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

    NDM-1 facts

    • NDM-1 stands for New Delhi metallo-beta-lactamase, which is an enzyme that destroys beta-lactam antibiotics including the penicillins, cephalosporins, and carbapenems.
    • NDM-1 has been reported most commonly from India and Pakistan but 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.
    • Bacteria that express NDM-1 usually have other resistance factors. Most 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.
    • Most NDM-1 strains remain sensitive to an older, little-used antibiotic called colistin. Some strains have also been sensitive to tigecycline or aztreonam.
    • NDM-1 is carried by bacteria that commonly inhabit the bowel. Strains spread from person to person through contact with contaminated hands or items.
    • Good hand hygiene practices will reduce the risk of spreading or acquiring NDM-1. In hospitals, hand hygiene is critical and patients with NDM-1 should be placed in private rooms and health-care workers should used gowns and gloves when entering the room.
    • To reduce the risk that NDM-1 will arise, physicians and hospitals should ensure that antibiotics are used judiciously and appropriately.

    What is NDM-1?

    NDM-1 stands for New Delhi metallo-beta-lactamase, which is an enzyme produced by certain strains of bacteria that have recently acquired the genetic ability to make this compound. The enzyme is active against other compounds that contain a chemical structure known as a beta-lactam ring. Unfortunately, many antibiotics contain this ring, including the penicillins, cephalosporins, and the carbapenems.

    There are many types of beta-lactamases. Most are only active against older beta-lactam antibiotics but are not active against newer agents like the carbapenems. However, bacteria that produce NDM-1 are resistant to all commonly used beta-lactam antibiotics, including carbapenems. Some antibiotics like aminoglycosides and fluoroquinolones do not contain beta-lactam rings. Unfortunately, the bacteria that have acquired NDM-1 have also acquired other resistance factors and most are already resistant to aminoglycosides and fluoroquinolones. The addition of NDM-1 production has the ability to turn these bacteria into true superbugs (bacteria resistant to usually two or more antibiotics) which are resistant to virtually all commonly used antibiotics.

    NDM-1 infection was first identified (in 2009) in people who resided in or traveled to the India and Pakistan. Antibiotic use in India is not as restricted as it is in the United States and some researchers feel overuse of carbapenems allowed NDM-1 to develop. Others point to the advent of medical tourism as a cause of NDM-1 spread among countries. Medical tourism refers to patients 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.

    NDM-1 is a newly identified problem, only recognized since about December 2009 in the medical literature. To date, there have fewer than 100 cases identified outside of the Indian subcontinent, so this is not a pandemic like bird flu or swine flu. However, the number of cases is growing and the concern is that these highly resistant bacteria (bacteria carrying this NDM-1) could supplant more antibiotic-sensitive strains. If this happens, the antibiotic arsenal that has been built up over the last 80 years will be seriously compromised.

    What causes NDM-1 to be produced in bacteria?

    The gene that encodes for NDM-1 is called blaNDM-1 and has been identified on bacterial chromosomes and plasmids. Plasmids are small segments of genetic material that are easily transferred among bacteria. In this way, the ability to produce NDM-1 can pass from one bacterial strain to another and even from one bacterial genus to another.

    Cases of NDM-1 infection are usually caused by gram negative bacteria from the Enterobacteriaceae family. This family includes common bacteria like Escherichia coli (E. coli) and Klebsiella. These bacteria reside in the bowel and may spread from person to person if hands or items are contaminated with fecal material. To date, strains of Klebsiella, Escherichia, and Acinetobacter genera of bacteria are known to possess the gene for NDM-1.

    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 reflect the site of the infection. Most patients will have fever and fatigue. 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.

    How are bacteria that produce NDM-1 identified?

    It is standard practice to test bacteria for sensitivity to antibiotics. Strains that produce NDM-1 will show resistance to penicillins, cephalosporins, and carbapenems. Because carbapenem resistance is still relatively rare, resistance to these agents should raise suspicion of NDM-1, although not all of these resistant strains will be NDM-1 strains. 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 clinical laboratories. 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. If a carbapenem-resistant isolate is recovered from a patient who has received medical care in India or Pakistan, it should be sent to a state public-health laboratory, which will forward it to the Centers for Disease Control and Prevention for specific testing for NDM-1. Patients who have bacteria isolated from an infected site that produce NDM-1 are then definitively diagnosed as having an infection caused by bacteria that produce NDM-1.

