'A silent pandemic': How Japan is curbing antibiotic resistance, $5 at at timeAntimicrobial resistance is a "silent pandemic," posing huge threats to public health while raising little attention. To curb resistance, doctors must use antibiotics sparingly and responsibly. This report is the first in a series comparing antibiotic use in Japan and the United States, with a focus on outpatient pediatrics. It was supported by a reporting fellowship from the Association of Health Care Journalists and The Commonwealth Fund.About a decade ago, the Japanese government spotted a worrying pattern: Pediatricians were doling out a ton of antibiotics, well beyond what should be needed to treat the bacterial infections coming through their doors. Antibiotics treat bacterial infections, not those caused by viruses, fungi or parasites. Yet doctors were often sending young patients home with antibiotics for illnesses unlikely to be bacterial. Treating nonbacterial infections with antibiotics can fuel antimicrobial resistance (AMR) and the rise of superbugs by unnecessarily exposing bacteria to the drugs, pressuring those bacteria to evolve strategies to survive. Resistant bacteria can then spread their adaptations to others, thereby compounding the problem.In the long run, resistance could make common infections impossible to treat with existing drugs, raising the risk of serious illness and death across the population.When pediatricians in Japan did treat bacterial infections, they were overusing the antibiotics that are likely to fuel resistance "broad-spectrum" drugs that target many bacteria at once. When compared against 35 other high-income countries in 2015, Japan ranked dead last in the appropriateness of antibiotic choices for kids under 5.One way to slow the development of AMR is to get antibiotic prescriptions under control. So Japan focused on one of its biggest sources of problematic antibiotic use: pediatric outpatient clinics."The clinics are a particular problem," said Dr. Yusuke Okubo, chief of clinical epidemiology and health services research at the National Center for Child Health and Development, a research center and hospital in Tokyo. Looking at Japan's overall antibiotic use, "90% of prescriptions are [from] outpatient clinics, not hospitals," Okubo told me. (Outpatient practices account for a similar proportion of antibiotic prescriptions in the U.S.)A large proportion of problematic prescriptions were being written for children under 3 years old, especially those with upper respiratory tract infections, which nine times out of 10 are caused by viruses, Okubo said. The stomach bug gastroenteritis was another biggie for overprescription, despite most often being caused by a virus.Government officials hatched an idea: What if each time a pediatrician chose not to prescribe an antibiotic in these cases, they earned a small financial reward a tip for making a better choice? Each tip would be small, amounting to about $5 per claim at today's exchange rate, but could translate to thousands of extra dollars of annual income for individual clinics. That's no small matter for Japanese pediatricians, who Okubo estimates earn roughly $90,000 to $100,000 a year.This incentive program, rolled out in 2018, has proved a success, so much so that it's since been expanded to cover more patients, more clinics and a wider variety of diseases. But what made the program work? I went to Japan to find out what systemic and cultural factors contributed to the program's success. Ultimately, I wanted to see whether other countries, like the U.S., could learn from this nationwide experiment.Japanese pediatricians historically overused antibiotics, but an insurance policy is helping to change that. (Image credit: Susumu Yoshioka via Getty Images)The quietly rising threat of resistanceWith bacteria, as with animals, it's survival of the fittest. When exposed to antibiotics, a percentage of bacteria die, while others survive. That surviving population has traits that help them withstand the drug's effects, which are encoded in "resistance genes." Bacteria can transfer those genes to the next generation by multiplying, as well as physically pass those genes to nearby bacteria. Plus, they can pick up new resistance genes through random DNA mutations.All antibiotics come with the risk of pressuring bacteria to evolve resistance it's an inherent feature of the drugs. However, broad-spectrum drugs carry the greatest risk, because they place pressure on a wider variety of bacteria than narrow-spectrum drugs do. The 2015 cross-country comparison found that Japanese doctors prescribed antibiotics with the lowest risk of resistance only 35% of the time, meaning most antibiotic prescriptions were for broader-spectrum drugs.It's sometimes necessary to use broad-spectrum drugs such as when an infection is resistant to narrow-spectrum options but using broad-spectrum antibiotics when they're not needed hastens the development of AMR. So does using antibiotics for nonbacterial infections. In both scenarios, you're introducing evolutionary pressure that could have otherwise been avoided.Data showed that pediatricians in Japan often prescribed antibiotics for common childhood infections that were likely viral. Overprescription was a particularly big problem for children under 3. (Image credit: recep-bg via Getty Images)Globally, resistance is rising among common disease-causing bacteria; it's far outpacing the development of