Newsletter Vol. 29 No. 3

GAIN Act introduced in U.S. Senate
Government Accountability Report finds that agencies have made insufficient progress
Transatlantic Taskforce on Antimicrobial Resistance outlines 17 recommendations for U.S./EU collaboration

GAIN Act introduced in U.S. Senate

After its introduction in the House of Representatives by Phil Gingrey (R-GA) and Diana DeGette (D-CO), the Generating Antibiotic Incentives Now (GAIN) Act was brought forward in the Senate on October 19, 2911. This legislation will help increase the commercial value of new antibiotic drugs for the treatment of drug-resistant bacteria and streamline the regulatory process so that innovative antibiotics can reach the public sooner.

The GAIN Act was sponsored by Senator Bob Corker (R-TN) and Senator Richard Blumenthal (D-CT). Additional co-sponsors include Senators Michael Bennet (D-CO), Chris Coons (D-DE), Orrin Hatch (R-UT), Pat Roberts (R-KS), Bob Casey (D-PA), and Lamar Alexander (R-TN). The bill has been endorsed by 49 groups, including St. Jude Children’s Research Hospital, Le Bonheur Children’s Hospital, University of Tennessee Health Sciences Center, East Tennessee State University Quillen College of Medicine, the Regional Medical Center at Memphis (MED), the National Military Vets Alliance, the American Medical Association, and Children’s National Medical Center. Read expert opinions about the introduction of this legislation in the APUA Clinical Newsletter Vol.29 No.2. (Back to top)


GAO report finds that agencies have made limited progress

The September 2011 report of the Government Accountability Office entitled “Antibiotic Resistance: Agencies Have Made Limited Progress Addressing Antibiotic Use in Animals” examined work done by two government agencies (the Department of Health and Human Services and the U.S. Department of Agriculture) since 2004 – the data they collected on antibiotic use and resistance in food animals, the actions they took to mitigate the risk of antibiotic resistance in humans as a result of antibiotic use in animals, and the research the agencies did to pursue alternatives to antibiotics in preserving animal health. The GAO also reviewed the actions taken during this time by the EU as a whole, and Denmark in particular, to regulate antibiotic use in food animals and compared it to work done in the U.S.

The GAO found that while the HHS and USDA do collect data from pharmaceutical companies on drug sales, the data lack crucial details needed to extrapolate antibiotic use trends. For example, although bulk sales data can be obtained, the data do not show what species the antibiotics were administered to, or their intended use (e.g. disease treatment, disease prevention, growth promotion, etc.). Bacterial samples taken from food animals, retail meat, and industry personnel are also not collected regularly enough (some samples are only collected every 5-6 years) to show the presence and progression of antibiotic resistance over time, and is only representative of a handful of states rather than of the U.S. as a whole. Both antibiotic use data and antibiotic resistance data must be collected often and thoroughly in order to understand the relationship between degree of use and emergence of resistant bacteria in animal and human populations.

Since 2003, with the issuance of Guidance #152 (“Evaluating safety of antimicrobial new animal drugs with regard to their microbiological effects on bacteria of human health concern”), the FDA has been regulating the use of antibiotics critically important to human medicine. If the drug treats foodborne illness and is one of only a few alternatives in treating a disease, it may not be used in ways that might jeopardize its effectiveness for human health, and the drug can be removed from the market by the FDA if that seems to be the case. However, most antibiotics being used in food animal production today were developed before 2003, and the process of removing any of them from the market is long and expensive. The FDA instead relies on pharmaceutical companies to voluntarily phase out growth promotion as official uses of their drugs and to change their approval for sale from over-the-counter to veterinary feed directive (VFD). However, the FDA and HHS do not have a timeline for the phasing out of these antibiotics in food animal production, nor do they have metrics to measure their progress.

The GAO also noted that the HHS and USDA both claim to have taken steps to promote research into alternatives to antibiotics – however, they do not collect data to assess the effectiveness of these steps. Government agencies must provide funding and incentives for researching alternatives (such as vaccines), and must continually assess past research endeavors so that future efforts can be targeted more effectively to fill in any gaps. The HHS and USDA have also ended almost all federal education programs on antibiotic resistance.

Compared to the lagging U.S., the EU has raced ahead in banning the use of any antibiotic as a growth promoter. Denmark instituted this ban in 2000, followed by the entire EU in 2006. Denmark has also increased government oversight of veterinarians and food animal producers, setting limits on antibiotic use on farms and punishing any exceeding of the limits with additional monitoring, which the offending farm must pay for. Medically important drugs are banned for animal use except as drugs of last resort, and even then must be reported to regulatory officials when used. In turn, Denmark has also witnessed dramatic results. Salmonella has been eradicated in Denmark, antibiotic use fell 25% from 2010 to 2011, and levels of resistant Enterococcus (in humans) and Campylobacter (in animals) fell at the same time. Throughout all this, there was no corresponding increase in foodborne pathogens in retail meat. Policymakers in the EU attribute their successes to sustained consumer interest in the issue of antibiotic resistance, constant tracking of both use data (going beyond merely tracking bulk sales data) and resistance data, and policy making based on the precautionary principle (where there is a threat of serious or irreversible damage, lack of certainty should not postpone cost-effective measures to reduce risk to human health).

