NDM-1

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Status Brief
History/Origins:

Developmental Milestones/Developments to Date:

Current Assessment/State of the Field:

Problems/Challenges:

Proposals:

2001

Gallagher, James, “NDM-1 Superbug Enzymes ‘Photo fit’ Taken,BBC News, September 6, 2001 http://www.bbc.co.uk/news/health-14788046 Last Checked 9/6/2011

  1. “The structure of the protein which stops some of medicine’s most powerful antibiotics working has been determined by researchers.”
  2. “The protein has larger ‘jaws’ which allow it to attack more antibiotics than other enzymes.” *”Carbapenem antibiotics are considered the last line of defense against resistant bacteria. However, some are now resistant even to these drugs.”
  3. “Bacteria with a gene for New Delhi metallo beta lactamase (NDM-1) are able to produce an enzyme which breaks antibiotics down.”
  4. “The way bacteria freely exchange genes between themselves, and even between species, means this resistance gene could spread to other disease-causing bacteria.”
  5. “Professor Sharon Peacock, a member of the Medical Research Council Infections and Immunity Board, said: ‘identifying the structure of NDM-1 is a crucial step towards ensuring that drug development is based on a sound understanding of the mechanism of bacterial resistance to antibiotics.’”

NDM-1, Drug Resistance, India

2010

Raghunath, D., “New Metallo β-lactamase NDM-1”, Published November 2010, Indian Journal of Medical Research, Vol. 132 Issue 5, pg.478-481.

  1. “The métallo ß-lactamases (MBL) are the more versatile enzymes that can convert the host bacteria into almost total ß-lactam insusceptibil.” (pg.478)
  2. “The first bacterial isolate carrying the MBL later designated blaNOM-1 was a Klebsiella pneumonia urinary isolate from a patient with insignificant bacteria along with other multi-resistant bacteria from wound swabs.” (pg.478)
  3. “The NDM-1 gene is normally carried on a variety of plasmids along with other resistance factors. The bacteria also showed broad antibiotic resistance to all classes except colistin and ciprofloxacin.” (pg.478)
  4. “Rarely the gene was integrated into the chromosome. The sequencing of the gene showed that it was a new enzyme unrelated to hitherto known MBLs.” (pg.478)
  5. “NDM-1 confers on its host bacteria almost all ß lactam resistance and is accompanied by extensive antibiotic resistance. Such bacteria would be difficult to eliminate in clinical situations.” (pg.478)
  6. “Briefly, blaNDM-1 is a novel MBL with ability to confer resistance to almost all the ß lactams.” (pg.478)
  7. “A number of isolates from nine locations in India, eight cities in Pakistan and Dhaka, Bangladesh have been confirmed to carry NDM-1 (by PCR) indicating that the plasmid is perhaps quite widely distributed in the subcontinent. While this fact leads credence to the ‘Indian’ origin, it may not be necessarily so.” (pg.478)
  8. “However, the statement blaNDM-1 is widespread in the Indian environment is true.” (pg.479)
  9. “A heated debate in Indian professional and media circles is the assertion of the authors that patients from the West who would travel to the Indian sub-continent for elective surgery are at risk of post-operative infections due to bacteria carrying NDM-l resulting in higher treatment costs.” (pg.479)
  10. “This would negate any economy that would accrue to the NHS from contracted outsourcing of elective surgery to ‘countries such as India’.” (pg.479)
  11. “Septicaemia caused by a bacterium carrying NDM-1 would be well nigh impossible to treat if it has the accompanying resistances. However, the mere presence of the organism in the environment would not translate to infection if control measures are in position, as they would be, in the major corporate hospitals that cater to medical tourism.” (pg.479)
  12. “The National (UK) Resistance Alert in vol 3 (4) of the Health Protection Report (referred to 28) in this paper warns about carbapenemases but does not mention about the MBL blaNDM-1. However, a fresh alert specifically mentioning blaNDM-1 has been issued on July 3, 2009.” (pg.479)
  13. “There has been little evidence of clonal spread of NDM-1 bearing E.coli or K.pneumoniae except in the case of the isolates within Haryana.” (pg.479)
  14. “The epidemiology of the focus has not been systematically studied either. This needs to be done soon.” (pg.479)
  15. “The prescription habits, lack of infection control and easy access to even top line antibiotics add up to a dismal scenario prompting observers to write an ‘obituary’ to antibiotic treatment.” (pg.479)
  16. “These factors along with poor sanitation and personal hygiene foster the generation of resistant bacteria and their dissemination.” (pg.480)
  17. “The belief that multi-resistant pathogens are physically hampered and incapable of surviving in nature is no longer valid. Numerous instances of hospital generated or strains acclimatized to high levels of environmental antibiotic pressures living and spreading ‘merrily’ in the community are now known.” (pg.480)

