Response to the initial alarm bells of the Coronavirus infection, which occurred in Wuhan City, Hubei Province, China in November 2019, was delayed as it was announced to be a type of pneumonia of unknown cause. The WHO warned about traveling to China in January 2020. After much urging, the world was finally properly warned, but the Chinese government did not accurately announce the outbreak situation. Consequently, the delaying of the construction of an epidemic prevention system worldwide has resulted in the direst infection circumstances facing the world today. One year has passed since the WHO named the new coronavirus SARS-CoV-2 infection, COVID-19, and it was declared a pandemic on the 11^th of March 2020, based on the judgment that it corresponds to “an internationally concerned public health emergency”. Suppression of virus transmission by vaccine has finally begun. To date, the pandemic has affected more than 115 million people and killed more than 2.5 million people in 220 countries/regions around the world. There appears to a potential for control in the near future. However, there is a limit to the supply of vaccines and developed countries are competing to obtain the required amount of vaccination necessary for their own citizens. Although the WHO is trying to secure a certain amount for developing countries, it is predicted that a considerable period of time will be required before COVID-19 becomes controllable.

On the other hand, with regard to therapeutic agents for COVID-19, studies began at an early stage. The therapeutic effects of hydroxychloroquine or chloroquine, lopinavir/ritonavir combination, tocilizumab, interferon β1, as well as others, were found to have limited efficacies or no effect. Remdesivir improves recovery time by as much as 30% in critically ill patients, but it is not suitable for mild to moderately ill patients — which comprises the majority of infected individuals. Although the steroid drug dexamethasone is effective in alleviating inflammatory symptoms, its use in mild to moderately ill patients without significant inflammatory symptoms is not recommended. Currently, there are no therapeutic agents available for mildly ill patients who are being treated at home (or in self-isolating accommodations) or for moderately ill hospitalized patients. Nothing is as helpless as a disease without a cure.

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Response to the initial alarm bells of the Coronavirus infection, which occurred in Wuhan City, Hubei Province, China in November 2019, was delayed as it was announced to be a type of pneumonia of unknown cause. The WHO warned about traveling to China in January 2020. After much urging, the world was finally properly warned, but the Chinese government did not accurately announce the outbreak situation. Consequently, the delaying of the construction of an epidemic prevention system worldwide has resulted in the direst infection circumstances facing the world today. One year has passed since the WHO named the new coronavirus SARS-CoV-2 infection, COVID-19, and it was declared a pandemic onthe 11^th of March 2020, based on the judgment that it corresponds to “an internationally concerned public health emergency”. Suppression of virustransmission by vaccine has finally begun. To date, the pandemic has affected more than 115 million people and killed more than 2.5 million people in 220 countries/ regions around the world. There appears to a potential for control in the near future. However, there is a limit to the supply of vaccines and developed countries are competing to obtain the required amount of vaccination necessary for their own citizens. Although the WHO is trying to secure a certain amount for developing countries, it is predicted that a considerable period of time will be required before COVID-19 becomes controllable.

On the other hand, with regard to therapeutic agents for COVID-19, studies began at an early stage. The therapeutic effects of hydroxychloroquine or chloroquine, lopinavir/ritonavir combination, tocilizumab, interferon β1, as well as others, were found to have limited efficacies or no effect. Remdesivir improves recovery time by as much as 30% in critically ill patients, but it is not suitable for mild to moderately ill patients–which comprises the majority of infected individuals. Although thesteroid drug dexamethasone is effective in alleviating inflammatory symptoms, its use in mild to moderately ill patients without significant inflammatory symptoms is not recommended. Currently, there are no therapeutic agents available for mildly ill patients who are being treated at home (or in self-isolating accommodations) or for moderately ill hospitalized patients. Nothing is as helpless as a disease without a cure.

(View PDF for the rest of the abstract.)

The spread of carbapenem-resistant Enterobacterales(CRE) and the high mortality rate of CRE infections are serious problems in the antimicrobial therapy. CRE is a multidrug-resistant that has acquired resistance to various antibacterial, and its resistance genes and antibacterial susceptibility are regional. Antibacterial combination therapy is used to treat CRE infections, but there are concerns about adverse reactions to colistin (CL) and tigecycline (TGC), which are expected to be effective. In recent years, new antibacterial that are effective against CRE have been developed, but it will take some time before they are approved in Japan. For the time being, CRE infections will have to treat by existing antibacterial, and the challenge is how to enhance the ineffective ones to make them effective. Therefore, considering combination therapies that do not use CL and TGC is important for establishing treatment guidelines for future CRE infections.

Assuming that the number of infections caused by AMR will increase in Japan in the future, we calculated the amount of disease loss that could be avoided by using new antimicrobial agents for the treatment of AMR infections. The target diseases were hospitalized pneumonia, hospitalized cystitis, and acute pyelonephritis caused by carbapenem-resistant and multidrug- resistant Enterobacteriaceae and Pseudomonas aeruginosa. We assumed a domestic resistance rate of 10% for all of the above organisms, and a scenario in which 10% of all infections failed primary treatment with conventional antimicrobials, followed by sepsis/bacteremia and death in all cases. The added cost of secondary treatment for sepsis/bacteremia was used as the amount of annual loss due to illness.

As a result, the annual loss due to illness was estimated to be 48.3 billion yen for pneumonia (in-hospital), 1.5 billion yen for cystitis (in-hospital), and 17.5 billion yen for acute pyelonephritis, for a total of 67.2 billion yen per year.

Limitations of this study include:(1) inaccuracy due to the using of predicted number of new cases per year by calculation instead of using the true number of new cases per year,(2) overestimation due to the assumption that the fatality rate of infections caused by AMR was

100%.

The opinions of infectious disease experts are important to confirm whether the resistance rate used in the scenario is appropriate, in addition to the relationship between the infection and the causative organism and detailed information on the causative organism. In the future, it will be necessary to present more accurate amounts by taking this information into account.