Topics “Antimicrobial Resistance (AMR) Seminar” Held History and Current Status of Infectious Disease Control: Lessons from Semmelweis
The “Antimicrobial Resistance (AMR) Seminar: Lessons from Semmelweis” was held on November 22, 2019, at the Japan Medical Association Hall (Bunkyo Ward, Tokyo) as a joint event organized by the Japan Medical Association (a public interest incorporated association) and the JPMA, in conjunction with Antimicrobial Resistance (AMR)AMR) Awareness Month, was held on November 22, 2019, at the Japan Medical Association Hall (Bunkyo Ward, Tokyo).At this seminar, leading experts from industry, academia, and government delivered presentations on the history of infectious disease control, the current status of AMR countermeasures in Japan, and the current state of new antimicrobial drug development. Furthermore, a panel discussion conveyed a message aimed at deepening the understanding among the general public, healthcare professionals, and government officials that the AMR issue is an urgent social problem.
Scenes from the Venue
Opening Remarks
In his opening remarks, Dr. Yoshitake Yokokura, President of the Japan Medical Association, noted that Semmelweis, born in Hungary in 1818, is credited with advocating for prevention through rigorous handwashing as a measure against puerperal fever—a major threat in the mid-19th century—and that a bust of him was installed at the headquarters of the Japanese Red Cross Society in 2018 to commemorate the 200th anniversary of his birth.Regarding efforts to combat antimicrobial resistance (AMR), he noted that since Japan’s first “Action Plan for Antimicrobial Resistance (AMR) Countermeasures” was formulated in 2016, efforts have been made to raise awareness of the importance of the appropriate use of antimicrobial agents, and that the Japan Medical Association has been actively involved in these efforts.
, Japan Medical Association
Chairman: Mr. Yoshitake Yokokura
Presentation 1 The History of Infectious Diseases and Current Challenges: Learning from Semmelweis’s Teachings
, Representative Director, Japan Health Policy Institute (NPO); Professor Emeritus, National Graduate Institute for Policy Studies
Mr. Kiyoshi Kurokawa
In his lecture, Kiyoshi Kurokawa, Representative Director of the Japan Health Policy Institute and Professor Emeritus at the National Graduate Institute for Policy Studies, noted that in the era before the development of bacteriology by Pasteur and others, Semmelweis had focused on the differences in puerperal fever incidence rates between obstetric facilities,and noted the similarities in autopsy findings between patients who died from puerperal fever and those who died from other diseases, leading him to strictly enforce hand washing with disinfectant after every delivery.He also pointed out that in today’s globalized world, when infectious diseases caused by drug-resistant bacteria and viruses—spread across regions and nations—suddenly become a major issue, there is great value in learning from Semmelweis’s foresight in implementing countermeasures based on hypotheses derived from his observations.
Presentation 2 Issues Surrounding AMR (Antimicrobial Resistance) ~
, Director, International Center for Infectious Diseases, National Center for Global Health and Medicine Hospital, National Research and Development Agency
Mr. Takao Omagari
Mr. Takao Omagari, Director of the Center for International Infectious Diseases at the National Center for Global Health and Medicine Hospital, presented on the various measures implemented in Japan to date in accordance with the Action Plan for AMR, as well as their outcomes and challenges.
Regarding challenges, it was noted that, compared to European countries, the rate of accurate knowledge regarding antimicrobial resistance and antimicrobial agents among the Japanese public is low, and that it is necessary to further increase opportunities for people to access correct information.Furthermore, regarding community-based AMR countermeasures, he stated that support is needed for infection control and medical care at small and medium-sized hospitals and elderly care facilities; it is necessary to develop guidance and further expand the network of medical institutions eligible for infection prevention incentives to broaden support.Regarding the appropriate use of antimicrobials, he noted that while the management of the common cold has improved year by year—with the antimicrobial prescription rate falling from 60% in 2015 to 30% in 2017—this progress remains insufficient.He also noted that while the overall volume of antimicrobial use decreased by 10.6% in 2018 compared to 2013—thanks to initiatives such as the “Guidelines for the Appropriate Use of Antimicrobials”—the use of injectable antibiotics increased by 10.0%, primarily due to their use in patients aged 65 and older.He also pointed out various other challenges, including the introduction of drug-resistant bacteria from overseas, One Health initiatives, shortages in the supply of antibiotics, and a stagnation in the development of new antibiotics.