NDM-1, India, Drug Resistance

 

Editors, “Detection of ”Enterobacteriaceae” Isolates Carrying Metallo-Beta-Lactamase — United States, 2010,” MMWR Morbidity and Mortality Weekly Report, Vol. 59, No. 24, CDC, Published June 25,2010.

  1. “Current CDC infection control guidance for carbapenem-resistant ”Enterobacteriaceae” also is appropriate for NDM-1–producing isolates (5). This includes recognizing carbapenem-resistant ”Enterobacteriaceae” when cultured from clinical specimens, placing patients colonized or infected with these isolates in contact precautions, and in some circumstances, conducting point prevalence surveys or active-surveillance testing among other high-risk patients. Laboratory identification of the carbapenemresistance mechanism is not necessary to guide treatment or infection control practices but should instead be used for surveillance and epidemiologic purposes.”
  2. “Current CDC infection control guidance for carbapenem-resistant Enterobacteriaceae also is appropriate for NDM-1–producing isolates.”
  3. “Carbapenem resistance and carbapenemase production conferred by blaNDM-1 is detected reliably with phenotypic testing methods currently recommended by the Clinical and Laboratory Standards Institute (3), including disk diffusion testing and the modified Hodge test.”
  4. “Clinicians should be aware of the possibility of NDM-1–producing ”Enterobacteriaceae” in patients who have received medical care in India and Pakistan, and should specifically inquire about this risk factor when carbapenem-resistant ”Enterobacteriaceae” are identified. CDC asks that carbapenem-resistant isolates from patients who have received medical care within 6 months in India or Pakistan be forwarded through state public health laboratories to CDC for further characterization. Infection control interventions aimed at preventing transmission, as outlined in current guidance (5), should be implemented when NDM-1–producing isolates are identified, even in areas where other carbapenem-resistance mechanisms are common among ”Enterobacteriaceae”.

NDM-1, Public Health, CDC

 

Hope, Jenny.Alarm over ‘unbeatable’ enzyme that could make all bacterial diseases resistant to antibioticsMail Online. August 12, 2010.
http://www.dailymail.co.uk/health/article-1302035/Unbeatable-NDM-1-enzyme-make-bacterial-diseases-superbugs.html

  1. “So far two types of bacteria have been host to NDM-1 –  the gut bug E.coli and another that can invade the lungs called Klebsiella pneumonia. Both can lead to urinary tract infections and blood poisoning.”
  2. “Figures suggest it costs between £500 million to £1 billion to bring new drugs to market.”
  3. “The NDM-1 gene alters bacteria”
  4. “Christopher Thomas, professor of molecular genetics at the University of Birmingham who was not linked to the study, said ‘We are potentially at the beginning of another wave of antibiotic resistance, though we still have the power to stop it.’”
  5. “’The consequences will be serious if family doctors have to treat infections caused by these multi-resistant bacteria on a daily basis’ he added.”
  6. “’Hospitals need to ensure they continue to provide good infection control to prevent any spread, consider whether patients have recently been treated abroad and send samples to the HPA for testing.’”

NDM-1, Pakistan

 

Editors. “New superbug now in Canada ‘Potentially a major global health problem,’ author of study says”  The Toronto Star. August 12, 2010.

