Federal Mandate to Control and Reduce Antibiotic Resistance

To:  Dr. Jerome Adams – Surgeon General of the United States
From:  Markenzie Jean-baptiste
Date:  January 15, 2019

Problem Statement:

What prevention strategy should be implemented as a top priority to control and reduce the rates of antibiotic resistance?

Background:

Overutilization of antibiotics is one of the biggest causes of antibiotic resistance. Antibiotics were once thought to be a miracle drug when they were first used in the 1940’s. The effectiveness of antibiotics to treat harmful bacteria since has caused them to be over utilized in healthcare and the food industry. As a result, bacteria have increasingly evolved to become resistant to most of the available antibiotics we have left, increasing the incidence antibiotic resistant infections.

The CDC estimates that 23,000 Americans die from antibiotic resistant infections each year and 2 million suffer antibiotic related illnesses yearly (1). Methicillin-resistant Staphylococcus aureus(MRSA) causes life threatening infections for patients in healthcare settings, and can even also be acquired in local communities around the US(3). It kills more than 19,000 people annually (2). Another bacteria, Clostridium difficile causes life threatening diarrhea and colitis, killing 15,000 people annually. It mostly affects people who have had both recent medical care and antibiotics. Drug resistant Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea and has increasingly developed resistance to the antibiotic drugs used to treat it(3). Carbapenem-resistant Enterobacteriaceae(CRE) is a family of bacteria that are resistant to nearly all antibiotics including carbapenems. This is extremely important to note because carbapenems are often considered the antibiotics used by physicians as a last resort when all other options fail (3).

The increasing rate of antibiotic resistant infections adds to the total costs of healthcare expenditure in the US yearly. In 2014, it was estimated that 2.2 billion dollars was spent on treating antibiotic resistant infections, which has doubled since 2002(1). These costs are expected to rise even more over time.

Key Contributors to Antibiotic Resistance

The number of pharmaceutical companies conducting antibiotic research has declined, leading to decreased production of new antibiotics. Between 2003-2007, the largest pharmaceutical companies in the US only produced five antibacterial agents (4). Only two new classes of antibiotics have been developed in the last 30 years (5). 97 percent of new drugs being developed have failed to gain Food & Drug Administration (FDA) approval (2).

The Generating Antibiotic Incentive Now (GAIN) provision was signed in 2012 to create incentives to stimulate drug companies to make antibiotics to treat serious antimicrobial infections (17). The Gain Provision would then give drug companies an additional 5 years of exclusivity, fast track and priority review status. Unfortunately, many new drugs being approved after GAIN are just improvements to existing drugs. In order to effectively address antibiotic resistance for the future, drug companies will need to focus on developing new drugs. There is some hope in the future development of alternatives to antibiotics such as antimicrobial vaccines/immunity modulating agents, but this is a controversial issue that requires more research (6).

More than 70 percent of antimicrobial drugs are used in agriculture to prevent diseases in animals, promote animal growth, and make them safer produce in the Meat industry (7). This prevents the incidence of food borne illness but irresponsible use of antimicrobials in food production is also contributing to antibiotic resistance. The country Norway was able to reduce it’s reliance on antimicrobials by 99 percent by introducing an industry wide salmon vaccination program, along with technological advancements and improvements in sanitation and hygiene (7).

Over prescribing of antibiotics by clinicians and over utilization by patients are leading contributors to antibiotic resistance. Studies have shown that outpatient and community-based care have the highest rates of inappropriate prescribing of antibiotics with 20 to 50 percent of antibiotic prescriptions being unnecessary (8). 44 percent of outpatient antibiotic prescriptions are prescribed to treat patients with acute respiratory conditions like sinus infections, pharyngitis, and bronchitis (9). The issue here is that half of these are not necessary because viral illnesses do not respond to antibiotics. Patient demands, inadequate time to explain to patients why antibiotics are unnecessary, and misdiagnoses of non-bacterial infections contribute to these prescribing practices (8). Many patients also stop taking antibiotics abruptly or use them inappropriately, further increasing the rates antibiotic resistance.