Meanwhile, as an achievement, he introduced the establishment of the Joint Platform for Infection Control Collaboration (J-SIPHE). He explained that by visualizing the microbial detection status and actual antimicrobial usage at each medical institution—and enabling comparisons with other facilities and national data—the platform has become a useful tool in combating drug-resistant bacteria.
Finally, he outlined his vision: while the past 15 years have been dedicated to raising awareness of the concept of appropriate antimicrobial use, modifying dosages and administration methods, and meeting unmet medical needs through expanded indications, it is crucial that over the next 10 years, Japan work with various societal stakeholders to advance AMR countermeasures and emerge as a global leader, thereby contributing to the development of healthcare and society.
Lecture 3 The Japan Pharmaceutical Manufacturers Association’s Initiatives in Infectious Disease Control
Akira Kawahara, Executive Director, JPMA
Akira Kawahara, Executive Director of the JPMA, first provided an overview of the JPMA and the current state of the pharmaceutical industry, followed by an explanation of the JPMA’s initiatives regarding infectious disease control, particularly its efforts to combat antimicrobial resistance (AMR).
He noted that within the AMR Action Plan, the pharmaceutical industry is expected to play a particularly significant role in “the appropriate use of antimicrobials” and “research, development, and drug discovery.” While the industry supplies healthcare settings with treatments for various pathogens such as bacteria and viruses, he stated that, depending on the type of pathogen, preventive and therapeutic measures are still insufficient.
Furthermore, the JPMA highlighted its various outreach and awareness-raising activities regarding AMR countermeasures, carried out in collaboration with domestic infectious disease-related academic societies, medical associations, and other relevant organizations, as well as through partnerships with the Asia Pharmaceutical Association Council (APAC) and the Nikkei Asia-Africa Infectious Diseases Conference.Furthermore, regarding the health agenda for the 2019 G20 Osaka Summit, the association proposed the need to create an environment that ensures the sustainability of research and development and drug discovery—specifically, pull-type incentives(1) Market Entry Reward, (2) Transferable Exclusivity Extension, (3) Purchase Guarantees, and (4) a system for pre-approval review of drug prices based on drug profiles—to ensure the sustainability of research and development and drug discovery—and noted that a commitment to consider these measures was included in the Leaders’ Declaration.
Finally, Executive Director Kawahara pointed out that there is no single “trump card” in the fight against AMR and that steady, persistent efforts are required. In particular, as a research-and-development-oriented pharmaceutical industry, he believes it is of utmost importance to introduce “pull-type” incentives that lead to sustained research and development of antimicrobial agents at an early stage, and to foster collaboration among industry, academia, and government to bring these incentives to fruition.However, he acknowledged that the hurdles—in terms of research costs, funding for incentives, and securing public consensus for the system’s implementation—are significant, and expressed his determination to move forward while gaining public understanding.
Lecture 4 Issues Related to Infectious Diseases from a Government Perspective and International Cooperation
Mr. Satoshi Shimada, Specialist, Tuberculosis and Infectious Diseases Division, Health Bureau, Ministry of Health, Labor and Welfare
Satoshi Shimada, Specialist Officer at the Tuberculosis and Infectious Diseases Division, Health Bureau, Ministry of Health, Labor and Welfare, began by pointing out that, due to the issue of tuberculosis in Japan and the increase in the movement of people accompanying globalization, infectious diseases are no longer solely a domestic problem; he also spoke about the need to ensure that antimicrobial agents remain valuable resources for the future.
