CARBAPENEMASES ARE carbapenem-hydrolyzing beta-lactamases produced by some bacteria that allow them to become resistant to penicillins, cephalosporins (such as cefazolin, cefuroxime, ceftriaxone, and cefepime), and carbapenems (such as imipenem, meropenem, ertapenem, and doripenem). These antibiotics are used to treat life-threatening infections, and increased resistance to them is a worldwide problem.1
A new form of carbapenemase that's highly resistant to antibiotics and easily transmitted has recently been identified: New Delhi metallo-beta-lactamase-1 (NDM-1). It was first described in a Swedish patient who contracted a Klebsiella pneumoniae infection while in India in late 2007.2 It was first thought to be a nosocomial pathogen limited to hospitals in India. Since then, environmental studies in India have shown widespread contamination by NDM-1-encoded bacteria that's circulating in the community as well as healthcare settings.2
NDM-1 isn't the first carbapenemase to be identified. K. pneumoniae carbapenemases (KPCs) were discovered in 1996 in the eastern United States and spread globally within 5 years.1 In contrast to KPCs, the NDM-1 gene has several characteristics that are deeply concerning for public health worldwide.
NDM-1 is carried on a part of bacterial DNA that allows easy transmission among organisms, giving it the potential to spread quickly.3 Although NDM-1 is found mostly in K. pneumoniae and Escherichia coli, it's also been detected in other bacteria that are part of our normal gut flora.3 These bacteria can cause a wide range of infections, such as wound, respiratory, bloodstream, and urinary tract infections.
Increasing human air travel and migration allow strains of bacteria carrying NDM-1 to disseminate across the world when it's carried in normal human flora.3 The Indian medical tourism industry is growing: 350,000 patients were expected to visit India in 2010 and 2011 to fulfill their medical needs.4 In the United States, three NDM-1 cases linked to travel in India have been reported.5 Besides India and the United States, NDM-1 has also been reported in Pakistan, the United Kingdom, Europe, Canada, Australia, Japan, and Vietnam.5
Antimicrobial resistance has become a global public health and environmental catastrophe. It's particularly concerning in countries where antimicrobials can be purchased over the counter, as in India, China, Africa, and Central and South America.5
In 2001, the World Health Organization (WHO) launched a strategy to curb antibiotic resistance. The recommendations included banning the use of nonprescribed antibiotics, initiating prudent antibiotic formularies in hospitals, implementing stringent infection control policies, establishing national surveillance programs, and collaborating with international groups for better understanding of antibiotic resistance.6 Unfortunately, the WHO campaign coincided with the September 2001 terrorist attacks, which overshadowed the release and implementation of campaign initiatives.5
What you can do
The CDC recommends an aggressive infection control strategy to prevent the spread of NDM-1. Facilities should review their microbiology records for the preceding 6 to 12 months. If NDM-1 is identified, perform a single round of active surveillance testing in high-risk units to look for new cases of NDM-1. High-risk units include the ICU, units where previous cases have been identified, or units where patients are exposed to broad-spectrum antibiotics. Other risk factors include use of broad-spectrum cephalosporins and/or carbapenems, mechanical ventilation, diabetes, trauma, malignancy, organ transplantation, overall poor functional status, and having received medical care in India or Pakistan.7
Consider isolating a patient if he or she doesn't improve with the current antibiotic therapy and lab cultures reveal bacteria that are antibiotic resistant. Active surveillance cultures of stool or rectal swabs can be tested for NDM-1. If patients are identified as NDM-1-positive, the CDC recommends they be placed on contact precautions. Active surveillance cultures should be performed on other patients with links to the positive patient, such as patients in the same room or unit.8 Hand hygiene using alcohol-based hand rubs or soap and water are essential for interrupting transmission.
Only two current antibiotic drugs can combat NDM-1. Many bacteria carrying NDM-1 are susceptible only to tigecycline and colistin.1 Colistin causes renal toxicity in about one-third of patients, and tigecycline is of unproven efficacy in severe infections.4,5
Meticulous adherence with standard precautions, including hand hygiene and environmental cleaning and disinfecting with hospital-grade cleaners, is needed to prevent transmission of this newest “superbug.”
1. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis
2. Walsh TR, Weeks J, Livermore DM, Toleman MA. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect Dis
3. Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis
4. Kaul TK, Chhina DK. Medical tourism and New Delhi metallo-beta-lactamase 1: a concern and threat. J Anaesthesiol Clin Phamacol
5. Conly J. Antimicrobial resistance: revisiting the “tragedy of the commons.” Bull World Health Organ
6. Walsh TR, Toleman MA. The new medical challenge: why NDM-1? Why Indian? Expert Rev Anti Infect Ther
8. CDC Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities. MMWR Morb Mortal Wkly Rep