NDM-1 (New Delhi metallo-beta-lactamase)

  • Medical Author:

    Sandra Gonzalez Gompf, MD, FACP is a U.S. board-certified Infectious Disease subspecialist. Dr. Gompf received a Bachelor of Science from the University of Miami, and a Medical Degree from the University of South Florida. Dr. Gompf completed residency training in Internal Medicine at the University of South Florida followed by subspecialty fellowship training there in Infectious Diseases under the directorship of Dr. John T. Sinnott, IV.

  • Medical Editor: Charles Patrick Davis, MD, PhD
    Charles Patrick Davis, MD, PhD

    Charles Patrick Davis, MD, PhD

    Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

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NDM-1 facts

  • NDM-1 stands for a gene that produces New Delhi metallo-beta-lactamase in certain bacteria that cause infections. This is a substance that destroys the commonest types of antibiotics.
  • Bacteria with the NDM-1 gene are part of a larger group of superbug bacteria that are extremely hard to treat and can spread easily in hospitals. Most NDM-1 strains are resistant to all commonly used antibiotics.
  • Specific testing for NDM-1 is not routinely available.
  • NDM-1 has been reported most commonly from India and Pakistan. It is spreading throughout the world as people travel from country to country.
  • The first three cases of NDM-1 in the United States were reported in June 2010.
  • NDM-1 is carried by bacteria that commonly inhabit the bowel. Strains spread from person to person through contact with contaminated hands or items.
  • Washing or disinfecting hands frequently and wearing protective clothing in hospitals lowers the risk of spreading or getting NDM-1. In hospitals, hand hygiene is critical. Patients with NDM-1 are also placed in private rooms, and health-care workers wear gowns and gloves when entering.
  • To reduce the risk of resistant bacteria, doctors and hospitals must use antibiotics wisely and only when needed.
  • Bacteria that express NDM-1 usually have other resistance factors, such as carbapenemases. Thus, most NDM-1 strains are resistant to all commonly used antibiotics.
  • Routine antibiotic-sensitivity testing can detect resistance to beta-lactam antibiotics. Specific testing for NDM-1 is not routinely available. Fortunately, it is not necessary to determine if carbapenem resistance is specifically due to NDM-1 because treatment is guided by the antibiotic-sensitivity testing.

What is NDM-1?

Antibiotics are medicines that kill bacteria (not viruses or fungi). There are different groups of antibiotics, based on how they work to kill bacteria. Beta-lactam antibiotics (or beta-lactams) are the largest group of antibiotics used against common infections. Carbapenems are another class of antibiotics typically used as a last resort when beta-lactams no longer work.

When bacteria are no longer killed by an antibiotic, they are called resistant to that antibiotic. Some bacteria are resistant to so many antibiotics there are few or no treatments left. These are often called "superbugs."

The beta-lactam group includes penicillins and cephalosporins. There are many types of beta-lactamases. Bacteria can become resistant by producing substances that destroy beta-lactams; these are beta-lactamases. The carbapenem antibiotics are destroyed by carbapenemases. Few bacteria have resistance to carbapenems. Carbapenems are often the last resort antibiotic for resistant bacteria that beta-lactams can no longer kill.

NDM-1 stands for the carbapenemase New Delhi metallo-beta-lactamase-1. It is produced by bacteria containing the resistance gene blaNDM-1. There are many types of carbapenemases that destroy penicillins, cephalosporins, and the last resort carbapenems, mostly produced by a large group of bacteria called Enterobacteriaceae. These carbapenemase-producers are also called carbapenem-resistant Enterobacteriaceae or CRE bacteria. NDM-1 bacteria are only one of the many CRE that threaten health today.

