By Lauren N Hunt, PharmD, BCPS, Director of Antimicrobial Stewardship for the Western United States at bioMérieux
Interviewing: Peter Beyer, PhD, Senior Advisor for the Antimicrobial Resistance Division at the World Health Organization
Antimicrobial resistance (AMR) has been around for as long as we have had antimicrobials to fight infectious diseases; however, it has been exacerbated in recent years by increased use of antimicrobials and decreased development of new agents. As we navigate COVID-19, the first major global pandemic in more than 100 years, we are again reminded of the power of infectious diseases to disrupt society and our lives.
“Antimicrobial resistance is also a pandemic,” says Dr. Peter Beyer, Senior Advisor for the Antimicrobial Resistance Division at the World Health Organization (WHO). “It is slower and less visible, but it is growing constantly.” Each year, more than 700,000 people die due to resistant infections—a number that could grow to 10 million annually by 2050 if we continue on our current trajectory. Because of the threat that AMR poses to our health, there is a need for global mobilization across all levels—from world leaders and industry, to physicians and scientists, as well as individual patients and their families.
Opportunities and Challenges in Drug Development for Resistant Infections
Antimicrobial availability is a multifactorial problem that includes antibiotic shortages as well as limited new treatments in the development pipeline. Shortages occur for a number of reasons (quality control, manufacturing issues, limited raw materials, natural disasters, etc.) and can contribute to AMR when first line treatment options are not available. In low and middle income countries, access to a wide breadth of antimicrobials is also limited due to costs and governance. As a result, therapy may be less effective and/or more broad than necessary.
The development pipeline challenge is more complex. A major issue Dr. Beyer points out is the current way we buy and pay for reserve antibiotics in particular that does not adequately incentivize drug development. Because antibiotics are generally used in short courses and new, broad-spectrum antibiotics are only used when absolutely needed, the ability for companies to recoup development costs and profit expectations are limited. As a result of these challenges, countries are leveraging legislation to make progress. Globally, the G7 and G20 recognize the need for investment and research and in the US, the DISARM Act and the PASTEUR Act aim to address this problem. Additionally, there has been movement to adjust reimbursement structures in several countries, and there are major investment efforts being made to increase available treatments for a range of infectious diseases.
A recent initiative led by Dr. Beyer helped facilitate the AMR Action Fund, a collaboration between 20 large pharmaceutical companies to invest $1 billion with the goal of bringing two to four new antimicrobials to market over the next decade. The investment comes directly from the pharmaceutical companies and funds phase II and phase III clinical trials for small and medium companies, which are often the most expensive part of development. Dr. Beyer says that this initiative will help buy us time, but that we will still need to make improvements to reimbursement and in other areas to effectively fight AMR.
There are also challenges related to research for new treatments. The number of patients in studies of multi-drug resistant pathogens are often limited and the comparator can vary based on the ‘best available care’. Diagnostics have allowed us to understand more about the organisms than ever before, particularly as it relates to genetic mechanisms of resistance. Newer antimicrobials often target these genes or their precursors; therefore, leveraging diagnostics in the treatment of MDR organisms will be essential moving forward.
Despite the challenges mentioned, companies and scientists have made strides toward new treatments. Experiments with non-traditional antimicrobial treatments, immunomodulators, and new drug combinations have shown promising results, though still have a long road ahead of final approval.
The Role of Diagnostics and Infection Prevention in Curbing Antimicrobial Resistance
“Antimicrobial resistance is so complicated—it’s such a wicked problem,” says Dr. Beyer. Because resistance is constantly evolving, we must take a multi-pronged approach to combat it. Prevention is the best medicine, but we also need to strive for developing new treatments whilst being good stewards of the ones currently in our toolbox.
A key element in antimicrobial preservation and infection prevention/control (IPC) is diagnostic technology. Diagnostics help clinicians identify infections and resistance mechanisms, information they can leverage to prescribe the most appropriate treatment. Dr. Beyer discusses an example where researchers at the Global Antibiotic Development Partnership (GARDP) in collaboration with a small company have pioneered a new drug to treat resistant gonorrhea, an increasingly resistant sexually transmitted infection worldwide. To ensure that the new drug is used appropriately, a diagnostic test will be necessary to determine if a patient is infected with a resistant strain. If a patient does not have a resistant strain, typical first line agents should be used according to the guidelines. The use of diagnostics in combination with clinical decision making and a new antibiotic may help slow the development of resistance against the new drug and preserve its efficacy.
Dr. Beyer also points out that IPC efforts are the cheapest and most efficient measures that can be taken against AMR. While it is possible that the COVID-19 pandemic may help hospitals improve their IPC practices, there are still challenges with implementation and room for innovation. New technologies arriving in the healthcare industry, such as the ability to quickly process large quantities of infection-related data and advances in machine learning, may make infection and resistance surveillance easier for hospitals.
Steps That Everyone Can Take to Combat Antimicrobial Resistance
AMR undermines much of modern health care, which relies on access to effective therapy to prevent and treat infections associated with routine medical procedures. While the focus is largely on governments, industry, scientists, and clinicians, there is plenty that individuals can do to help fight antimicrobial resistance. Besides practicing good hygiene and following your doctor’s instructions when you take antibiotics, you can make choices that support antimicrobial stewardship. This can include voicing support for drug development initiatives and scientific research, supporting adjustments to reimbursement structures, and advocating for more appropriate antimicrobial use in industries like food production. Success and innovation will ultimately come from working together, across industries, professions, and countries.
Opinions expressed in this article are not necessarily those of bioMérieux, Inc.
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