alternatives to antibiotics. In 2021, resistant bacterial infections directly caused 1.14 million deaths worldwide and contributed to another 3.57 million deaths. Those numbers could climb dramatically by 2050 if swift action isn't taken now.Common pathogens already show high rates of resistance in Japan, and resistant germs contribute to thousands of deaths each year, with most occurring among older adults. People over 65 make up about 30% of Japan's population. As that percentage grows in the coming years, AMR-related illness may also increase, health officials worry. Japan's youngest residents are also at risk, though, as resistant bacteria can sometimes pass from mothers to newborns at birth and can cause serious complications, like sepsis. Resistance has also been detected among respiratory bugs that frequently infect kids, such as Mycoplasma pneumoniae, said Dr. Takemi Murai, deputy head of the Infectious Diseases Division at Nagano Children's Hospital in Azumino. "There have been outbreaks of Mycoplasma that are resistant to antibiotics," he said.Yet not long ago, the unrestrained use of antibiotics was a mainstay of Japanese medicine. (I'll dig into the myriad reasons why in later installments of this series.)National insurance data sampled from 2005 showed that 60% of patients in Japan with nonbacterial upper respiratory tract infections were prescribed antibiotics, mostly broad-spectrum ones like third-generation cephalosporins, macrolides and quinolones. Most of those prescriptions came from clinics.Something had to shift.Tips for appropriate treatmentIn 2016, Japan got serious about reducing its antibiotic misuse, releasing its first National Action Plan on Antimicrobial Resistance. It aligned with a global plan from the World Health Organization, which aimed to raise awareness of AMR and optimize the use of antimicrobials, including antibiotics, among its member states. Two of Japan's big goals were to slash overall antibiotic use by 33% and broad-spectrum antibiotic use by 50% by 2020. The country came very close to hitting those ambitious targets by the deadline, and doing so was no small feat. The tipping program was just one of a slew of initiatives introduced to improve AMR awareness and antibiotic use.The Japanese government created posters to raise awareness of AMR. This example features the popular anime character Amuro Ray, whose first name is similar to "AMR," so his inclusion in the campaign plays off of a pun. (Image credit: Courtesy of Dr. Yusuke Okubo)Prior to the incentive's introduction, Japan's Ministry of Health, Labour and Welfare (MHLW) whose role is somewhat analogous to the U.S. Department of Health and Human Services rolled out educational campaigns for doctors and patients and wrote a manual for antibiotic use, with the first edition directed primarily at outpatient doctors. It emphasized that most acute respiratory tract infections and acute diarrheal diseases don't require antibiotics. Among kids, children under 5 saw the highest antibiotic prescription rates, often receiving the drugs for respiratory infections. Data showed this overprescription problem was the worst in children under 3 being assessed for upper respiratory infections or acute gastroenteritis. The government's solution? Pay doctors extra to withhold antibiotics when faced with cases that don't warrant them."If the clinicians provide more appropriate medical services, we add additional payment," said Dr. Takuma Kato, a counselor at the Permanent Mission of Japan to the United Nations who previously worked on the incentive program for MHLW. In this case, they pay "a little bit more" when doctors don't give patients antibiotics for illnesses that are likely viral, he said.A "little bit more" is accurate. Each tip is 800 yen, equivalent to about $7.20 when the program launched in April 2018 and about $5 at today's exchange rate.Here's how it works: A caregiver brings in their sick infant or toddler for an initial visit, and the pediatrician determines the child likely has an acute upper respiratory tract infection or gastroenteritis. These illnesses are typically caused by viruses, so the doctor decides not to provide an antibiotic. The doctor explains this rationale to the caregiver and provides guidance for home care. If the appointment checks those boxes, the clinic can claim an extra 800 yen when they seek reimbursement.Because mild viral infections typically resolve on their own in a few days, a strategy called "watchful waiting" can help clarify if a bacterium is actually at fault. So if a doctor does prescribe an antibiotic at the first visit, they'll often encourage the caregiver to bring the child back if their condition remains the same or worsens within a few days. The incentive and this "waiting" strategy go hand in hand.There are a few technicalities. For example, the children being assessed must have no underlying conditions that might complicate their case, such as a weakened immune system. If children test positive on a formal diagnostic test for influenza or COVID-19, the incentive cannot be claimed. To qualify for the incentive, clinics must specialize in pediatrics and use a "comprehensive" payment system, meaning patients pay a standardized amount for the whole appointment rather than the itemized "fee for service" that is ubiquitous in the U.S.Despite this fine print, the perk is pretty appealing for the clinics that claim it. "I think pediatric doctor associations are really