NDM-1 infection was first recognized in 2009, in residents or travelers from India and Pakistan. Antibiotic use in India is poorly restricted, and it appears likely that overuse of carbapenems allowed NDM-1 to develop. Medical tourism may cause NDM-1 to spread among countries. Medical tourism refers to people who travel to a country to get medical care that is not available or is more expensive in their own country. The three first cases of NDM-1 infection in the United States were identified in June 2010 in Americans who had recently sought medical care in India. Vacation and business travel have also played a role in introducing NDM-1 bacteria into countries outside of the Indian subcontinent. Cases have now been detected in many countries, including Great Britain, Canada, Sweden, Australia, Japan, and the United States. The number of cases is growing, and the concern is that these highly resistant bacteria could replace more antibiotic-susceptible strains. If this happens, many of the antibiotics that have been developed over the last 80 years will be useless. There are few new ways to kill bacteria that have not already been discovered, and it is feared that infections will return us to the days before antibiotics existed. Currently, NDM-1 bacteria are found mostly in health-care facilities, where antibiotics are used frequently. Therefore, these strains have also acquired resistance genes against other classes of antibiotics. These bacteria are true superbugs resistant to virtually all commonly used antibiotics.

NDM-1 and other resistant bacteria spread from person to person through contact with contaminated hands or items. Good hand hygiene is critical in hospitals to prevent the spread of bacteria and viruses. This includes washing hands with plain soap and water (antibacterial soap causes more resistance) or disinfecting hands with alcohol-based sanitizer.

Most NDM-1 strains must be treated with an older antibiotic called colistin, which had fallen out of use because it can be toxic to kidneys. Some strains may be treatable with the antibiotic aztreonam, or a newer one, tigecycline (Tygacil).

Although NDM-1 has gotten a lot of attention, other CREs with different enzymes have been identified and have spread. This includes the CRE Klebsiella pneumoniae species, also called KPC.

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What Is CRE?

CRE (carbapenem-resistant Enterobacteriaceae) bacteria are members of related bacterial genera that are commonly found almost everywhere in the world, often colonizing humans and animals (living in or on humans and animals mucosal surfaces, gastrointestinal tracts, and on some areas on the skin). However, CRE possess a unique genetic makeup that allows the bacteria to make an enzyme that protects CRE bacteria from a powerful antibiotic: carbapenem. The most notable genera that can share and even transfer this genetic trait to other members of the Enterobacteriaceae are E. coli and Klebsiella pneumoniae. Because these bacteria generate similar problems for patients (especially treatment difficulties), most investigators simply group them together and term them CRE bacteria (some researchers term those bacteria that produce the enzyme carbapenemase CP-CRE bacteria). Similar types of components are termed KPC (Klebsiella pneumoniae carbapenemase) and NDM (New Delhi metallo-beta-lactamase).

What causes NDM-1 to be produced in bacteria?

The blaNDM-1 gene has been found on bacterial chromosomes and plasmids. Plasmids are small segments of genetic material. Plasmids and other mobile genes can pass from one bacterial strain to another and even between completely different kinds.

Bacteria may develop gene mutations causing resistance spontaneously or on mobile genes. When a group of bacteria are exposed to an antibiotic, the ones that are resistant survive to multiply more of that bacteria. The more antibiotics are given, the more resistant bacteria are produced. This is called "antibiotic pressure" toward resistance. Reducing unnecessary antibiotic exposure allows populations of bacteria to revert to more susceptible strains.

What are symptoms and signs of a person infected with bacteria carrying NDM-1?

Bacteria from the Enterobacteriaceae family are the most common cause of urinary infections. They can also cause bloodstream infections (sepsis), pneumonia, or wound infections. Symptoms and signs depend on the location of the infection. Most people will have fever and fatigue and sometimes confusion. If bacteria enter the bloodstream, patients may go into shock. Symptoms do not differ between bacteria that express NDM-1 and those that do not. However, patients who have bacteria producing NDM-1 will not respond to most conventional antibiotics and are at high risk for complications or death.

How are bacteria that produce NDM-1 identified?

Laboratories routinely test bacteria for susceptibility to antibiotics. Strains that produce NDM-1 will show resistance to penicillins, cephalosporins, and carbapenems. Because carbapenem resistance is still uncommon, resistance to these agents raises suspicion of an NDM-1 or CRE strain, although not all will be NDM-1. If the patient has recently been to an area where NDM-1 is common, like India or Pakistan, this increases the probability that the strain is producing NDM-1.

Specific testing for NDM-1 is not routinely available in most laboratories. Fortunately, most NDM-1 or CRE are susceptible to colistin and other drugs. If a carbapenem-resistant isolate is recovered from a patient who has received medical care in India or Pakistan, it is sent to a state public-health laboratory. The state lab forwards it to the Centers for Disease Control and Prevention for specific testing for NDM-1, and the movement of these strains can be closely tracked.

