What is NDM (New Delhi Metallo-beta-lactamase)?
NDM is a metallo-β-lactamase enzyme that hydrolyzes nearly all β-lactam antibiotics including carbapenems, making it one of the most concerning antimicrobial resistance mechanisms worldwide. 1
Enzyme Classification and Mechanism
- NDM belongs to Class B metallo-β-lactamases (MBLs) in the Ambler classification system, alongside other MBLs such as VIM and IMP 1
- The enzyme uses a zinc ion-dependent catalytic mechanism to break down β-lactam antibiotics 2, 3
- Classic serine β-lactamase inhibitors (like clavulanic acid or tazobactam) cannot inhibit NDM because of its distinct metalloenzyme structure 1
- NDM can hydrolyze all classes of β-lactams, including penicillins, cephalosporins, and carbapenems 4, 2
Genetic and Transmission Characteristics
- NDM genes are typically encoded on plasmids (mobile genetic elements) that can be easily transmitted between different bacterial species 1
- These plasmids often carry multiple resistance genes, conferring multi-drug resistance to the host organism 4, 5
- Over 24 NDM variants have been identified, with some variants showing enhanced carbapenemase activity 4, 6
- The enzyme has been identified in more than 60 bacterial species across 11 bacterial families 4
Bacterial Hosts and Clinical Impact
- Klebsiella pneumoniae and Escherichia coli are the predominant carriers of NDM genes 4
- Specific high-risk sequence types include ST11, ST14, ST15, and ST147 for K. pneumoniae; ST167, ST410, and ST617 for E. coli 4
- NDM-producing bacteria cause various infections including urinary tract infections, bloodstream infections, pneumonia, and wound infections 1
- These organisms can cause both nosocomial and community-acquired infections 2
Geographic Distribution and Epidemiology
- NDM was first identified in 2007 in a patient hospitalized in New Delhi, India 1
- Highest prevalence occurs in the Indian subcontinent, Middle East, and Balkans 4
- International travel and hospitalization in endemic regions are significant risk factors for acquisition 1
- In the United States, NDM cases remain relatively rare but are increasing, including in ambulatory healthcare settings like hemodialysis centers 1, 3
Treatment Challenges
- Most NDM-producing isolates are only susceptible to limited antibiotics such as tigecycline, colistin, and polymyxin B 1
- For infections caused by NDM-producing bacteria, ceftazidime/avibactam plus aztreonam is the preferred first-line therapy, with 30-day mortality of 19.2% versus 44% with other therapies 7, 8
- Cefiderocol may be considered as an alternative option 1, 7
- No specific NDM inhibitors have been approved for clinical use despite ongoing research efforts 5
Detection Methods
- Phenotypic tests like combined disc test (CDT) and modified carbapenem inactivation method (mCIM) can detect carbapenemase activity 9
- Genotypic tests including RT-PCR and loop-mediated isothermal amplification (LAMP) provide rapid and accurate detection 9
- Lateral flow immunoassays can specifically detect NDM, while molecular approaches remain the reference standard 4
Infection Control Imperatives
- Aggressive infection control measures are essential, including contact precautions with gowns and gloves for all patient care 1
- Dedicated medical equipment should be used for affected patients 1
- Enhanced environmental cleaning and point-prevalence surveys of epidemiologically linked patients are critical 1
- Healthcare facilities should avoid exposing wounds, injection sites, and catheters to tap water, as water systems can harbor these organisms 1
- Patients with history of NDM colonization or infection should have their medical records flagged for future admissions 1