Apr 7, 2011 (CIDRAP News) Warning that medical procedures such as surgery and chemotherapy will become impossible if current trends continue, the Infectious Diseases Society of America (IDSA) today called for a many-pronged campaign to counter the ever-growing threat of antimicrobial resistance.
At a press conference held on World Health Day, IDSA leaders released a set of nine recommendations for attacking the problem, including creating incentives for antibiotic research and development and taxing wholesale antibiotic sales to help pay for development of new drugs.
"The way we've managed our antibiotics for the past 70 years has failed," IDSA President James M. Hughes, MD, said in a press release. "Antibiotics are a precious resource, like energy, and we have a moral obligation to ensure they are available for future generations."
Unless "sweeping actions" are taken now, the IDSA warned, the future may look like the pre-antibiotic era: People will die of common infections, and common medical interventions such as surgery, chemotherapy, organ transplantation, and premature-infant care will no longer be possible.
Resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) now kill nearly 100,000 US hospital patients yearly and are increasingly affecting healthy people as well, the IDSA said. Treating resistant infections is costing the healthcare system an estimated $21 billion to $34 billon a year. The group blamed the rising resistance on overuse and improper use of antibiotics, in combination with bacteria's natural ability to evolve.
At the same time, the supply of new antibiotics is drying up. "We're facing a situation where tried and true antibiotics are losing their value at the same time as the pipeline of new drugs to treat these diseases is distressingly devoid of innovative candidate drugs," US Food and Drug Administration (FDA) Commissioner Margaret Hamburg said at the press conference.
The IDSA said only two new antibiotics have been approved since 2008, compared with 16 approved between 1983 and 1987. In 1990, nearly 20 pharmaceutical companies had large, active antibiotic development programs, but that number has dropped to two today, with a few others running limited programs, the group said.
One reason for the drought is that companies are shifting their research to drugs for chronic conditions like diabetes and hypertension, which are easier to get licensed and are more profitable because they are used for years rather days or weeks, the IDSA noted.
FDA as part of problem
But part of the problem, too, is that the FDA has not offered clear guidance about how to design studies for new antibiotics, the IDSA said.
Hamburg acknowledged the regulatory side of the problem. "We need better, more advanced strategies for evaluating the effectiveness of new antimicrobials once they're in development," she said. "This includes new clinical trial designs that are realistic about constraints. . . . We also need to modernize our regulatory pathways so we can expeditiously review new antibiotics, diagnostics, and vaccines as they come before us."
She said FDA scientists have been "working hard to deliver clinical trial recommendations that are scientifically sound, ethical, and feasible." The agency has also been working on guidance for treating various kinds of difficult infections, such as complicated urinary tract and intra-abdominal infections, she added.
Hamburg said the FDA is trying to streamline the antibiotic approval process in two ways: early engagement of the review team with the drug sponsor to identify and address important questions, and seeking to apply the "the best possible science to the review process," which requires a broad partnership with industry, academic, and government scientists.
She added that the FDA needs to "apply cutting-edge science to the regulatory review process," but the tools needed to do that have not been "resourced and attended to in the ways we need if we're really going to deliver on all the promise of science today."
Creating incentives, removing disincentives
First on the list of IDSA recommendations for addressing the resistance problem is "creating incentives (and removing economic and regulatory disincentives) for antibiotic R&D so companies find developing new antibiotics a viable business endeavor."
Another recommendation is to create "an Antimicrobial Innovation and Conservation (AIC) Fee to help pay for drug development and stewardship. The fee would be charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture."
"Antibiotics are a resource that is a shared society benefit. The AIC fee is an equitable way to distribute the costs across society of preserving this resource," said Brad Spellberg, MD, associate professor of medicine at the University of California, Los Angeles, in commenting on the recommendations.
The remaining IDSA recommendations are:
- Recalibrating and better communicating FDA's requirements for new antibiotic approvals
- Funding antibiotic research and development efforts under the Department of Health and Human Services' (HHS) Biomedical Advanced Research and Development Authority (BARDA) and a proposed independent strategic investment firm
- Supporting development of rapid diagnostic tests to identify the causes of infections more quickly
- Designating a leader within HHS to facilitate coordination of federal agencies' efforts to stop antimicrobial resistance
- Promoting the judicious use of available antibiotics in all settings (human and agricultural) through better stewardship programs and infection control practices
- Strengthening public health measures (such as surveillance, data collection, and immunization) and research that leads to new interventions to limit the spread of resistant organisms
- Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be small
The IDSA also praised two pieces of proposed legislation to address antimicrobial resistance, saying they are "good first steps."
At the press conference, Rep. Phil Gingrey, R-Ga., said he plans soon to introduce a bill called the "Generating Antibiotic Incentives Now (GAIN) Act." The bill addresses challenges that companies face with the FDA and is modeled on the Orphan Drug Act of 1983, which created incentives to develop drugs for conditions too rare to attract much investment by the drug industry, he said.
Also getting the IDSA endorsement was the "Strategies to Address Antimicrobial Resistance (STAAR) Act," sponsored by Rep. Jim Matheson, D-Utah. Spellberg said the bill would promote better coordination of federal efforts against drug resistance.
The press conference also included brief comments from Theresa Drew, whose 21-year-old son, Ricky Lannetti, died of a MRSA infection in 2003. Drew recounted how Lannetti, a healthy college football player, fell suddenly ill and was hospitalized a few days later. Despite treatment with five antibiotics, he died 12 hours after being admitted to the hospital, she said.
"It's not good. We need to have something better," she said, referring to antibiotic options.
CDC joins call for action
In other developments, the Centers for Disease Control and Prevention (CDC) today joined in the call for urgent efforts to stop antimicrobial resistance.
"It's not enough to hope that we'll have effective drugs to combat these infections. We must all act now to safeguard this important resource," CDC Director Thomas Frieden, MD, MPH, commented in a press release.
The CDC noted that it recently teamed up with the FDA and the National Institutes of Health to release a draft of "Public Health Action Plan to Combat Antimicrobial Resistance," which lists 11 goals in the areas of surveillance, prevention and control, research, and product development. "The plan is designed to facilitate communication and coordination as well to provide guidance on the most pressing resistance issues and how to address them," the agency said.
Apr 7 IDSA press release
Full text of IDSA's antimicrobial resistance policy recommendations, published in Clinical Infectious Diseases
Apr 7 CDC press release
CDC action plan to combat antimicrobial resistance (32 pages)