To address the rise in antibiotic resistance, many health care organizations have implemented antibiotic stewardship/monitoring programs. The programs monitor the prescribing patterns of providers; ensuring antibiotics are prescribed with proper dosage and the least duration necessary to get the best clinical outcomes for patients (10). Some features of antibiotic stewardship/monitoring programs are the following:

• Prospective audit of antibiotic use– allows providers to autonomously prescribe antibiotics for a patient but also get direct feedback from an infectious disease physician or pharmacist with infectious disease training (especially for small hospitals/outpatient centers) (10). Prescriptions can be shortened if needed after the audit. A large teaching hospital reported a 37% reduction in the number of days of unnecessary antibiotics by decreasing duration of treatment and reducing the amount of times patients started new antibiotics (10).
• Formulary restrictions/ preauthorization- requires providers to obtain approval from insurance plans before allowing patients to access antibiotics (11). If the patient does not, the plan will not cover the medication and the patient will have to pay the full cost of the prescription in order to fill the order. Preauthorization requirements can lead to significant reductions in antibiotic use.
• Continuing Education for medical providers on appropriate antibiotic prescribing behavior- Provides free trainings on multiple aspects of prescribing including antibiotic efficacy profile, intravenous to oral conversion programs, side effects, drug-drug interaction, potential for c. diff infection and antibiotic resistance (12). Provide incentives for these trainings like continuing education credits and certificates (13).
• Antibiotic prescribing monitoring- tracks the amount of antibiotic prescribed by providers and healthcare organization altogether.

 

Landscape

Without strengthening measures to control antibiotic utilization, the health of the public is under extreme threat by harmful antibiotic resistant infections. This issue calls for collaboration between key stakeholders to work to mandate antibiotic resistance prevention policies. These policies should focus on three key areas:

 

• Monitoring prescribing patterns of physicians through antibiotic stewardship programs. Collaboration will be needed between federal, state and local health agencies, providers, health insurance plans and health care organizations. Supported by most stakeholders including CDC, FDA, and NIH. Some physicians may be opposed to monitoring their prescribing practices.
• Encourage research and manufacturing of new antibiotics. Funding for pharmaceutical research is largely from for-profit companies/investors in which investments are based off estimated revenue and not necessary perceived public needs (4). Investors less likely to invest in antimicrobial development because their return on investments are lower compared to cancer, neurological or musculoskeletal drugs which are very profitable (14).
• Regulation of the food industries use of antibiotics in agriculture by the federal government and FDA. Lacks support from Meat industry as it can decrease production of meat product and reduce their profits. Federal government is currently in support of phasing out the use of medically important antimicrobials in food production and wants to bring the therapeutic use of these antimicrobials under the oversight by veterinarians. (15).

 

Policy Options

• A federal mandate to require all healthcare organizations to implement an antibiotic stewardship program nationwide. Penalties for non-compliance.
  • Advantages:  Well-supported initiative by most stakeholders involved. Reduction in the amount of antibiotics prescribed. Promote providers to educate patients more about appropriate use of antibiotics as well as danger of antibiotic resistant infections. Projected decrease in antibiotic healthcare costs associated with antibiotic resistance, infection and mortality. Some of it can be funded from hospital revenue through savings as well as through reimbursements from the Centers for Medicare & Medicaid (CMS) Value-Based Purchasing Program (VBP) and the Hospital-Acquired Condition Reduction Program (HAC) (16).
  • Disadvantages:  Costs to implement on a national level. Possibility that decreased antibiotic use could lead to an increase risk for patients who truly have bacterial infections misdiagnosed. Some patients may be opposed if they are denied an antibiotic for a suspected viral illness. A physician’s knowledge and experience working dictate how they will operate under the program. Some may be opposed to the program.
• A federal mandate to ban the use of medically important antimicrobials in agriculture in 5 years nationally and limit antimicrobial use for only veterinary purposes. Will replace antimicrobials with vaccines in similar fashion as the country Norway. Federal government will work with animal drug sponsors to remove antimicrobials in food production. Will also designate veterinarians to oversee that these drugs are being used only to medically treat animals (15).
  • Advantages:  Minimizes inappropriate/unnecessary use of antimicrobials in food production.
  • Disadvantages: Raises the cost and decreases the rate of production of animal produce. Not supported by Meat industry. Federal funding will be needed to fund research effective vaccines, which will take time. Safety and efficacy is not universally established at this time.
• Revise legislation to further increase federal funding and GAIN incentives to pharmaceutical companies that develop maximally beneficial antimicrobials that show proven ability to be effective against antibiotic resistance.
  • Advantages:  Encourages drug companies to target high risk, high reward approaches to antimicrobial manufacturing that might have not been targeted before (14).
  • Disadvantages:  Increased federal government spending. May need to increase public taxes. Likely to be opposed by taxpayers. Increasing incentives does not necessarily mean that maximally beneficial antimicrobials will be made due to the complexity of antibiotic resistance.

