Antimicrobial resistance (AMR) has reached a critical situation globally, prompting urgent national responses to this escalating crisis, including the prioritization of novel antibiotic research. In 2016, Japan initiated a national AMR action plan that promoted appropriate antibiotic use in the country and encouraged a national environment conducive to mitigation measures. However, tackling AMR remains difficult. From an epidemiological perspective, this challenge now extends beyond severe infections, impacting common community-acquired infections, including uncomplicated urinary tract infections (uUTls) and gonorrhea. In uUTIs, the rising prevalence of extended-spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli diminishes the effectiveness of current, routinely used oral antibiotics, necessitating an exploration into innovative solutions. Similarly, the growing resistance of Neisseria gonorrhoeae to antibiotics such as azithromycin raises concerns about the efficacy of current therapeutic options for gonorrhea, which is a highly prevalent sexually transmitted infection. In Japan, since the removal of azithromycin as the recommended first-line treatment, there are no oral first-line antibiotics available to treat gonorrhea. Therefore, novel oral antibiotics are urgently needed for both serious and commonly occurring community-acquired infections. This narrative review discusses the limited availability of novel antibiotics in Japan, the distinctive features of the Japanese antibiotic repertoire and AMR epidemiology, and potential alternative oral treatments for community-acquired infections, including uUTIs and gonorrhea. Japan has been making significant advances toward tackling the AMR crisis through an updated national action plan, AMR policy changes, and innovative approaches to developing novel antibiotics. Substantial international cooperation and the engagement of diverse industry sectors are essential to address the pressing issue of AMR.

Background: In Western studies, lung microbiome changes are reported in patients with chronic obstructive pulmonary disease (COPD) and are associated with poorer outcomes, but similar studies in Asian patients or those with less severe COPD are limited. Methods: The Acute Exacerbation and Respiratory InfectionS in COPD Japan (AERIS-J; jRCT1080224632/NCT03957577) was a prospective, non-interventional study to evaluate sputum microbiome diversity at baseline and after 12 months (V2; exploratory analysis), in patients aged 40– 80 years with stable COPD (June 2019–June 2022). Baseline sputum potentially pathogenic organisms (PPOs) were identified. Blood cell counts and COPD Assessment Test (CAT) scores were collected at baseline and COPD symptoms measured over 12 months using the Evaluating Respiratory Symptoms in COPD and EXAcerbations of Chronic pulmonary disease Tool, collected by eDiary. Results: Patients (N=63) had a mean age of 72.8 years, and percent predicted post-bronchodilator forced expiratory volume in 1 second was 58.3%; 92% were male. Across 62 baseline sputum samples, microbiome composition was similar between 16S rRNA/metagenomic datasets. Patients graded Global Initiative for Chronic Obstructive Lung Disease (GOLD) III versus GOLD I/II had minimal differences in their microbial taxonomic profile and no differences in microbial diversity (Wilcoxon P=0.71). Alpha diversity (Shannon index) positively correlated with blood basophils (rho=0.41; P=0.0019) and negatively correlated with CAT score (rho=0.36; P=0.0069). Alpha diversity and sputum (rho: − 0.0637; P=0.7836) or blood (rho: 0.1739; P=0.2043) eosinophils were not correlated. No difference in alpha (P=0.5) or beta (P=0.3) diversity or Operational Taxonomic Unit (Anosim R=− 0.024; P=0.892) was observed between PPO-positive or -negative sputum. Conclusion: A less diverse microbiome correlated with poorer health status and lower blood basophils in patients with COPD and moderate airflow limitation. There was no relationship between PPO presence and microbiome diversity. Plain Language Summary: Chronic obstructive pulmonary disease (COPD) is a progressive lung condition resulting in breathing difficulties. Research has shown that patients with COPD experience changes in the diversity of bacteria in their lungs, leading to a worsening of symptoms. The lung microbiome includes different types of bacteria, and is involved in important roles, such as regulating the immune system and protecting the lung from invading pathogens. Many studies on the microbiome have been based in western countries, and there are few studies among Asian patients and populations with moderate COPD. The aim of this year-long study was to assess the diversity of the lung microbiome in Japanese patients with COPD and moderate airflow limitation, and how it affects patients’ immunity and disease severity. Patients’ sputum and blood samples were obtained at the start of the study and the different types of bacteria in the sputum and the number of immune cells in the blood were measured. Patients’ symptoms were also assessed at study start. Results showed that a less diverse lung microbiome was associated with lower levels of blood immune cells and worse COPD symptoms. These results improve our knowledge of the lung microbiome in an Asian population with COPD, providing insights into how lower bacterial diversity may worsen patient immunity and COPD severity.

Nucleos(t)ide analogue (NA) therapy is the current standard of care for chronic hepatitis B (CHB) virus infection but rarely achieves functional cure, necessitating long‐term therapy, which often leads to nonadherence and increased treatment burden. This retrospective cohort study was designed to describe treatment discontinuation and adherence to second‐generation NAs among patients with CHB in Japan. We used the Japanese Medical Data Center Claims Database (JMDC Inc.) to identify adults with CHB who were newly initiated on a single‐agent, second‐generation NA between January 2007 and August 2023. Outcomes included treatment discontinuation and adherence, treatment restart after discontinuation, NA switching and factors associated with treatment discontinuation/adherence. Of the 2473 patients included in this study (mean age 49.9 years), 65.6% were male. The most common index NAs were entecavir (55.5%) and tenofovir alafenamide fumarate (TAF, 36.2%). Treatment discontinuation was observed in 20.3% of patients; mean time to discontinuation was 20.4 months. Of the patients who discontinued, 50.7% restarted NAs. Mean adherence (proportion of days covered [PDC]) was 0.87, and 81.2% of participants had PDC ≥ 80%. Age group 35–64 years, index treatment TAF and baseline hepatocellular carcinoma diagnosis were significantly associated with a decreased probability of treatment discontinuation and nonadherence. Although a high proportion of patients were persistent and adherent to NA treatment, there is a subgroup of patients whose needs are not met while receiving NA treatment, particularly in younger age groups. The results emphasise the need for alternative therapies with shorter, finite treatment durations to improve patient persistence, adherence and outcomes.