America’s Strategy for Combating Antibiotic-Resistant Bacteria

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By Yin Wong, PharmD; Mylinda Dill, PharmD; and Christian Hartman, PharmD, MBA, FSMSO

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Since the initial discovery of penicillin by Sir Alexander Fleming in 1928, a large number of antimicrobial agents have been harnessed for clinical use. While antimicrobial agents eradicate pathogens and control infections, it was recognized early on that bacteria exposed to antibiotics can evolve to survive them, raising concerns for antibiotic resistance. Inappropriate antibiotic use has been recognized as contributing to antimicrobial resistance. According to the Society of Healthcare Epidemiology of America (SHEA, 2012) the past 30 years of antimicrobial use have brought multidrug-resistant pneumococci, gonoccocci, and Salmonella spp. as well as extremely drug-resistant tuberculosis to patients in the community. The Center for Disease Control and Prevention has estimated that antibiotic-resistant organisms are responsible for over 2 million infections and 23,000 deaths annually in the United States (CDC, 2013). The economic impact of antibiotic resistance varies, but may be as high as $20 billion in excess direct healthcare costs and $35 billion due to lost productivity to society (PCAST, 2014).

Attempting to take control of a problem that the healthcare field has been aware of for decades (SHEA, 2012), the Presidential Office of The White House issued Executive Order 13676: Combating Antimicrobial-Resistance Bacteria in September 2014. Subsequently, the President’s Council of Advisors on Science and Technology (PCAST) released a report on combating antibiotic resistance in which it provided recommendations and strategies to promote appropriate antimicrobial use (PCAST, 2014). The National Action Plan for Combating Antibiotic-Resistant Bacteria released in March 2015 provides a five-year action plan that lays out practical steps and milestones for achieving the Executive Order’s goals while addressing the recommendations set forth by the PCAST. The primary goal of this National Action Plan is to guide activities by the federal government as well as actions by public heath, healthcare, and veterinary partners to address this urgent drug-resistant threat.

The National Action Plan for combating antibiotic-resistant bacteria has five major goals (Table 1, pg. 16):
Goal 1: Slow the emergence of resistant bacteria and prevent the spread of resistant infections.
Goal 2: Strengthen national “One-Health” surveillance efforts to combat resistance.
Goal 3: Advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria.
Goal 4: Accelerate basic and applied research and development for new antibiotics, other therapeutics, and vaccines.
Goal 5: Improve international collaboration and capacities for antibiotic-resistant prevention, surveillance, control, and antibiotic research development.

Table 1. The National Action Plan Goals and Objectives (The White House, 2015)

