The federal plan to combat and prevent highly resistant bacteria anticipates a stronger role for diagnostic testing and laboratory surveillance
By Elaine Sanchez Wilson
Responding to the rise in antibiotic-resistant infections, and their associated economic and health costs, the Administration announced its National Strategy on Combating Antibiotic-Resistant Bacteria last September. Issuing an executive order, President Obama called for collaboration among experts in academia, industry, and government, representing such fields as healthcare, public health, veterinary medicine, agriculture, and food safety. To bolster their efforts, Obama introduced a fiscal year (FY) 2016 budget that nearly doubles the amount of federal funding for combating and preventing antibiotic resistance to more than $1.2 billion.
The fight is an arduous one. Highly resistant bacterial infections account for an estimated 23,000 deaths and 2 million illnesses in the United States each year, according to the US Centers for Disease Control and Prevention (CDC).1 While estimates of the economic impact of antibiotic-resistant infections vary, they have ranged to as much as $35 billion in lost productivity from hospitalizations and sick days, and as high as $20 billion annually in excess direct healthcare costs.2 The Administration’s battle plan is a 5-year, multilevel approach that outlines five interrelated goals:
- Prevent and contain outbreaks of antibiotic-resistant infections
- Identify and report cases of antibiotic resistance
- Advance the development and use of rapid diagnostic tests for the identification and characterization of antibiotic-resistant bacteria
- Accelerate the research and development of new antibiotics, therapeutics, and vaccines
- And improve international collaboration and capacities for antibiotic-resistance prevention, surveillance, and control.3
If Congress votes to provide the necessary funding, clinical laboratories will play an integral role in contributing to the strategy’s success. The plan includes a proposed regional public health network, called the Detect Network of Antibiotic Resistance Regional Laboratories, which will provide antimicrobial resistance testing to help fill the gap between data generated at hospitals and data needed for prevention efforts.
“We envision a network that would have the kind of antimicrobial susceptibility testing and resistance testing that we have at CDC,” says Jean Patel, PhD, deputy director of the Office of Antimicrobial Resistance at CDC. “Clinical labs are generating very important antimicrobial susceptibility data to guide treatment decisions in patients. They will continue to do this, and we want their testing to be robust.”
A PUBLIC HEALTH APPROACH
Patel points out that clinical labs are focused on collecting data for patient care. Additional data, like identifying resistance mechanisms, are not always necessary for patient care; as a result, they are not routinely collected in most labs. Nevertheless, these labs have the ability to identify most but not all types of antibiotic resistance, especially novel forms of resistance. “There is often a gap between what a clinical laboratory can produce and the kind of data that we need for public health decisions,” she continues. “Sometimes the hospital laboratory will do tests for mechanisms of resistance, but if they don’t actually need that information for managing a patient, then they might not collect that information. In that case, it’d be a cost that they don’t really need for what their specific task is, which is to get the patient better.
“We need this kind of information for infection control and for prevention decisions,” Patel adds. “The kind of information we need for public health decisions and prevention activities for some of our most resistant pathogens are what types of resistant mechanisms are present, and also, whether the isolates might be part of an outbreak.”
CDC’s proposed Detect Network aims to serve as a national resource to characterize emerging resistance and rapidly identify outbreaks of antibiotic-resistant organisms. Member laboratories would be expected to utilize state-of-the-art methods to characterize known resistance patterns in real time and more quickly identify clusters of resistant organisms.
Not only contributing to the country’s overall disease surveillance knowledge, the Detect Network could also serve to boost the efforts of the global “One-Health” initiative. This international campaign looks to expand interdisciplinary collaboration and communications in all aspects of healthcare for humans, animals, and the environment, around the world.