happy," Okubo said.Doctors say "small incentives add up"The Japanese government generally incentivizes doctors to adjust their behaviors, rather than penalizing them for poor practices, Okubo said."It's a constructive message from the government: 'You changed your behavior, so we'll pay something,'" Okubo said. "This constructive approach motivates physicians, especially pediatricians, to apply their common sense to their actual practice."This system is readily accepted by Japanese doctors, who have historically held a lot of political power, Kato noted. Just like in the U.S., their professional groups, such as the Japan Medical Association, lobby the government and typically push against policy proposals that they view as potential threats to their bottom line.By contrast, an incentivizing approach is "very, very welcome, especially by the doctors' associations," said Dr. Norio Ohmagari, director of disease control and prevention at the National Center for Global Health and Medicine, part of the Japan Institute for Health Security (JIHS) in Tokyo. Ohmagari also leads the AMR Clinical Reference Center, which collaborates with the WHO on AMR countermeasures.Dr. Yusuke Shibata has been treating patients at the Shibata Pediatric Clinic in Tokyo since the 1990s. He appreciates the incentive in that it both boosts his profits and aligns with his stance that the careless use of antibiotics should be avoided. (Image credit: Nicoletta Lanese)Doctors I asked confirmed that they like the incentive, namely because it boosts their profits."I apply for the pediatric antibiotic appropriate use support premium each time" it's applicable, said Dr. Yusuke Shibata, who runs the Shibata Pediatric Clinic in Asakusa, a historic district in Tokyo's Taito ward. "I appreciate the premium, as pediatric clinics already have low profits" compared with clinics that care for adults, Shibata told me in an email after I visited his clinic.For first visits with kids under 6, clinics are paid a base rate of 6,040 to 7,210 yen, or about $38 to $45 at current exchange rates. An extra 800 yen (about $5) increases that fee by more than 10% "a huge amount," Okubo emphasized.Shibata estimates that his clinic sees about 30 to 40 patients with an acute respiratory infection or diarrhea each week, depending on the season. He can potentially claim the incentive for the first visit with each of these patients, assuming they don't have any conditions that would disqualify the claim. On the high end, Shibata estimates that he might claim the incentive 180 times in a single busy month, which would total 144,000 yen, or about $900.Dr. Atsushi Miyahara of the Karugamo Clinic in Tokyo frequently claims the antibiotic incentive. He's long been careful about antibiotic use, and the incentive rewards him for those efforts. (Image credit: Nicoletta Lanese)Dr. Atsushi Miyahara, who runs the Karugamo Clinic in the Setagaya-ku ward in Tokyo, said he was already conservative about using antibiotics so the incentive rewards him for sticking with his status quo.Fifteen years ago, when Miyahara opened his clinic, he noticed that other physicians prescribed a lot of antibiotics, and he questioned the practice due to the potential to fuel resistance. He provides his patients with informational flyers that explain the risks of resistance and how avoiding unnecessary prescriptions can reduce that risk. When antibiotics are needed, he predominantly uses narrow-spectrum drugs that pose a relatively low risk of resistance. Miyahara said the local government and medical associations announced the antibiotic incentive when it was launched, and he felt its introduction has been very positive. It's increased his revenue and encouraged him to continue his stewardship practices. He estimates that for every 50 of his first visits with patients, he claims the incentive 10 to 15 times, so it applies to at least 20% of those visits.An informational flyerDr. Atsushi Miyahara provides to his clients. It states that the clinic takes measures against AMR, explaining that antibiotics are not used for viral illnesses, and for bacterial infections, the narrowest-spectrum options are prioritized. (Image credit: Nicoletta Lanese)The incentive's impactBecause some pediatric clinics qualified and others didn't due to fee-for-service clinics being excluded Okubo and his colleagues could directly measure whether the policy worked. To assess the incentive's effects in its first year, the researchers looked at insurance claims from over 10,000 medical facilities from just before and after the policy's introduction. About 3,000 of the facilities qualified and claimed the incentive 316,770 times, totaling 253 million yen ($2.29 million at the time). These eligible clinics saw a 17.8% reduction in their total antibiotic use over a year without any negative effects for patients, such as higher hospitalization rates.Science Spotlight(Image credit: Marilyn Perkins / Future)Science Spotlight takes a deeper look at emerging science and gives you, our readers, the perspective you need on these advances. Our stories highlight trends in different fields, how new research is changing old ideas, and how the picture of the world we live in is being transformed thanks to scienceTo see if those effects lasted, the team drew years of data from over 165,000 young children who went to either eligible or ineligible clinics. Within the first month of the policy's implementation, the former group of