Goal Focus Objectives
Goal 1 Slow the emergence of resistant bacteria and prevent the spread of resistant infections. 1.1 Implement public health programs and reporting policies that advance antibiotic-resistance prevention and foster antibiotic stewardship in healthcare settings and the community .
    1.2 Eliminate the use of medically-important antibiotics for growth promotion in food-producing animals and bring other agricultural uses of antibiotics—for treatment, control, and prevention of disease—under veterinary oversight.
    1.3 Identify and implement measures to foster stewardship of antibiotics in animals.
Goal 2 Strength national One-Health surveillance efforts to combat resistance. 2.1 Create a regional public health laboratory network to strength national capacity to detect resistant bacterial strains and a specimen repository to facilitate development and evaluation of diagnostics tests and treatments.
    2.2 Expand and strengthen the national infrastructure for public health surveillance and data reporting, and provide incentives for timely reporting for antibiotic-resistance and antibiotic use in all healthcare settings.
    2.3 Develop, expand, and maintain capacity in state and federal veterinary and food safety laboratories to conduct antibiotic susceptibility testing and characterize select zoonotic and animal pathogens .
    2.4 Enhance monitoring of antibiotic-resistance patterns, as well as antibiotic sales, usage, and management practices, at multiple points in the production chain for food animals and retail meat.
Goal 3 Advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria. 3.1 Develop and validate new diagnostics, including tests that rapidly distinguish between viral and bacterial pathogens and tests that detect antibiotic-resistance (that can be implemented easily in a wide range of settings).
    3.2 Expand availability and use of diagnostics to improve treatment of antibiotic-resistant infections, enhance infection control, and facilitate outbreak detection and response in healthcare and community settings.
Goal 4 Accelerate basic and applied research and development for new antibiotics, other therapeutics, and vaccines. 4.1 Conduct research to enhance understanding of environmental factors that facilitate the development of antibiotic-resistance and the spread of resistance genes that are common to animals and humans.
    4.2 Increase research focused on understanding the nature of microbial communities, how antibiotics affect them, and how they can be harnessed to prevent disease.
    4.3 Intensify research and development of new therapeutics and vaccines, first-in-class drugs, and new combination therapies for treatment of bacterial infections.
    4.4 Develop non-traditional therapeutics and innovative strategies to minimize outbreaks caused by resistant bacteria in human and animal populations.
    4.5 Expand ongoing efforts to provide key data and materials to support the development of promising antibacterial drug candidates.
Goal 5 Improve international collaboration and capacities for antibiotic-resistant prevention, surveillance, control, and antibiotic research development. Surveillance
5.1 – 5.3 Promote laboratory capability to identify WHO priority antimicrobial resistant pathogens and collaborate with WHO, OIE, and other international efforts focused on the development of integrated, laboratory-based surveillance.
    Research and Development
5.5 Establish and promote international collaboration and public-private partnerships to incentivize development of new therapeutics to counter antibiotic-resistance.
    Prevention and Control
5.6 – 5.8 Support and partner with other nations to develop and implement national plans to combat antibiotic-resistance and promote quality, safety, and efficacy of antibiotics.

 

 

 

 

 

By the year 2020, the implementation of the National Action Plan will reduce the incidence of urgent and serious antibiotic-resistant bacteria threats, which include but are not limited to the following (The White House, 2015):

  1. Reduce the incidence of overall Clostridium difficile infection by 50% compared to 2011 estimates.
  2. Reduce hospital-acquired infections of carbapenems-resistant Enterobacteriaceae (CRE) by 60% compared to estimates.
  3. Maintain the prevalence of ceftriaxone-resistant Neisseria gonorrhoeae below 2% compared to 2013 estimates.

Focus on Antimicrobial Stewardship

Antimicrobial stewardship is defined as a systematic effort to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms, and the emergence of resistance (Dellit et al., 2007). Simply put, it is to use the right antibiotics at the right time at the right dose for the right duration (The White House, 2015). Effective antimicrobial stewardship requires a multidisciplinary team, which includes at a minimum, an infectious diseases physician and a clinical pharmacist with infectious disease training. The inclusion of a clinical microbiologist, an information system specialist, an infection preventionist, and hospital epidemiologist are ideal. This program is designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy, and route of administration. While antibiotic stewardship programs have been shown to reduce the emergence of multidrug resistant organisms, to improve patient outcomes, and to reduce healthcare costs, no national legislative or regulatory mandates are designed to optimize use of antimicrobial therapy through antimicrobial stewardship—with the exception of the state of California (SHEA, 2012).

The National Action Plan Goal 1 concentrates on improving the stewardship of current antibiotic use across all healthcare settings and preventing the spread of drug-resistant pathogens in healthcare facilities and communities (The White House, 2015). By the year 2020, vital stewardship-related outcomes will include the following:

  • Establishing antibiotic stewardship programs in all acute care hospitals and improved antibiotic stewardship across all healthcare settings.
  • Reducing inappropriate antibiotic use by 50% in outpatient settings and by 20% in inpatient settings.

The objectives of Goals 1 and 2 focus on enhancing and creating improved antibiotic usage and resistance pathogen surveillance. The “One-Health” approach to disease surveillance refers to the integration of data from surveillance systems that monitor antibiotic sales, usage, resistance, and management practice for both human and animal pathogens. By the year 2020, significant surveillance-related outcomes will include the following:

  • Establishing Antibiotic Resistance (AR) Prevention (Protect) Programs in all 50 states to monitor regionally important multidrug-resistant organisms and provide feedback and technical assistance to healthcare facilities.
  • Routine reporting of antibiotic use and resistant data to NHSN by 95% Medicare-eligible hospitals, as well as by Department of Defense (DOD) and Veterans Affairs (VA).