Taking these evaluations into consideration, the GAO recommends that the HHS and FDA 1) collect more detailed and more nationally representative data to track the effectiveness of policies that may curb antibiotic resistance, 2) enhance surveillance of antibiotic resistant bacteria in food animals, and 3) focus federal research efforts more effectively on finding alternatives to antibiotic use. Read the full GAO report from September 2011 here. (Back to top)

Transatlantic report outlines 17 recommendations for U.S./EU collaboration

The Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) was established in 2009 at the summit of the U.S. and EU presidencies, in response to the growing public health danger of antibiotic resistance and the scarcity of new drugs in the development pipeline. These simultaneous threats have led to a rise in the incidence of multi-drug resistant infections, especially in healthcare settings and in patient populations such as the elderly, the immunocompromised (as a result of HIV/AIDS, cancer, or other long illness), children, and premature infants.

In 2009, the TATFAR was charged with identifying ways that the U.S. and the EU could cooperate to address urgent issues that contribute to antibiotic resistance in three areas: 1) using antibiotics appropriately in human and veterinary medicine, 2) preventing healthcare-acquired and community-acquired infections, and 3) facilitating the development of new antibiotics. After multiple consultations with stakeholders and with the public, in September 2011 the TATFAR released their first report "Recommendations for Future Collaboration between the U.S. and the EU," containing 17 recommendations that could be implemented in the next two years.

The TATFAR came up with six recommendations pertaining to the appropriate therapeutic use of antibiotics in human and veterinary medicine. The group noted that over half of all antibiotics used in hospitals in the U.S. and the EU are prescribed unnecessarily or inappropriately, and that over half the population sampled in Europe in 2009 was fundamentally misinformed about antibiotic use (believing that antibiotics are effective against viral infections, cold, flu, etc.). These mistaken views contribute to antibiotic misuse in human healthcare and in food animal production, and the TATFAR also recognized that even when guidelines for appropriate antibiotic use are in place (antibiotic stewardship), they must develop a set of common metrics that allow guidelines to be compared between institutions and countries for evaluation and improvement. The following recommendations were made to address appropriate antibiotic use:

  • Develop a common structure and set of progress indicators for hospital antibiotic stewardship programs
  • Establish a U.S./EU working group to measure antibiotic use in hospital settings
  • Collect detailed data on the sales and use of antibiotics in food animals
  • Implement the “Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance” from the Codex Alimentarius
  • Share information on ways to promote appropriate antibiotic use in the veterinary community
  • Establish a U.S./EU working group to assess the effectiveness of communications tools in promoting behavioral change to increase appropriate antibiotic use

The TATFAR also came up with five recommendations for preventing drug-resistant hospital-acquired and community-acquired infections. Almost all of the healthcare-associated pathogens have developed some degree of antibiotic resistance. The TATFAR’s recommendations in this area emphasized the importance of effective infection control measures and surveillance to identify reservoirs of antibiotic resistance:

  • Create a point prevalence survey for healthcare-acquired infections
  • Facilitate communication between the U.S. and the EU about new resistance trends
  • Standardize the susceptibility reporting of bacterial isolates obtained through surveillance programs in the U.S. and the EU
  • Convene public health experts to develop evaluation tools for hospital infection control programs
  • Develop strategies to facilitate vaccine development for healthcare-acquired infections

The third issue, facilitating the development of new antibiotic drugs, is most hampered by the long development period (5-10 years) required to generate and perform clinical testing on a drug. The process of clinical testing on human subjects is itself extremely difficult due to the rapid progression of most bacterial diseases. The TATFAR came up with six recommendations to provide incentives for drug developers and speed the process of regulatory approval and clinical testing:

  • Establish significant “push” incentives (e.g. more funding) and significant “pull” incentives (e.g. longer patent terms) for antibiotic drugs
  • Increase communication between U.S. and EU research agencies to identify opportunities for collaboration
  • Publicize funding opportunities between the U.S. and the EU
  • Facilitate the use of clinical development programs that satisfy regulatory guidelines in both the U.S and the EU
  • Discuss common issues in antibiotic drug development and regulation in the U.S. and the EU
  • Encourage information exchange on drug development, especially for resistant infections and bacterial diseases with limited treatment options.

Read the full Transatlantic Taskforce Report from September 2011 here. (Back to top)

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