Comprehensive Strategies for Prevention and Management of Antimicrobial Resistance in Respiratory Infections

Antimicrobial resistance (AMR) is recognised as one of the most critical public health challenges of the 21st century. If the current trajectory remains unaltered, projections indicate that by 2050, drug-resistant bacteria could result in 10 million fatalities annually [1]. Additionally, Smith et al. have highlighted that the global economic repercussions of AMR could amount to as much as 3.4 trillion US dollars per year by 2030 [2], underscoring the pressing need for interventions from a healthcare economics standpoint. Among the resistant bacteria that pose challenges in respiratory infections are penicillin-resistant Streptococcus pneumoniae (PRSP), multidrug-resistant Pseudomonas aeruginosa (MDRP), ampicillin-resistant strains of Haemophilus species [3, 4], and, more recently, the rising incidence of macrolide-resistant Mycoplasma pneumoniae [5]. The judicious use of antimicrobials not only preserves the efficacy of these medications but also mitigates unnecessary adverse effects and curtails the development of resistant bacteria. Most antimicrobial prescriptions in primary care clinics pertain to respiratory infections, rendering the appropriate use of antimicrobials crucial for advancing measures against AMR. When comparing respiratory infections with other infectious diseases, two significant distinctions emerged. First, the severity of respiratory infections is more frequently influenced by host-related factors, particularly advanced age and the presence of underlying conditions—rather than the pathogenicity of the infectious agent itself. For example, some exacerbations of chronic obstructive pulmonary disease are not attributable to bacterial infections, and aspiration pneumonia in older individuals cannot be effectively treated with antibiotics alone. Furthermore, domestic retrospective clinical studies and database research have demonstrated that broad-spectrum antibiotic use may exacerbate patient outcomes [6, 7]. Animal experiments have also indicated that prior administration of broad-spectrum antibiotics diminishes gut microbiota diversity and impairs immune function, resulting in significantly poorer outcomes in Pseudomonas aeruginosa pneumonia models [8]. Second, it is important to note that in respiratory infections, bacteria isolated from sputum cultures are not always the causative pathogens. Even when MRSA is isolated from sputum, true MRSA pneumonia is relatively rare [9]. As with the appropriate use of antimicrobials, the promotion of preventive medicine is extremely important. In older individuals, vaccination with pneumococcal and influenza vaccines is effective in preventing severe pneumonia [10]. Numerous studies have reported that oral care is effective for preventing aspiration pneumonia [11]. Therefore, its incorporation into routine clinical practice is strongly recommended. In 2016, Japan implemented the 'AMR Countermeasure Action Plan', which facilitated the monitoring of AMR through the Japan Nosocomial Infections Surveillance (JANIS) and the execution of educational initiatives by the AMR Clinical Reference Center. As of 2023, Japan is recognised as one of the world's leading super-aged societies with approximately 29.3% of the population above the age of 65. Within this demographic context, the challenges of pneumonia in older patients and AMR are closely connected. The Japanese Respiratory Society revised the risk factors for resistant bacteria in healthcare-associated and hospital-acquired pneumonia in the 2024 edition of the Adult Pneumonia Treatment Guidelines [12]. Previously, the guidelines judged the risk of resistant bacteria if patients met two or more of the following four criteria: (1) a history of intravenous antimicrobial use within the past 90 days, (2) a history of hospitalisation for two or more days during the same period, (3) immunosuppressed status, and (4) decreased activity level. However, this standard tended to overestimate the risk of antimicrobial-resistant bacteria. The new guidelines were revised so that among the seven factors (enteral nutrition, immunosuppressed status, history of antimicrobial use within 90 days, recent hospitalisation within 90 days, history of detection of resistant bacteria within 1 year, hypoalbuminemia, and mechanical ventilation by intubation), patients with non-severe cases are now considered at risk if three or more items are applied [12]. Additionally, the combined use of preventive interventions such as vaccination and oral care is recommended [12]. In addition, the Ministry of Health, Labour and Welfare recently established a 'Respiratory Infection Prevention Week' starting in 2024 (Figure 1). Through this initiative, activities such as the promotion of vaccinations and oral care for the older adults are being conducted in collaboration with local governments, with efforts advancing on a community scale. Conversely, Japan faces significant challenges regarding the supply of antibiotics within the framework of AMR countermeasures. In recent years, numerous antibiotics have encountered supply disruptions due to manufacturing process issues in factories located abroad, which have substantially impacted clinical practice. The primary reasons for these disruptions include reliance on foreign sources, particularly specific countries, for raw materials and precursors of antibiotics. This reliance is exacerbated by the declining profitability of Japanese manufacturers, attributed to stagnant drug prices. Consequently, companies find it increasingly difficult to maintain and upgrade production facilities, resulting in heightened supply instability. In 2019, a large-scale suspension of cefazolin injections occurred, causing confusion owing to a sudden surge in the demand for alternative drugs. In response, the Ministry of Health, Labour, and Welfare has implemented measures such as supporting the domestication of raw material production, partially raising drug prices, and making it mandatory to report supply status. However, as of 2025, supply restrictions remain in place for many drugs. Ensuring a stable supply of antibiotics is fundamental for infectious disease treatment and is an urgent issue from the perspective of medical safety. Going forward, the establishment of a sustainable supply system through collaboration among industry, government, and academia will be strongly required. Finally, in tackling AMR in respiratory infections, it is essential not only to use antibiotics appropriately but also to deepen our understanding of host factors. Furthermore, the promotion of preventive healthcare measures such as vaccination and oral care, as well as government-led structural responses to issues with antibiotic supply, is crucial. Healthcare professionals must adopt a multifaceted approach based on scientific evidence and actively collaborate with policymakers. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.