According to Scott K. Fridkin, MD, senior advisor for antibiotic resistance in healthcare in CDC’s Division of Healthcare Quality Promotion, disease surveillance networks in different countries historically communicated only on a periodic basis, as needed. “More recently, regular communication has begun as attempts have been made to standardize definitions, testing approaches, and reporting approaches,” Fridkin says, pointing to efforts like the Transatlantic Task Force on Antimicrobial Resistance between the United States and European Union.
Internationally, approaches to antibiotic resistance surveillance vary, notes Fridkin. “Countries have a variety of surveillance networks to fit their needs and available resources. Many countries rely on sentinel site surveillance, that is, they use a sample of laboratories that report routine testing results to a central agency or reference lab. Some countries rely on routine submission of a sample of clinical isolates for reference testing at a centralized laboratory. Many rely on a hybrid system combining aspects of both of these. Most critical is activity to ensure the timely and accurate testing of clinical isolates, reporting of results to clinicians to help direct optimal therapy, and communication with central public health agencies regarding isolates of public health concern.”
Mark Miller, MD, FRCPC, chief medical officer at bioMérieux, stresses the critical need in the United States and around the globe for the surveillance of antimicrobial resistance. “A system that collects, qualifies, and quantifies resistance trends as they happen in real time would represent an enormous leap forward in our battle against antibiotic resistance,” Miller says. “With this information, partnering organizations could detect emerging epidemic patterns and take steps to mitigate these outbreaks; hospitals could use this real-time data to inform clinicians about better empiric antibiotic selection; and countries could create a sentinel alert network informing them where novel antibiotic resistance mechanisms have recently emerged.”
For some enteric pathogens, such as salmonella, antimicrobial therapy isn’t always indicated. In those cases, because the physician would not prescribe antimicrobial therapy, a laboratory would not perform the testing. “We’d want to test those isolates for resistance because that helps us track resistance that might be coming from a food-producing animal to humans,” Patel says. “That kind of resistance data is needed for public health decisions.”
Through the regional lab network, CDC and its public health partners hope to accumulate real-time, actionable information about dangerous antibiotic resistant threats. “If we built this lab network, more salmonella isolates can be tested a public health laboratory,” Patel says.
Additionally, CDC looks to enhance its Antibiotic Resistance Isolate Bank, which would provide a complete collection of current antibiotic-resistant bacteria. Under the plan, CDC and regional antibiotic resistance labs would send samples and data to the isolate bank. Industry and academic institutions could then use samples to test new antibiotic agents and help patients receive earlier diagnosis and effective treatment. The isolate bank could assist laboratorians in keeping pace with ever-evolving mutations, and help guide FDA approval of new tests, antibiotics, and related products. “It should represent among the most resistant isolates that are occurring in hospitals. We want to make sure that that resource is available to other groups that need it to develop new diagnostic tests for new drugs,” Patel says.
Patel notes that the process of setting up a bank is already underway, as part of a joint effort between CDC and FDA. Called the FDA-CDC Antimicrobial Resistance Isolate Bank, the bank includes a few of the most resistant Gram negative bacterial pathogens that currently exist. “We’ve had a robust interest in isolates in that bank, so we think this is a really important resource for industry,” Patel says. “Industry can place an order for the isolates in the bank. We’re over 40 orders, and we’re adding isolates to that bank every day.”
With its Vitek 2 system representing the largest global installed base of laboratory equipment for the automated standardized antibiotic susceptibility testing of bacteria, bioMérieux believes it is uniquely positioned to assist in establishing a laboratory-based surveillance network for antibiotic-resistant organisms. To meet that end, the company has reached out to various governmental and nongovernmental agencies, including CDC, about its desire to use Vitek 2 to provide real-time antimicrobial resistance data within a comprehensive surveillance system.
Specifically, bioMérieux is looking to connect its lab equipment to provide real-time data in two phases: first, to establish connectivity in the United States, and then ultimately worldwide. “In phase 1, antibiotic resistance surveillance data would be available at the local level, in participating hospitals and healthcare facilities, state wide, in departments of health, and nationally, at CDC,” Miller says. “In phase 2, the data would also be available to participating countries and regions globally to form the world’s largest antibiotic resistance surveillance database.”