children saw a nearly 45% reduction in total antibiotic prescriptions, compared with the other kids. Cumulatively over the next four years, their overall antibiotic use and broad-spectrum-antibiotic use was 20% and 24% lower, respectively.The decrease in antibiotic prescriptions did not come with an uptick in hospitalizations or healthcare costs, although there was a slight increase in the total number of doctor's visits. But that's what you'd expect as doctors track an infection over time, Okubo explained, meaning they likely employed the watchful-waiting strategy and had parents bring their kids back in if they didn't improve quickly.Okubo's team has continued to track pediatricians' antibiotic use, and he noted that they're seeing "spillover effects" among age groups not covered by the incentive. In the under-20 age group, outpatient antibiotic prescriptions fell by 50% between 2011 and 2022. He thinks the incentive is a key driver of this trend, directly reducing prescriptions for the youngest kids while also triggering ripple effects in older groups. (This research will soon be published in a peer-reviewed journal.)That said, there's room to improve doctors' selection of antibiotics when they are used, as the ratio of broad- to narrow-spectrum drugs is still too high. "Total antibiotic use was reduced, but its quality should be improved further," Okubo said.Okubo conducts research at the National Center for Child Health and Development in Tokyo. As a research center and Japan's largest children's hospital, it aims to deepen the understanding of children's health and development while providing advanced medical care. (Image credit: Nicoletta Lanese)The incentive's evolutionWhile the 800-yen tip has proved significant to clinicians, the incentive represents a very small slice of overall government healthcare spending, which totaled 468 billion yen ($3.1 billion) in 2022."This program is not large compared to the whole budget," Dr. Kosuke Sasaki, who works in the MHLW's health insurance bureau, told me. The program's budget has no upper limit, so if the number of claims from clinics increased, there isn't a cap on how many could be paid out. "The number of doctors using this program has increased while the number of antibiotic prescriptions has decreased since the start," Sasaki's colleague Dr. Tomonori Aoki added, noting that the government isn't concerned about how to pay that rising bill. The program's measurable impact and low price tag may explain its growth over the years. Every two years, Japan's Ministry of Finance hands the MHLW its slice of the government budget, and MHLW then revises the pricing for drugs, medical devices and healthcare services. The antibiotic incentive falls under this revision process and has been expanded several times.The Ministry of Health, Labour and Welfare is housed in an unremarkable building in Central Tokyo. It sets the prices for pharmaceuticals, medical devices and healthcare services nationwide. (Image credit: Nicoletta Lanese)During its first revision in 2020, the incentive was extended to children under 6. In 2022, ear, nose and throat specialists (ENTs) newly qualified for the incentive; like pediatricians, they treat many acute infections in kids and tend to overuse antibiotics, insurance data suggested. That same year, doctors could start claiming the fee for ear infections and sinus infections."I see a tendency for pediatric clinics to avoid prescribing antibiotics, but I do see some ENT clinics prescribing antibiotics carelessly," Shibata, the clinic owner in Asakusa, Tokyo, told me. So ENTs seem to be a logical next target. In 2024, a separate, facility-level incentive was introduced as a complement to the 800-yen incentive. It encourages clinics to submit data to a government database that tracks antibiotic use. If first-line, narrow-spectrum antibiotics make up a certain percentage of the clinic's overall prescriptions, that clinic earns extra money, Okubo explained. Related storiesDangerous 'superbugs' are a growing threat, and antibiotics can't stop their rise. What can?Antibiotic found hiding in plain sight could treat dangerous infections, early study findsMetal compounds identified as potential new antibiotics, thanks to robots doing 'click chemistry'Ultimately, the 800-yen incentive helped put AMR on the radar of doctors who didn't take it as seriously as experts like Kato, who told me "AMR is kind of my life's work." Kato and researchers like Okubo see the program as a success, although they pointed to room for improvement in antibiotic selection. Ministry officials like Sasaki and Aoki said the program is easy to implement and makes a difference. Clinic doctors like Shibata and Miyahara appreciate the incentive and use it consistently. All in all, at just $5 a claim, the incentive has been remarkably effective.In speaking with experts in Japan and the U.S., I've learned that U.S. doctors have historically faced the same pressures and showed similar lapses in antibiotic use that Japanese doctors have. However, the U.S. does not have an incentive program like Japan's. Should it launch one? In the next installment of this series, I'll explore a central feature of this problem: the motivations behind pediatricians' antibiotic misuse. What are they, and do those motivations differ between doctors in the U.S. and Japan? Answers to those questions will help determine whether a similar incentive might have the same impact in both places.