Combating Antimicrobial Resistance A One Health Approach to a Global Threat: Proceedings of a Workshop (2017) / Chapter Skim
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5 Research and Development Actions for Reducing the Need for Antimicrobials
5 Research and Development Actions for Reducing the Need for Antimicrobials
Pages 69-88
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From page 69... ...
Ellen Jo Baron, professor emerita at Stanford University and executive director of medical affairs at Cepheid, described research and development actions in the area of diagnostics. Gregory Daniel, deputy director and clinical professor at the Duke-Margolis Center for Health Policy, explored economic strategies for accelerating research and development for new antimicrobials.
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From page 70... ...
He emphasized the importance of patient-centered messaging about antibiotic-resistant infections: When messaging to the public, he said, CDC emphasizes that "you don't become resistant to antibiotics, but the bacteria in and on your body can." While many more infections are now preventable using existing technologies and better stewardship, he said, discovering how to prevent other types of HAIs and antibiotic-resistant infections will require new approaches and innovation. CDC's Approach to Combating Antibiotic Resistance McDonald provided an overview of CDC's approaches to combating antimicrobial resistance.
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From page 71... ...
He noted that the term antibiotic pressure more aptly refers to pressure on the individual microbiome and collectively on the human population microbiome, the environmental microbiome, and the animal microbiome. CDC's key premise, according to McDonald, is that an intact human microbiome is a primary host defense for preventing antibiotic-resistant outcomes of human health importance.
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From page 72... ...
MI research can be used to tailor antibiotic stewardship to the microbiome of a patient or patient population, said McDonald, as well as to develop better microbiome diagnostics and therapeutics. Therapeutic developments of note, McDonald said, include using fecal microbiota transplantation to reduce resistant bacteria in patients with significantly disrupted microbiomes, such as people with multiple recurrent Clostridium difficile infections and hematopoietic stem cell transplant patients colonized with CRE (Bilinski et al., 2017)
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From page 73... ...
He noted that the concept of using the self-microflora to combat pathogens has existed since 1973, when researchers discovered that feeding adult gut content from a hen to newly hatched chickens inhibits Salmonella colonization (Nurmi and Rantala, 1973)
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From page 74... ...
Understanding the potential effect of an antibiotic alternative requires understanding the animal microbiome, said Johnson. To work toward defining the microbiome, he said, gut samples from thousands of animals have been analyzed.
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From page 75... ...
Other types of vaccines given to humans may also affect antibiotic resistance and/or use, he said, but many lack published data on resistance. Vaccines that warrant further study, according to Klugman, include pneumococcal conjugate vaccine (PCV)
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From page 76... ...
Future viral vaccines, such as one for respiratory syncytial virus, may also affect antibiotic resistance simply because it reduces antibiotic use and therefore the attendant selection of strains in the flora, he suggested.
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From page 77... ...
These pathogens lend themselves to vaccines, which could provide short-term protection for hospitalized patients against nosocomial infection by these pathogens, as well as short-term protection against neonatal sepsis, which is increasingly becoming untreatable, particularly in developing countries, he said. Klugman suggested that alternative approaches to antibiotics such as monoclonal antibodies, which are cells that are derived from a single ancestral cell, can play a major role.
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From page 78... ...
The first are tests for conditions in which immediate patient management decisions will affect both public health and individual patient outcomes, she suggested. For example, a study from France on intrapartum group B strep polymerase chain reaction screening for pregnant women reported that the screening is cost neutral and achieves a 50 percent reduction in the probability of group B strep disease in neonates (El Helali et al., 2012)
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From page 79... ...
The first is any test to rapidly identify patients eligible for clinical trials of new antimicrobial agents at enrollment, such as Ebola tests for Ebola vaccine trials. The second are rapid tests that can definitively rule out bacterial infection at patient presentation, which she predicted would prevent the unnecessary use of antibiotics.
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From page 80... ...
ECONOMIC STRATEGIES FOR ACCELERATING RESEARCH AND DEVELOPMENT FOR NEW ANTIMICROBIALS Very few antibiotic drugs are currently in the pipeline, said Daniel, who cited data from The Pew Charitable Trusts that show that only 41 antibiotics are in some phase of clinical testing (The Pew Charitable Trusts, 2017)
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From page 81... ...
Global efforts and expertise have converged on a fundamental principle of delinking revenues for antibiotics from the volume of use, said Daniel, to ensure return on investment regardless of how often the antibiotic is used. Market entry reward is a pull incentive that is an example of removing the "link" between development costs and revenues by paying for vital antibiotic drugs with public funds, he said.
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From page 82... ...
company either gets a lump sum or gets some yearly payment over 5 or 6 years that, in aggregate, results in a positive net present value, which he estimated at between $1 and $2 billion. Duke-Margolis Approach to Reinvigorating the Antimicrobial Pipeline Daniel explained that the Duke-Margolis Center for Health Policy has analyzed economic pull incentives to outline a path for feasible implementation of economic incentives in the U.S.
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From page 83... ...
Award proposal, which combines market entry reward with a shift to value-based reimbursement for antimicrobials to incentivize innovation. In the proposal, he explained, market entry reward payments phase down over time and continued eligibility for payment requires adherence to a set of conditions: reliable availability of the drug; continued sensitivity of priority organisms; tracking and reporting appropriate prescribing; data collection for post-market studies, if needed; and shifting to alternative payment models that are not volume based.
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From page 84... ...
Top: The distribution of the company's revenue includes a high percentage from the publicly funded market entry reward at the start but decreases subsequently over the 5 years a drug is on the market. Bottom: The cumulative revenue for new antimicrobials would increase with PAVE, but the level of revenue from payers is the same as under the current fee-for-service model.
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From page 85... ...
However, he noted that in the United States today, there is generally much less antibiotic use, fewer antibiotic-resistant strains, and the total number of infections is far below baseline. On the other hand, in the United Kingdom, he reported, the number of nonvaccine strains is expanding rapidly and acquiring resistance, particularly in adults, for reasons that are unclear.
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From page 86... ...
Daniel suggested focusing on the unique economic consequences and post-market issues that drive the use of those products. McDonald wondered whether there is potential for pharmaceutical companies to branch out beyond drug development and adopt an integrated approach to managing the overall health of animals or the health of humans, such as by acquiring diagnostic technology expertise, information technology expertise, and other proprietary knowledge.
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From page 87... ...
Goodman cautioned that if the approval process is too lax, it could affect public health as well as the industry, because it disincentivizes the quality players to make good products. He considers the diagnostic approval process in the United States to be relatively well balanced.
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