and fungi interact with antibiotics, the more they evolve to resist these drugs’ effects.

As antibiotic use increases, so does this resistance, AMR. And there are many culprits to blame for growing AMR:

  • Overprescribing antibiotics
  • Limited hospital-level regulation of antibiotic use
  • Antibiotic and antimicrobial use in food-producing animals
  • Greater availability of antibiotics in developing countries
  • Poor-quality antibiotics in developing countries 

The CDC released data in 2019 showing that 79% of patients with community-acquired pneumonia would get better without antibiotics. The agency also said that about 30% of antibiotic use in acute U.S. hospital stays was “either unnecessary or suboptimal” (6).

Patients may bear at least some responsibility for overprescribing antibiotics.

A 2016 survey found that 70% of Americans didn’t think AMR was a serious problem. Meanwhile, 40% of the survey’s respondents said that antibiotics were needed to treat a fever, sore throat or runny nose (7).

On the agriculture side, a 2013 Food and Drug Administration (FDA) study discovered that sales of microbials for use on food-producing animals increased by 26% from 2009 to 2015. In 2016, the agency found that 96% of antimicrobials were sold over-the-counter without needing a veterinarian’s prescription (8).

In developing countries, increasing antibiotic availability is contributing to AMR.

A 2003 Chinese study found that out of 1,025 cases in which antibiotics were prescribed, only 39 received a microbiological examination beforehand. In these cases, 77.8% of patients were prescribed at least one antibiotic (9).

And the quality of available antibiotics in developing nations is also playing a part in AMR’s growth. Unfortunately, some antibiotics in these countries are relabeled, improperly stored or are counterfeit drugs that contain no active ingredients.

These multiple contributors lead to costly, deadly outcomes for patients and healthcare systems.

Benefits of Reducing Inappropriate Antibiotic Use

Each year, about 700,000 people die because of drug-resistant infections. Twenty-three thousand of these occur in the U.S. and 25,000 in the European Union (10).

Patients suffering from antibiotic-resistant infections may require extended hospital stays and time in intensive care units or isolation beds to prevent the spread of disease.

AMR can prevent patients from receiving organ transplants, impacting treating cancer patients. If AMR is present, a patient who has cancer may not be able to receive chemotherapy since that treatment lowers their immune defenses and makes them more susceptible to infection.

Each year, about 700,000 people die because of drug-resistant infections (10).

These impacts are taking a financial toll on patients and healthcare systems.

The CDC estimates AMR adds about $1,400 to a patient’s hospital bill in the U.S. In addition, the agency says AMR is adding $20 billion to annual health care costs.

Worldwide, various studies show that AMR costs may reach between $300 billion and $1 trillion by 2050 (11).

AMR also contributes to global economic decline as more people suffer or die from antibiotic-resistant infections.

Some studies show that AMR could cause the annual global GDP to drop by 1% and 5–7% in developing countries by 2050. This amounts to a loss in global yearly GDP of $28 billion in ten years if nothing is done to address AMR (12).

But public health organizations around the globe are trying to address the problem.

In the U.S., the federal government is rolling out the National Action Plan for Combating Antibiotic-Resistant Bacteria.

National Action Plan

As global concern for AMR mounted, in 2015 the U.S. government released its first National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB).

Then, in late 2020, the government issued an updated plan for coordinating interagency efforts to combat AMR through 2025. The revised CARB incorporates the latest research showing effective ways to stem AMR, including improving how antibiotics are used and increasing infection prevention.

CARB is an all-out effort among U.S. government agencies to better understand and counteract AMR in collaboration with international governments and organizations.

CARB encompasses five goals:

  1. Slow the emergence of resistant bacteria and prevent the spread of resistant infections
  2. Improve surveillance efforts to combat AMR
  3. Promote the development and use of rapid and innovative diagnostic tests for identifying resistant bacteria
  4. Accelerate basic and applied research and development for new antibiotics, other therapeutics and vaccines
  5. Strengthen international collaboration and capacities for AMR prevention, surveillance, control and antibiotic research and development
The National Action Plan for Combating Antibiotic-Resistant Bacteria recognizes diagnostic testing’s pivotal role in dealing with AMR.

The third goal, developing rapid molecular diagnostic testing tools, focuses on the need for greater detection of antibiotic resistance and to improve the information health providers receive about a patient’s condition.

CARB recognizes diagnostic testing’s pivotal role in dealing with AMR while acknowledging the need for more research and information to understand diagnostics’ impacts better. The plan also realizes some of the challenges companies face when developing new diagnostic tests, including high costs and adoption rates.

CARB tackles three objectives to accomplish its goal of promoting the development and use of diagnostic tests for AMR identification:

  • Develop and validate new diagnostics
  • Support research to determine the appropriate use of diagnostics
  • Stimulate the proper adoption and use of diagnostics

Conclusion

Antimicrobial resistance is a growing global issue that can lead to poorer health outcomes, including death, and increased medical costs. AMR-related health expenses could reach $1 trillion by 2050.

But the Centers for Disease Control and Prevention has a national plan for fighting antimicrobial resistance. The National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) has among its goals increased use of diagnostic testing to better equip health providers with critical patient information.

If successful, CARB will enable more medical professionals to use new and improved diagnostic testing to stem the tide of antimicrobial resistance.

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References
  1. Gallagher, James. “Patients Need Rest, Not Antibiotics, Say Health Officials.” BBC News, BBC, 22 Oct. 2017, https://www.bbc.com/news/uk-41696236.
  2. “Core Elements of Hospital Antibiotic Stewardship Programs.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 16 Nov. 2020,https://www.cdc.gov/antibiotic-use/core-elements/hospital.html.
  3. Ramanan, P., Bryson, A. L., Binnicker, M. J., Pritt, B. S., & Patel, R. (2017). Syndromic Panel-Based Testing in Clinical Microbiology. Clinical microbiology reviews, 31(1), e00024-17. https://doi.org/10.1128/CMR.00024-17
  4. Banerjee, R., Teng, C. B., Cunningham, S. A., Ihde, S. M., Steckelberg, J. M., Moriarty, J. P., Shah, N. D., Mandrekar, J. N., & Patel, R. (2015). Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 61(7), 1071–1080. https://doi.org/10.1093/cid/civ447
  5. Shorr, A. F., Micek, S. T., Welch, E. C., Doherty, J. A., Reichley, R. M., & Kollef, M. H. (2011). Inappropriate antibiotic therapy in Gram-negative sepsis increases hospital length of stay. Critical care medicine, 39(1), 46–51. https://doi.org/10.1097/CCM.0b013e3181fa41a7
  6. Thornberg, Adam. “The Right Test at the Right Time during the SARS-CoV-2 Pandemic.” MLO, https://www.mlo-online.com/diagnostics/assays/article/21158898/the-right-test-at-the-right-time-during-the-sarscov2-pandemic