Milestones

The National Action Plan for Combating Antibiotic-Resistant Bacteria also includes the following milestones (The White House, 2015):

Within one year:

  • The Departments of HHS, DOD, and VA will review existing regulations and propose new ones to require various healthcare settings to implement robust antibiotic stewardship programs aligned with the CDC Core Elements.
  • The National Healthcare Safety Network (NHSN) will begin tracking the number of healthcare facilities with stewardship policies and programs in place.
  • CDC Emerging Infections Program (EIP) sites will perform assessments of antibiotic use and resistance to allow updating national estimates of antibiotic-resistant, healthcare-associated infections and antibiotic-resistant threats in the United States. The EIP is a network of 10 state health departments: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee.
  • CDC will finalize arrangements for the purchase of proprietary data on inpatient antibiotic use to supplement NHSN data until a larger number of hospitals begin to utilize the NHSN module for antibiotic use reporting.
  • CDC will work with healthcare and public health partners to propose new healthcare-facility antibiotic use measures to the National Quality Forum (NQF).

Within three years:

  • All hospitals that participate in Medicare and Medicaid programs must comply with Conditions of Participation (COP). The Centers for Medicare & Medicaid Service (CMS) will issue new COPs or revise current COP Interpretive Guidelines (IP) to advance compliance with recommendations in CDC’s Core Elements of Hospital Antibiotic Stewardship Programs. HHS, DOD, and VA will also implement policies that:

• Encourage implementation of antibiotic stewardship programs as a condition for receiving federal grants for healthcare delivery (e.g., in community healthcare centers).

• Require health facilities operated by the U.S. government to develop and implement antibiotic stewardship programs and participate in NHSN reporting.

  • All acute care hospitals governed by the CMS COP will implement antibiotic stewardship programs. CMS will expand COP requirements to apply to long-term acute care hospitals, other post-acute facilities, ambulatory surgery centers, and dialysis centers.
  • CMS will revise existing Interpretive Guidelines (IGs), as needed, to include antimicrobial stewardship improvements.
  • At least 25 states, the District of Columbia, and Puerto Rico will establish or enhance antibiotic stewardship activities in inpatient healthcare delivery settings, in accordance with the CDC Core Elements. CDC will support these efforts via State AR Prevention (Protect) Programs for Healthcare.
  • CDC will provide technical assistance to federal facilities and other large health systems in scaling up implementation and assessment of interventions to improve outpatient antibiotic prescribing, extending effective interventions to long-term care settings, and ensuring long-term sustainability of antibiotic stewardship efforts.
  • CDC, CMS, and partners will propose expanded quality measures for antibiotic prescribing.
  • CMS will expand the Physician Quality Reporting System (PQRS) to include quality measures that discourage inappropriate antibiotic use to treat non-bacterial infections.
  • CDC will use data collected through the NHSN antibiotic use (AU) module to provide annual national estimates of aggregated inpatient AU and feedback to healthcare facilities on antibiotic use, indicating whether antibiotic use rates are above or below the national average.
  • CDC will establish routine reporting of antibiotic use and resistance data from select hospital systems via the NHSN, AU, and AR modules.
  • Starting in 2016, CDC will issue yearly reports on progress in meeting the national target of 50% reduction in inappropriate use of antibiotics in outpatient settings, as well as on overall trends in antibiotic prescribing.
  • CDC Emerging Infections Program sites will perform assessments of antibiotic use and resistance to allow updating of national estimates of antibiotic-resistant, healthcare-associated infections, and of antibiotic-resistance threats in the United States.