Miller says the connectivity project aims to achieve four key objectives:
- Surveillance in real-time of antibiotic resistance patterns for all classes of organisms tested on the comprehensive Vitek 2 automated antimicrobial susceptibility test system, thereby allowing the rapid detection of emerging or epidemic patterns
- Better empiric antibiotic selection based on surveillance data
- Early detection of novel antibiotic resistance mechanisms
- Provision of strains to research collaborators and the pharmaceutical industry for studying resistance mechanisms.
“However, there are many obstacles to overcome in order to make this type of surveillance system a reality, including controversy over ownership of the data, patient data privacy protection, and the interfaces needed to interconnect the multitude of software programs within the various laboratory information systems,” Miller says. “We continue to believe that this type of network is possible and would represent a monumental improvement in public health, but to make it a reality within the United States would require a concerted effort with the CDC, the American Hospital Association, state and federal public health officials and, most likely, legislative support.”
STATE OF AFFAIRS
Data produced by Detect Network laboratories would not only be pertinent for the public health realm. “They’ll be important for the state public health department where the infection originated,” Patel says. “They’ll be important for CDC, and they’ll be important for the hospital that submitted the isolate to the network. We want to make sure that the network that we build has ability to communicate results to all of those groups.”
Patel envisions that the kinds of data produced in the network would be used to make prevention decisions on an institutional and regional basis. For example, data could be tied to the state prevention programs proposed in the President’s FY16 budget. Although no full-scale state prevention programs are in place at this time, the national strategy includes a goal to have all 50 states monitoring regionally important multidrug resistant organisms and providing feedback and technical assistance to healthcare facilities.
“If we see similar isolates occurring in hospitals that are within the network and they’re sharing patients, then that knowledge should be transmitted to the state prevention programs and allow them to intervene and prevent transmission in a more strategic way,” Patel says.
A reliable, real-time network would have significant positive patient outcomes, Miller agrees. “It would allow the rapid detection of emerging resistant pathogens or epidemic patterns of drug-resistant bacterial transmission,” he says. “It would contribute to better empiric antibiotic selection based on the surveillance data, it would facilitate early detection of novel antibiotic resistance mechanisms; and it would provide resistant bacterial strains to research collaborators and the pharmaceutical industry for studying resistance mechanisms, thereby supporting the development of new antibiotics.”
As Congress considers the FY16 budget, CDC continues internal discussions regarding how to move forward in implementing the network. In the meantime, CDC is developing an implementation plan, which includes developing a list of characteristics of member Detect laboratories.
“We are planning to build capacity using a tiered process that will begin with testing, which can provide the greatest impact,” Patel says. “If we receive funding from Congress for this initiative, we anticipate issuing requests for proposals and funding recipients within the first year.”
Elaine Sanchez Wilson is associate editor for CLP. For further information, contact CLP chief editor Steve Halasey via [email protected].
- Antibiotic/antimicrobial resistance: the problem [online]. Atlanta: US Centers for Disease Control and Prevention, 2015. Available at: http://www.cdc.gov/drugresistance/solutions-initiative/the_problem.html. Accessed September 28, 2015.
- Fact sheet: Obama administration releases national action plan to combat antibiotic-resistant bacteria [online]. Washington: The White House Office of the Press Secretary, 2015. Available at: https://www.whitehouse.gov/the-press-office/2015/03/27/fact-sheet-obama-administration-releases-national-action-plan-combat-ant. Accessed September 28, 2015.
- Antibiotic resistance solutions initiative: $264M, a comprehensive response [online]. Atlanta: US Centers for Disease Control and Prevention, 2015. Available at: http://www.cdc.gov/drugresistance/pdf/ar-solutions-initiative-fact-sheet.pdf. Accessed September 28, 2015.