United Nations: Superbugs a serious threat to human health, food supply

The Heads of States of the United Nations (UN) recently came together to recognize and commit to combating the threats posed by superbugs. Antimicrobial resistance (AMR)–a broader term than antibiotic resistance–includes bacteria, viruses, parasites, and fungi that develop resistance against medicines that were previously able to cure them. Secretary-General Ban Ki-moon said AMR poses “a fundamental, long-term threat to human health, sustainable food production and development.” At the High-Level Meeting on Antimicrobial Resistance, the UN sought to get and keep strong commitments to address AMR from national, regional, and international political groups.

Global action plan

Last year, the UN World Health Organization (WHO) published the Global Action Plan on Antimicrobial Resistance. The action plan outlines five objectives:

  • to improve awareness and understanding of AMR through effective communication, education, and training;
  • to strengthen the knowledge and evidence base through surveillance and research;
  • to reduce the incidence of infection through effective sanitation, hygiene, and infection prevention measures;
  • to optimize the use of antimicrobial medicines in human and animal health; and
  • to develop the economic case for sustainable investment that takes account of the needs of all countries and to increase investment in new medicines, diagnostic tools, vaccines, and other interventions.

The High-Level Meeting built on and emphasized the importance of achieving the action plan’s objectives.

FAO action plan

In advance of the High-Level Meeting, the Food and Agricultural Organization of the UN (FAO) pledged to help countries develop strategies for tackling the spread of AMR in their food supply chains. It released its own action plan to address AMR specifically in food and agriculture:

  • improving awareness of AMR issues among farmers and producers, veterinary professionals and authorities, policymakers, and food consumers;
  • building national capacities for surveillance and monitoring of AMR and antimicrobial use (AMU) in food and agriculture;
  • strengthening governance related to AMU and AMR in food and agriculture; and
  • promoting good practices in food and agricultural systems and the prudent use of antimicrobials.

Threat of AMR

According to the UN, AMR poses a huge threat. WHO Assistant Director-General and Special Representative for AMR Keiji Fukuda explained how deadly AMR is to humans: “By 2050, estimates indicate more people could die from antibiotic resistant infections than those who currently from cancer. . . . almost 10 million people would die from infections because they couldn’t be treated anymore.” Another effect on human life is less direct, but no less of a threat. Fukuda said that sustainable food supplies–and the availability of food for the growing global population–depend heavily on antibiotics used to treat sick animals and to prevent the spread of diseases.

Andrew Gurman, M.D., President of the American Medical Association (AMA), applauded the UN’s declaration of AMR as a danger. He said, “The AMA will continue to do its part to educate physicians on the importance of antibiotic stewardship in the inpatient and outpatient settings and provide them with the latest tools to help alleviate uncertainty when prescribing antibiotics.”

U.S., U.K. entities form partnership to combat superbugs

An international partnership hopes to speed ahead of the superbug problem as the U.S. and the United Kingdom combine resources to search for new antimicrobial solutions to drug resistance. HHS, the Welcome Trust of London, the AMR Centre of Alderley Park (located in the United Kingdom), and the Boston University School of Law have entered into a cooperative agreement to promote innovation.

CARB-X

The global innovation project, known as the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), represents a public-private partnership that hopes to develop antibiotics and quickly move them through the preclinical testing phase. Once antibiotics reach the human trial phase, private investors may be more motivated to back the projects. The teams hope to have a minimum of two drugs in the clinical phase in five years. CARB-X’s headquarters will be located at the Boston University School of Law and led by an executive team.

Parties

The project will be overseen by the Biomedical Advanced Research and Development Authority (BARDA), the National Institute of Allergy and Infectious Diseases (NIAID), the Welcome Trust and the AMR Centre. The Massachusetts Biotechnology Council and the California Life Sciences Institute will support early-stage projects. RTI International, located in North Carolina, and the Broad Institute of the Massachusetts Institute of Technology and Harvard University will also partner with CARB-X. BARDA will provide $30 million in funding for the first year, and the AMR Centre hopes to provide $14 million. Additional funding from both sources may be provided over five years.