Table 2. Clinical Resources for Development of Antimicrobial Stewardship Programs

Organization Internet Address
The California Antimicrobial Program Stewardship Initiative http://www.cdph.ca.gov/programs/hai/Pages/AntimicrobialStewardshipProgramInitiative.aspx
Centers for Disease Control and Prevention—Core Elements for Hospital Antibiotic Stewardship Program Recommendations http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html
Wolters Kluwer Health—Antimicrobial Stewardship Guidelines www.clinicalonesource.com
American Society of Hospital Pharmacists—Implementing Antimicrobial Stewardship Programs in Health Systems: An Interprofessional Team Approach http://www.leadstewardship.org/
Society for Healthcare Epidemiology of America (SHEA) http://www.shea-online.org/PriorityTopics/AntimicrobialStewardship.aspx
American Hospital Association (AHA) http://www.ahaphysicianforum.org/resources/appropriate-use/antimicrobial/index.shtml
Infectious Diseases Society of America (IDSA) http://www.idsociety.org/stewardship_policy/

 

 

 

 

 

 

 

 

The National Directive on Antimicrobial Stewardship

California has been a pioneer in the development of antimicrobial stewardship programs. In 2006, California Senate Bill (CB) 739 established the California Department of Public Health (CDPH) Healthcare-Associated Infections (HAIs) program to conduct surveillance, prevention, and reporting of HAIs in acute care hospitals statewide (Trivedi et al., 2013). California SB 739 requires acute care facilities to develop a review process to evaluate the antibiotic use and monitor results through appropriate quality improvement committees. In a statewide survey, Trivedi and Rosenberg (2013) found that 50% of acute care hospitals in California had an established ASP and 30% reported planning an ASP. Community hospitals represented 73% of the survey respondents. This study demonstrated that many ASPs exist in California, particularly in community settings where resources were thought to be scarce. Leaders in California have demonstrated that legislative or regulatory mandates to promote judicious use of antimicrobial stewardship programs can lead to great success.

In response to the Executive Order 13676 and the PCAST report recommendations, the National Action Plan also calls for a national mandate for the establishment of an antimicrobial stewardship program (ASP) at all acute care hospitals. This requirement will apply to long-term acute care hospitals, other post-acute facilities, ambulatory surgery centers, and dialysis centers. Historically, dedicated antimicrobial stewardship programs have been associated with academic medical centers; with the upcoming CMS COP incentives, the development of antimicrobial stewardship programs are expected to increase broadly. While the CMS COP incentive will take effect within the next three years, the Nation Action Plan references CDC Core Elements of Hospitals Antimicrobial Stewardship Programs and states that antibiotic stewardship programs shall align with those core elements. Hospitals administration and healthcare providers should acquaint themselves with the core elements of ASP and begin assessing their institutions’ antimicrobial use and related policies and procedures now.

Hospitals and Healthcare Providers: Moving Forward

Reporting antimicrobial-resistant pathogens has always been part of infection control’s responsibility. Section 501(b) of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 authorized CMS to reimburse hospitals that successfully report specific quality measures as part of their reimbursement rates. Hospitals are thus required to report the following HAIs on a routine basis: central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), Clostridium difficile (C.diff) infection rate, methicillin-resistant Staphylococcus aureus (MRSA) infection rate, and surgical site infections (SSI) for colon surgery and abdominal hysterectomy. These metrics are consistently reported in the National Healthcare Safety Network (NHSN) as part of COP.

The national action plan will expand reporting efforts to include outcomes associated with antibiotic utilization and resistance as well as antimicrobial stewardship program initiatives. Healthcare organizations across the United States will need to provide dedicated clinical, quality, and technical resources to address the impending reporting requirements and programmatic development for comprehensive antimicrobial stewardship programs. This national action plan represents an aggressive policy to curb antibiotic resistance and provides specific steps for healthcare organizations to create comprehensive programs. Hospital administrators and executives will need to provide adequate resources to build infrastructure to combat antibiotic resistance and address the intent of the National Action Plan. Despite the fact that the CMS COP standards on implementation of ASP and development of the NHSN AUR module have yet to be released, hospital administrators and healthcare providers can start by getting an understanding of the core elements that comprise an ASP.

