3,Most Critical Antimicrobial-Resistant Bacteria

Hospital-Acquired Bacteria of Greatest Concern in Japan

1. MRSA (Methicillin-Resistant Staphylococcus aureus)

• Representative causative pathogen of hospital-acquired infections in Japan

• According to JANIS data, approximately 50-60% of Staphylococcus aureus isolates are MRSA

• Particularly serious problem in elderly care facilities

2. Multidrug-Resistant Pseudomonas aeruginosa (MDRP)

・Problematic infections in intensive care units　　　・Cause of severe infections with high mortality rates

3. Carbapenem-Resistant Enterobacteriaceae (CRE)

・Increasing trend in recent years　　　　　　　 　・Extremely limited therapeutic options

Hospital-Acquired Bacteria of Greatest Concern in the United States

CDC "Urgent Threats" (Highest Alert Level)

1. Clostridioides difficile (C. diff)

・Approximately 29,000 deaths annually　　　　　　　・Primary cause of antibiotic-associated diarrhea

2. Carbapenem-Resistant Enterobacteriaceae (CRE)

・Approximately 1,100 deaths annually　　　　　　　 ・High fatality rate with about 50% of infected patients dying

3. Drug-Resistant Gonorrhea

• Primarily sexually transmitted, but hospital-acquired mother-to-child transmission is also a concern

CDC "Serious Threats"

・MRSA: Approximately 10,600 deaths annually (significant decrease from peak levels)

・Multidrug-Resistant Acinetobacter　　　　　　　　・Multidrug-Resistant Pseudomonas aeruginosa

Numerical Data

United States (CDC Data)

• Annual deaths from hospital-acquired infections: approximately 75,000 people

• Annual increase in healthcare costs: approximately $20-35 billion

• Average hospital stay extension due to MRSA infection: 7-10 days

Japan

• While JANIS data provides detailed resistance rates, accurate statistics on deaths are limited

• Estimated economic loss due to antimicrobial-resistant bacteria: approximately 800 billion yen annually

Important Trends

• In the United States, MRSA has been declining in recent years, with C. diff and CRE being the most critical issues

• In Japan, MRSA remains a major problem, with increasing concern about CRE​

Comparison of Policies and Countermeasures

US National Strategy

National Action Plan (2020-2025):

・Establishment of CARB (Combating Antibiotic Resistant Bacteria)　　・Annual budget allocation of $1.2 billion

・One Health approach　　　　　　　　　　　　　　　　　　　　　 ・CDC-led surveillance enhancement

Major Programs:

・Mandatory Antibiotic Stewardship Programs　　　　　・NHSN (National Healthcare Safety Network)

・Establishment of CDC's AR Lab Network　　　　　・Promotion of IDSA/SHEA guideline compliance

Japan's National Strategy

AMR Action Plan (2023-2027):

・Cross-ministerial framework led by the Cabinet Secretariat　　・Annual budget of approximately 5 billion yen

• J-SIPHE (Japan Surveillance for Infection Prevention and Healthcare Epidemiology)

• Expansion of JANIS (Japan Nosocomial Infections Surveillance)

Major Initiatives:

・Infection Control Specialist Pharmacist System

・Establishment of antimicrobial stewardship support reimbursement

・AMR Clinical Reference Center establishment　・Construction of evaluation system within medical fee schedule

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​４、Why Are Infectious Diseases Considered an Eternal Challenge for

　　　　Humanity?

１、Biological Characteristics of Pathogens 

• High adaptability: Pathogens rapidly adapt and evolve in response to environmental changes

• Speed of mutation: Particularly viruses generate new strains through genetic mutations

• Acquisition of drug resistance: Pathogens acquire resistance to antibiotics and other treatments, making therapy difficult

２、Characteristics of Infection Spread 

• Exponential growth: Rapid spread from one person to multiple individuals

• Asymptomatic carriers: Infection can spread even without symptoms

• Globalization: Human and goods movement enables worldwide spread within short periods

３、Limitations of Prevention and Treatment 

• Difficulty of complete prevention: No preventive measures exist with 100% efficacy

• Emerging infectious diseases: New threats from unknown pathogens appear periodically

• Vaccine development time: Developing vaccines against new infectious diseases requires significant time

４、Socioeconomic Factors 

• Sanitation disparities: Differences in sanitary conditions across regions and social strata

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5、　The U.S. EPA approved copper alloys as continuous antimicrobial agents

　　　in 2008.

1. Innovation of the Copper Alloy Approach 

Significance of EPA Approval

• 2008 EPA Approval: First-ever certification of continuous antimicrobial activity for solid surface materials

• Contact Disinfection: Physical contact-based disinfection rather than pharmaceutical administration

• MRSA, VRE, etc.: Clinical demonstration of effectiveness against multidrug-resistant bacteria

2. Important Insights from This Approach 

Resistance Avoidance Mechanism

• Conventional: Biological targets → resistance acquisition possibl

• Copper Alloys: Physicochemical destruction → resistance acquisition difficult

Multi-target Simultaneous Attack

• Cell membrane destruction • Enzyme function inhibition • DNA damage • Respiratory chain inhibition ​　　　　　　　　　　　　　　　　Since these occur simultaneously, resistance acquisition is extremely difficult

3. New Paradigm Demonstrated by the Copper Alloy Approach 

Shift from "Pharmaceuticals" to "Environment"

• Old Paradigm: Post-infection pharmaceutical treatment

• New Paradigm: Creating environments that prevent infection

Fundamental Solution to Antibiotic Resistance Problems

• Avoidance of Evolutionary Pressure: Physical attacks to which bacteria cannot adapt

• Prevention Priority: Strategic shift from treatment to prevention

• Sustainability: Solutions with long-lasting effectiveness

4. Future Challenges

• Biocompatibility optimization • Avoidance of local toxicity • Selective disinfection (protection of resident flora) • Cost and versatility