What is the treatment for an infection caused by bacteria that make NDM-1?

Many NDM-1 infections will respond to treatment. Colistin is an older antibiotic that has not been used much in recent decades due to toxicity. A few NDM-1 strains have been sensitive to tigecycline (Tygacil), but this agent is not the first choice in serious infections, because it does not achieve high levels in the blood. Further, it only stops bacteria from multiplying, rather than destroying them. A few NDM-1s have been susceptible to aztreonam, although most U.S. strains have not. Research for new treatments is ongoing.

What is the prognosis for a person infected with NDM-1 producing bacteria?

NDM-1 infections can be successfully treated if they are recognized early and if colistin or other appropriate agents are used promptly. If a CRE infection is severe or the bacteria is aggressive, death is very possible. Death rate from KPC infections, for example, may be as high as 40%.

Is it possible to prevent infections with bacteria containing NDM-1?

Several major guidelines have been published about preventing resistant bacteria, and hospital accrediting organizations cannot accredit facilities that do not adhere to them. Hospital Infection Control programs monitor for resistant bacteria and use methods of blocking the spread of disease. Barriers between contaminated surfaces and health-care workers prevent transfer of bacteria from an infected patient to another patient or worker. Barriers for NDM-1 must be extremely strict to contain it. Patients with NDM-1 strains are placed in private rooms. Health-care workers must put on a gown and gloves when entering the room and carefully dispose of them in the room before leaving. The number of people caring for the patient, entering and leaving the room, and the patient's movements out of the room are minimized.

Antimicrobial Stewardship Programs are also critical to controlling resistant bacteria. Such programs help to ensure that antibiotics are used for the right reason, at the right dose, and for the minimum time necessary to treat bacterial infections. This may involve an infectious-disease doctor and pharmacist reviewing antibiotic use and providing personalized feedback to patients' doctors. Carbapenem antibiotics are only given intravenously and should only be used when bacteria are resistant to other drugs.

In the community, it is important that primary-care doctors and other health professionals prescribe antibiotics just as carefully. People should become informed about the pros and cons of antibiotics. Antibiotics do not kill viruses that cause most colds, ear and sinus infections, and bronchitis. They do kill friendly flora though, which can result in worse infections and antibiotic resistance. In addition, antibiotic allergies can be life-threatening; if you develop allergies to antibiotics because of overuse, it can reduce your options for treating serious infections even more than having an antibiotic-resistant bacterial infection.

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Where can people find more information about NDM-1 producing bacteria?

More information about NDM-1 is available from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

REFERENCES:

Kumarasamy, K.K., M.A. Toleman, T.R. Walsh, J. Bagaria, F. Butt, et al. "Emergence of a New Antibiotic Resistance Mechanism in India, Pakistan, and the UK: A Molecular, Biological, and Epidemiological Study." Lancet Infect Dis 10 (2010): 597-602.

United States. Centers for Disease Control and Prevention. "Detection of Enterobacteriaceae Isolates Carrying Metallo-Beta-Lactamase --- United States, 2010." MMWR 59.24 (2010): 750. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5924a5.htm>.

United States. Centers for Disease Control and Prevention. "Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care Facilities." MMWR 58.10 Mar. 20, 2009: 256-260. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5810a4.htm>.

Last Editorial Review: 9/23/2016

Reviewed on 9/23/2016
References
REFERENCES:

Kumarasamy, K.K., M.A. Toleman, T.R. Walsh, J. Bagaria, F. Butt, et al. "Emergence of a New Antibiotic Resistance Mechanism in India, Pakistan, and the UK: A Molecular, Biological, and Epidemiological Study." Lancet Infect Dis 10 (2010): 597-602.

United States. Centers for Disease Control and Prevention. "Detection of Enterobacteriaceae Isolates Carrying Metallo-Beta-Lactamase --- United States, 2010." MMWR 59.24 (2010): 750. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5924a5.htm>.

United States. Centers for Disease Control and Prevention. "Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care Facilities." MMWR 58.10 Mar. 20, 2009: 256-260. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5810a4.htm>.

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