According to the CDC (2014), an antimicrobial stewardship program encompasses the following core elements:

  • Leadership commitment. Critical to the success of ASP, formal initiation of the program with leadership to provide financial, training, or informational technology (IT) support.
  • Accountability. Identify a single physician and pharmacy leader who will be responsible for program outcomes.
  • Drug expertise. Appoint a single pharmacist leader responsible for working to improve antibiotic use.
  • Action. Implement ≥1 recommended action (i.e. policies that support optimal antibiotic use, restricted antibiotics, automatic changes from intravenous to oral antibiotic therapy, etc.).
  • Tracking. Monitor antibiotic prescribing and resistance (i.e. antibiotic use process measures, antibiotic usage, patient outcomes measures, etc.).
  • Reporting. Regular reporting and information dissemination on antibiotic prescribing and resistance to local stakeholders.
  • Education. Provide education to clinicians about resistance and optimal prescribing.

Professional organizations are increasingly providing resources to help healthcare systems create ASPs (Table 2). We urge hospital administration and executives to meet with local stakeholders (pharmacists, infection control/epidemiologists, microbiologists, and informatics specialists) to evaluate the current antimicrobial stewardship and antibiotic resistance reporting efforts at your institutions. The CDC’s Core Elements of Hospital Antibiotic Stewardship Programs provides a checklist that can be used for hospitals to systematically assess if the principles and actions to improve antibiotic use are in place. An institution-specific project plan needs to be created with local stakeholders to prepare for the coming requirements of the national mandate.

Conclusion

Healthcare providers and patients have been battling antibiotic resistance ever since the recognition of methicillin resistant Staphylococcus aureus in 1961, yet, there have been no legislative or national initiatives to combat the ongoing antibiotic resistance. The September 2014 Presidential Executive Order and subsequent PCAST report as well as the recent National Action Plan represent revolutionary steps toward combating antibiotic resistance. More information on CMS regulatory standards for the establishment of an ASP and NHSN mandatory AUR reporting have yet to be released, but awareness for antimicrobial stewardship has now been raised as a result of the Executive Order and the PCAST report.

Yin Wong is a health information and clinical outcomes research fellow for Wolters Kluwer Health and a graduate of Massachusetts College of Pharmacy and Health Sciences. After graduation, she completed a PGY1 pharmacy practice residency at Massachusetts General Hospital. Wong may be reached at yin.wong@wolterskluwer.com.

Mylinda Dill is a health information and clinical outcomes research fellow for Wolters Kluwer Health. She is a graduate of Harding University College of Pharmacy. Dill may be reached at mylinda.dill@wolterskluwer.com.

Christian Hartman is a senior director of clinical research, content development and professional services at Wolters Kluwer Health. He is a member of the Wolters Kluwer Health Clinical Solutions Innovation Lab (iLab). He founded and served as president of the Medication Safety Officers Society, a professional organization under the Institute for Safe Medication Practices (ISMP), representing medication safety officers at healthcare organizations. He is an assistant professor of medicine and nursing at the University of Massachusetts Medical School, adjunct assistant professor of pharmacy practice at the Massachusetts College of Pharmacy and Health Sciences, adjunct assistant professor of pharmacy practice at the University of Rhode Island, and clinical assistant professor of pharmacy practice at Northeastern University. Hartman is a World Health Organization (WHO) expert. He may be reached at christian.hartman@wolterskluwer.com.

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Center for Disease Control and Prevention. (2015). Antimicrobial Use and Resistant (AUR) Module. Center for Disease Control and Prevention. Retrieved from http://www.cdc.gov/nhsn/PDFs/pscManual/11pscAURcurrent.pdf

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Trivedi, K.K., & Rosenberg, J. (2013). The state of antimicrobial stewardship programs in California. Infection Control and Hospital Epidemiology, 34(4): 379-384.

The White House. (2015). National Action Plan for Combating Antibiotic-Resistant
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