Companies interested in receiving sub-awards for promising projects may submit applications, which will be reviewed beginning in September 2016.

Calling duodenoscope deaths ‘Preventable Tragedies,’ Senate committee demands reform

Contaminated duodenoscopes sickened at least 250 people worldwide between 2012 and Spring 2015, and the Senate’s Health, Education, Labor, and Pensions Committee deemed the illnesses and resulting deaths preventable tragedies. The Committee’s investigation into the outbreaks revealed wrongdoing and/or errors committed by device manufacturers, hospitals, and the FDA that led to a lengthy investigative process, during which additional patients were infected (see Olympus pressed for information about response to superbug outbreaks, Health Law Daily, June 11, 2015). In a January 13, 2016 report, the Committee, led by Ranking Minority Member Patty Murray (D-Wash), made several recommendations for preventing infections related to medical devices, including the implementation of a robust medical device safety surveillance system similar to the existing Sentinel system that monitors drugs.

Flawed investigation

In September 2013, the Centers for Disease Control and Prevention (CDC) notified the FDA of an outbreak of infections at a Chicago-area hospital linked to a duodenoscope manufactured by Hoya Corporation PENTAX Life Care Division (Pentax). Around the same time, a Seattle hospital linked infections to a duodenoscope manufactured by Olympus Medical Systems (Olympus). The hospitals at issue had cleaned the duodenoscopes pursuant to manufacturer instructions. Although the FDA began investigating closed channel duodenoscopes, devices used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at that time, the Committee noted that the FDA did not issue a safety alert to hospitals for at least 17 months. Further,the agency did not provide hospitals with additional measures to supplement reprocessing of duodenoscopes for reuse for nearly two years, during which at least 68 patients were infected in the U.S.

Manufacturer failure

The Committee determined that Olympus failed to issue safety alerts, despite knowledge of potential infection for years; that, Olympus and Fujifilm Medical Systems (Fujifilm) never applied for FDA clearance for their new device designs before selling them in the U.S.; and that Olympus, Fujifilm, and PENTAX attested that their cleaning instructions worked reliably, without sufficient data (see Cracking down: FDA sends warning letters to duodenoscope manufacturers, Health Law Daily, August 18, 2015). It concluded that the duodenoscope manufacturers, along with Custom Ultrasonics, the manufacturer of an automated cleaning machine used on duodenoscopes, “failed at every level to meet basic expectations of transparency and openness.” It further found that 16 U.S. hospitals affected were slow to report infections to various entities and did not follow all steps to report adverse events resulting from the devices to manufacturers and the FDA.

Recommendations

The Committee was most concerned about the length of the FDA’s investigation and its failure to take notice of existing studies from Europe that determined that the duodenoscopes could cause infections, even after adherence to cleaning instructions provided by the manufacturers. As a result, it recommended the creation and implementation of a robust medical device safety surveillance system, similar to the Sentinel system that allows the FDA to monitor drugs. Such a system would allow the FDA to access real-time information on adverse events, such as that included in insurance claims, without relying on manufacturers and hospitals to report them. It would also provide a larger pool of data so that the agency could analyze adverse events in the context of total patients treated.

The Committee specifically recommended that the FDA evaluate the design of closed-channel duodenoscopes and implement a phased recall; update guidance to specify when manufacturers should request 510(k) clearance after devices are modified; and implement new draft guidance to quickly provide providers with information when it becomes aware that a medical device might compromise patient safety. It recommended that Congress require that unique device identifiers (UDIs) be used in insurance claims, electronic health records, and device registries and clarify the FDA’s authority to consider 510(k) applications incomplete due to lack of sufficient data regarding whether a device can be safely cleaned and reused. Finally, it recommended that hospital compliance with adverse event reporting be made a condition of participation in Medicare.