Policy Recommendation:

Increasing funding and incentives for antimicrobial research is not of most priority due to uncertainty of actually developing new maximally effective antibiotics in the near future. Banning the use of antimicrobials in food is not of most priority because of competing benefits/harms of antimicrobials in animal food product without alternative solution to address food borne illnesses.

At this time, federally mandating all healthcare organization to implement an antibiotic stewardship program shows the most promise in decreasing the rate of antibiotic resistance. The costs associated to implement on a national level can be offsetted by the savings from reduced antibiotic resistant infections and reimbursements by insurance companies. Essentially, the programs can possibly pay most of the costs for itself. The programs should be accessed yearly to ensure they are effective and being utilized. In addition, the federal government should also fund a national campaign to educate people on antimicrobial resistance and appropriate antibiotic utilization.

 

 

 

Sources:

(1)Antibiotic-Resistant Infection Treatment Costs Have Doubled Since 2002, Now Exceeding $2 Billion Annually. Health Affairs> Vol 37, No 9 Culture of Health, Published March 21,2018     https://www.healthaffairs.org/doi/10.1377/hlthaff.2017.1153

(2) Fleming,New Health Policy Brief: Antibiotic Resistance. Health Affairs, Published May 22,2015         https://www.healthaffairs.org/do/10.1377/hblog20150522.047904/full/

(3) https://www.cdc.gov/drugresistance/biggest_threats.html

(4)A. Kesselheim; Fighting Antibiotic Resistance; Marrying New Financial Incentives to Meeting Public Health Goals. Health Affairs> Vol 29, No 9, Medical Malpractice, Published September 2010   https://www.healthaffairs.org/doi/10.1377/hlthaff.2009.0439

(5)https://www.the-scientist.com/vision/barriers-on-the-road-to-new-antibiotics-48989

(6) Cheng et al. Antibiotic alternatives: The Substitution of antibiotics in animal husbandry. Published online 2014 May 13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026712/

(7)Antimicrobial Resistance; Addressing the Global Threat Through Greater Awareness and Transformative Action> Health Affairs>Vol 33, No 9 .Published September 2014 https://www.healthaffairs.org/doi/10.1377/hlthaff.2014.0383

(8) Hooton,T & Levy,S, Antimicrobial Resistance: A Plan of Action for Community Practice, American Family Physician, Volume 63 Number 6 https://www.aafp.org/afp/2001/0315/p1087.pdf

(9) Hyun, D. Antibiotic Use in Outpatient Settings, published May3, 2016 https://www.pewtrusts.org/en/research-and-analysis/reports/2016/05/antibiotic-use-in-outpatient-settings

(10)George, R & Morris, A, Pro/Con Debate; Should antimicrobial stewardship program be adopted universally in the intensive care unit, Published online 2010, Feb 25 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875495/

(11) https://www.patientadvocate.org/explore-our-resources/understanding-health-insurance/drug-formulary-lists/know-your-drug-formulary-restrictions-prior-authorization/

(12) Cunha,C & Varughese,Antimicrobial Stewardship Prgrams, published online feb 4 2013 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654613/

(13) http://www.astho.org/Programs/Infectious-Disease/Emerging-Infectious-Diseases/Issue-Brief-State-Strategies-to-Address-Antimicrobial-Resistance/

(14) Sciarretta et al.Economic Incentives for Antimicrobial Therapy Development: Summary from the Transatlantic Task Force on Antimicrobial Resistance https://www.cdc.gov/drugresistance/pdf/Economic-Incentives-for-Antimicrobial-Development-TATFAR.pdf

(15)https://www.fda.gov/animalveterinary/guidancecomplianceenforcement/guidanceforindustry/ucm216939.htm

(16) Rivers, K & Steward,H, Initiating an Antimicrobial Stewardship Program: The Costs and the Benefits, published online August 28, 2016 https://www.pharmacytimes.com/news/initiating-an-antimicrobial-stewardship-program-the-costs-and-the-benefits

(17) https://www.fda.gov/NewsEvents/Newsroom/FDAInBrief/ucm595264.htm