During his presentation, Mr. Shimada noted that Japan is currently implementing an AMR Action Plan that incorporates international cooperation in addition to the five major pillars of the World Health Organization’s (WHO) Global Action Plan on AMR (awareness-raising, surveillance,infection prevention and control, appropriate use of antimicrobials, and promotion of research and development), and is taking action based on an AMR Action Plan that includes international cooperation. He also discussed the results of implementing this plan, citing several examples.For example, regarding public awareness, he reported on activities to raise public awareness by effectively utilizing collaborations with celebrities and animated content. Regarding surveillance activities, he noted that trend survey reports summarizing antimicrobial usage and the prevalence of resistant bacteria are released to the National Public Awareness Conference.Furthermore, regarding infection prevention and control, he mentioned the introduction of a new incentive payment for hospitals that have established Antimicrobial Stewardship Teams (ASTs).He also noted that, as part of efforts to promote appropriate use, the “Guidelines for the Appropriate Use of Antimicrobials, First Edition” was published in 2017, and that a second edition—which includes additional guidance for toddlers and infants—is currently being prepared.
As part of efforts to promote research and development, he reported that support for drug discovery and development targeting drug-resistant bacteria—which the WHO considers a priority—is being provided through the Ministry of Health, Labor and Welfare’s Scientific Research Grants, the Japan Agency for Medical Research and Development (AMED), the Global Health Technology Promotion Fund (GHIT Fund), and other organizations.Furthermore, in addition to such “push-type” support, he emphasized the need for “pull-type” incentives to support new drugs after they are launched. He noted that, in order to realize these incentives, the necessity of new antimicrobial agents and their development must be widely publicized and understood by the general public.
Panel Discussion
Moderator
- Mr. Ryoji Noritake, Director and CEO, Japan Health Policy Institute (NPO)
- Ms. Kaori Matsuzawa, Adjunct Fellow and Attorney at Law, Japan Health Policy Institute (NPO)
Panelists
- Dr. Takao Omagari, Director, International Center for Infectious Diseases, National Center for Global Health and Medicine Hospital, National Research and Development Agency
- Akira Kawahara, Executive Director, JPMA
- Mr. Satoshi Shimada, Specialist, Tuberculosis and Infectious Diseases Division, Health Bureau, Ministry of Health, Labor and Welfare
- Mr. Satoshi Kamayachi, Standing Director, Japan Medical Association (Public Interest Incorporated Association)
- Ms. Satoka Suzuki, Director, Center for Antimicrobial Resistance Research, National Institute of Infectious Diseases
Building on the previous presentations, Mr. Satoshi Kamayatsu, Standing Director of the Japan Medical Association, and Ms. Satoka Suzuki, Director of the Center for Antimicrobial Resistance Research at the National Institute of Infectious Diseases, joined the discussion. They addressed the current status and challenges of domestic efforts to combat AMR, as well as Japan’s role in the international community and future prospects.
Dr. Kamayachi explained that the “Guidelines for the Appropriate Use of Antimicrobials” are highly regarded in daily clinical practice as a catalyst for raising awareness of AMR, and that further public awareness campaigns are needed.He also reported that ensuring patients take prescribed medications as directed is the most critical task for primary care physicians, and that initiatives are underway through the Japan Medical Association’s Continuing Medical Education System and the Primary Care Physician Skills Training Program. Furthermore, looking ahead, he highlighted the issue of ensuring a stable supply of antimicrobial drugs—a challenge in clinical settings—and advocated for a system that secures not only active pharmaceutical ingredients but also the antimicrobial drugs that are truly necessary.
Permanent Director, Japan Medical Association Mr. Satoshi Kamayachi
Mr. Suzuki reviewed the trends in surveillance data on drug-resistant bacteria and their relationship to initiatives in domestic healthcare settings. Looking specifically at methicillin-resistant Staphylococcus aureus (MRSA), a representative drug-resistant bacterium,he noted that while the resistance rate—which stood at around 70% in the early 2000s—has now dropped significantly to 47%, though it has not yet reached the action plan’s target of 20%. He explained that the “Infectious Disease Control Surcharge,” a measure within the medical fee schedule, contributed to this decline.Additionally, examples were cited of multidrug-resistant Pseudomonas aeruginosa (MDRP), which has shown a marked decline in recent years; vancomycin-resistant enterococci (VRE), whose resistance rate is significantly lower and better controlled in Japan compared to other countries;multidrug-resistant Acinetobacter (MDRA). The presentation outlined how MDRP was successfully reduced through improved handling procedures for urine and other specimens from hospitalized patients, while outbreaks of MDRA and VRE were suppressed through thorough monitoring of the current situation—driven by mandatory reporting of all cases—and rigorous hospital infection control measures.Regarding MDRA, it was emphasized that outbreaks often originate from infection cases in individuals with a history of overseas travel, highlighting the importance of controlling drug-resistant bacteria not only in Japan but also internationally. It was pointed out that, in light of the expected increase in international travelers, even greater attention must be paid to hospital infection control measures than ever before.Furthermore, from the perspective of international contribution, he noted that in developing countries with high numbers of patients with drug-resistant infections, the inappropriate use of new drugs can quickly lead to the emergence of drug-resistant bacteria. To address this challenge, he stressed the importance of capacity building for microbiology laboratories in these countries.