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

    Treatment is guided by the antibiotic resistance pattern. Many NDM-1 strains are resistant to all antibiotics except for colistin and tigecycline. Colistin is an older antibiotic that has not been used much in recent decades, because it is somewhat more toxic than other antibiotics. A few NDM-1 strains have been sensitive to tigecycline (Tygacil), but this agent should be used cautiously in serious infections because it does not achieve high levels in the bloodstream. A few strains have also been sensitive to aztreonam, although the U.S. strains were not. Researchers have identified a new antibiotic compound that may inhibit NDM-1 containing bacterial topoisomerase function so the bacterial replication is inhibited or stopped. Unfortunately, the compound has not gone through any clinical trials and is not commercially available.

    Learn more about: Tygacil

    Learn more about: Tygacil

    What causes NDM-1 to be produced in bacteria?

    The gene that encodes for NDM-1 is called blaNDM-1 and has been identified on bacterial chromosomes and plasmids. Plasmids are small segments of genetic material that are easily transferred among bacteria. In this way, the ability to produce NDM-1 can pass from one bacterial strain to another and even from one bacterial genus to another.

    Cases of NDM-1 infection are usually caused by gram negative bacteria from the Enterobacteriaceae family. This family includes common bacteria like Escherichia coli (E. coli) and Klebsiella. These bacteria reside in the bowel and may spread from person to person if hands or items are contaminated with fecal material. To date, strains of Klebsiella, Escherichia, and Acinetobacter genera of bacteria are known to possess the gene for NDM-1.

    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 reflect the site of the infection. Most patients will have fever and fatigue. 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.

    How are bacteria that produce NDM-1 identified?

    It is standard practice to test bacteria for sensitivity to antibiotics. Strains that produce NDM-1 will show resistance to penicillins, cephalosporins, and carbapenems. Because carbapenem resistance is still relatively rare, resistance to these agents should raise suspicion of NDM-1, although not all of these resistant strains will be NDM-1 strains. 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 clinical laboratories. 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. If a carbapenem-resistant isolate is recovered from a patient who has received medical care in India or Pakistan, it should be sent to a state public-health laboratory, which will forward it to the Centers for Disease Control and Prevention for specific testing for NDM-1. Patients who have bacteria isolated from an infected site that produce NDM-1 are then definitively diagnosed as having an infection caused by bacteria that produce NDM-1.

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

    Treatment is guided by the antibiotic resistance pattern. Many NDM-1 strains are resistant to all antibiotics except for colistin and tigecycline. Colistin is an older antibiotic that has not been used much in recent decades, because it is somewhat more toxic than other antibiotics. A few NDM-1 strains have been sensitive to tigecycline (Tygacil), but this agent should be used cautiously in serious infections because it does not achieve high levels in the bloodstream. A few strains have also been sensitive to aztreonam, although the U.S. strains were not. Researchers have identified a new antibiotic compound that may inhibit NDM-1 containing bacterial topoisomerase function so the bacterial replication is inhibited or stopped. Unfortunately, the compound has not gone through any clinical trials and is not commercially available.

    Learn more about: Tygacil

    Learn more about: Tygacil

    Source: http://www.rxlist.com

    Treatment is guided by the antibiotic resistance pattern. Many NDM-1 strains are resistant to all antibiotics except for colistin and tigecycline. Colistin is an older antibiotic that has not been used much in recent decades, because it is somewhat more toxic than other antibiotics. A few NDM-1 strains have been sensitive to tigecycline (Tygacil), but this agent should be used cautiously in serious infections because it does not achieve high levels in the bloodstream. A few strains have also been sensitive to aztreonam, although the U.S. strains were not. Researchers have identified a new antibiotic compound that may inhibit NDM-1 containing bacterial topoisomerase function so the bacterial replication is inhibited or stopped. Unfortunately, the compound has not gone through any clinical trials and is not commercially available.

    Source: http://www.rxlist.com

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