New Delhi Metallo-Beta-Lactamase (NDM) Infections

Introduction to NDM

• NDM (New Delhi metallo-beta-lactamase) is a metallo-β-lactamase enzyme first identified in 2007 in a patient who had been hospitalized in New Delhi, India 1
• NDM enzymes are typically encoded on plasmids (mobile genetic elements) that can be easily transmitted between different bacterial species 1

Epidemiology of NDM

• NDM-producing bacteria have been identified worldwide with highest prevalence in the Indian subcontinent 2
• International travel and hospitalization in endemic regions are significant risk factors 3
• In the United States, NDM cases are still relatively rare but increasing 1, 3

Clinical Significance of NDM

• NDM-producing bacteria can cause various infections including urinary tract infections 4, bloodstream infections 5, pneumonia 4, and wound infections 1, 3
• Most NDM-producing isolates are only susceptible to limited antibiotics such as tigecycline 4, colistin 4, and polymyxin B 1, 3

Treatment Options for NDM

• For infections caused by metallo-β-lactamase (MBL)-producing CRE, including NDM, ceftazidime/avibactam plus aztreonam should be preferred as first-line therapy 6, 5
• Cefiderocol may also be considered as an alternative option 6
• Combination therapy is often required for severe infections 6

Infection Control Measures

• Aggressive infection control measures are essential to prevent spread 1, 3
• Key infection control strategies include contact precautions (gowns and gloves) for all patient care 3, dedicated medical equipment 2, enhanced environmental cleaning 3, 2, point-prevalence surveys of epidemiologically linked patients 3, active surveillance in high-risk units 2, and limiting unnecessary antibiotic exposure through antimicrobial stewardship 2

Public Health Implications

• U.S. and international efforts to control carbapenem-resistant Enterobacteriaceae (CRE) are critical to protect public health 1
• Patients with history of NDM colonization or infection should have their medical records flagged for future admissions 4
• Healthcare facilities should avoid exposing wounds, injection sites, and catheters to tap water, as water systems can harbor these organisms 2

NDM Infection Characteristics and Treatment

Enzyme Classification and Resistance

• NDM belongs to Class B metallo-β-lactamases (MBLs) in the Ambler classification system, alongside other MBLs such as VIM and IMP 7, 8
• NDM-producing bacteria are particularly worrisome due to their ability to hydrolyze all classes of β-lactams and the inability of classic serine β-lactamase inhibitors to inhibit them 7

Diagnostic and Treatment Considerations

• Rapid testing should be used to identify specific carbapenemase families (including NDM) in carbapenem-resistant Enterobacterales (CRE) to guide appropriate treatment 7, 9
• Knowledge of the molecular mechanism responsible for carbapenem resistance is crucial because each class of enzymes confers variable susceptibility profiles requiring different treatment strategies 8

NDM Prevalence and Distribution

Global Distribution Patterns

• High-income countries, as reported by the World Health Organization, generally have lower prevalence of NDM-producing bacteria compared to endemic regions, though surveillance systems in these countries are more robust 10
• Underdeveloped countries likely have significant underreporting of NDM-producing bacteria due to limited surveillance systems and diagnostic capabilities, meaning the true global prevalence is likely higher than documented, according to the Centers for Disease Control and Prevention 11

Clinical Implications of Geographic Variation

• Knowledge of regional resistance patterns is essential for empirical treatment decisions, as emphasized by the Infectious Diseases Society of America, for managing infections in areas with varying NDM prevalence 12
• The World Health Organization recommends that knowledge of regional resistance patterns is crucial for empirical treatment decisions, and this is supported by evidence from the World Journal of Emergency Surgery 10