National Institute of Infectious Diseases Director, Center for Antimicrobial Resistance Research
Ms. Satoka Suzuki
Dr. Omagari acknowledged that while there have been some achievements in the appropriate use of antimicrobials and infection prevention measures, efforts to raise public awareness—despite ongoing efforts—have yielded less visible results, and he emphasized the need to continue these efforts.He also emphasized the need to view infection control from a broader perspective—including outpatient settings and facilities for the elderly—and, as part of the outlook for future action plans, called for more in-depth international efforts, such as visualizing the actual state of infectious diseases in local communities and implementing measures against drug-resistant bacteria from overseas.He expressed the view that the context specific to Asia and Japan differs from the lists of causative bacteria and various guidelines created by the WHO, and emphasized the need to communicate perspectives tailored to each environment within the international community.
Mr. Shimada acknowledged that certain progress had been made in terms of public awareness campaigns and reducing antimicrobial usage, and expressed his intention to build regional networks for AMR countermeasures moving forward. He also mentioned both “push” and “pull” incentives as part of measures to promote new drug development, and this perspective was shared by the audience.
Executive Director Kawahara, speaking from the perspective of pharmaceutical companies, emphasized the importance of continuing to steadily provide information on appropriate use. He also noted that, in clinical settings—where appropriate use is a prerequisite—an incentive system that maintains an environment where new drugs can be continuously launched as a business, and, as a prerequisite for this, expressed his hope that public awareness of the benefits of new drugs to society will grow widely among the general public.
Finally, Mr. Omagari concluded the panel discussion by noting that while efforts have been made to educate the general public on what drug resistance and appropriate use entail, it is essential for us to recognize—and for the public to understand—that reducing drug-resistant bacteria and developing new drugs come with significant costs.
Japan Health Policy Institute, Director/CEO Mr. Ryoji Noritake
, Adjunct Fellow at the same institution
Ms. Kaori Matsuzawa, Attorney at Law
Scene from the Panel Discussion
Key Takeaways and Closing Remarks
In his closing remarks, Joji Nakayama, Chairman of the JPMA, emphasized the importance of continuing to promote partnerships among industry, academia, government, and the private sector to address the issue of AMR. He noted that this requires a division of roles focused on promoting the appropriate use of antimicrobials in clinical settings, conducting public awareness campaigns for patients, and developing new drugs as needed.Chairman Nakayama also touched on the current status of AMR initiatives, noting the need for regular information sharing through opportunities such as this seminar, which brings together stakeholders from industry, academia, government, and civil society, and summarized the outcomes of the seminar.
Mr. Joji Nakayama, Chairman, JPMA
Summary
Under the Action Plan to Combat AMR, which was announced in 2016, ongoing efforts are being made to address AMR through various measures.Furthermore, the Leaders’ Declaration from the G20 Osaka Summit held in June 2019 included a statement calling for an analysis of push- and pull-type incentive mechanisms to identify the best models for the research and development of new treatments for AMR, and for a report on this to be submitted to the relevant G20 ministers.Momentum to strengthen these efforts is growing, and the role played by research-based pharmaceutical companies—such as further promoting appropriate use and developing new treatments for AMR—is expected to become increasingly significant.
(International Affairs Committee, Global Health Subcommittee, Infectious Diseases Group: Yusuke Ariyoshi, Masashi Kawata, Takafumi Kuroda, Tomoko Tatenbayashi, Hiroyuki Yoshida )