  1. “Both Canadians, one in Alberta and one in B.C., infected by the antibiotic-resistant NDM-1 have recovered, but “we don’t know if the infection will come back,” Dr. Johann Pitout of the University of Calgary told the Star on Wednesday.”
  2. “Ages of the infected people ranged from 4 to 66, and the reasons for hospitalization included bone-marrow transplants, dialysis, heart disease, pregnancy, traffic accidents, burns and cosmetic surgery.”
  3. “”And as a result, with the patient being isolated and so on, there was no further spread of infection to anyone else in the hospital,” he said”

NDM-1, Pakistan

 

Editors. “Health authorities on alert for drug-resistant bacteriaThe Irish Times. August 12, 2010.

  1. “The more and more antibiotics that are used, the more likely the bugs are going to develop resistance in their quest to survive, she added.”
  2. “Good antibiotic prescribing along with basic hygiene control measures like hand washing and sterilisation remains the most effective way of preventing the spread of such bacteria, she said.”

NDM-1

 

Cooper, Charles. “Controversy over NDM-1 ‘Superbug’ Ignites Uproar in IndiaCBS News. August 13, 2010.
http://www.cbsnews.com/8301-501465_162-20013644-501465.html

  1. “It (superbug) is universal and is found in the intestine of humans and animals.”
  2. “Meanwhile, AFP is reporting the first NDM-1-related death, an unidentified Belgian man who was treated in Pakistan following an automobile accident.”
  3. “The threat of the NDM-1 is not that big as, say, H1NI (swine flu),the popular press has since deemed it.”

NDM-1

 

Associated Press, “NDM-1, Superbug Gene, Could Spread Worldwide, Doctors Warn,” September 6, 2010
http://www.huffingtonpost.com/2010/08/11/ndm-1-new-superbug-gene-c_n_678427.html

  1. “People traveling to India for medical procedures have brought back to Britain a new gene that allows any bacteria to become a superbug, and scientists are warning this type of drug resistance could soon appear worldwide.”
  2. “Though already widespread in India, the new superbug gene is being increasingly spotted in Britain and elsewhere. Experts warn the booming medical tourism industries in India and Pakistan could fuel a surge in antibiotic resistance, as patients import dangerous bugs to their home countries.”
  3. “The superbug gene, which can be swapped between different bacteria to make them resistant to most drugs, has so far been identified in 37 people who returned to the U.K. after undergoing surgery in India or Pakistan.”
  4. “The resistant gene has also been detected in Australia, Canada, the U.S., the Netherlands and Sweden.”
  5. “The gene alters bacteria, making them resistant to nearly all known antibiotics.”

NDM-1, Public Health

 

Associated Press,Austria reports 2 cases of superbug gene,” September 6, 2010 http://www.google.com/hostednews/ap/article/ALeqM5iJg9vxJttMtWFhClPLSt6Ay8zHHQD9HRNRR80

  1. “The ministry says experts at the medical university in the southern city of Graz detected the gene, known as NDM-1, in two people, both of whom are believed to have been infected in hospitals abroad.”

NDM-1, Public Health, Australia

 

Shino Yuasa, “Japan confirms its first case of new superbug gene,” AP September 7, 2010 http://news.yahoo.com/s/ap/20100907/ap_on_sc/as_japan_superbug

  1. “Japan has confirmed the nation’s first case of a new gene in bacteria that allows the microorganisms to become drug-resistant superbugs, detected in a man who had medical treatment in India, a Health Ministry official said Tuesday.”
  2. “The WHO says NDM-1 requires monitoring and further study. With effective measures, countries have successfully battled multi-drug resistant microorganisms in the past.”
  3. “It recommends that governments focus their efforts in four areas: surveillance, rational antibiotic use, legislation to stop sales of antibiotics without prescription, and rigorous infection prevention measures such as hand-washing in hospitals.”
  4. “Researchers say since many Americans and Europeans travel to India and Pakistan for elective procedures like cosmetic surgery, it was likely the superbug gene would spread worldwide.”
  5. “President of Indian Association of Medical Microbiology Dr Abhay Chaudhary, said, “Drug-resistant bacteria are not new. Whenever we use a particular antibiotic, bacteria will always try to develop resistance to it. This is a natural phenomena.””
  6. “”The potential of NDM-1 to be a worldwide public health problem is great, and coordinated international surveillance is needed,” said a widely publicised report in the Lancet in August, which pinpointed India as the country of origin.”

NDM-1, Public Health, WHO

 

Ebscohost. “Germ beats ‘last resort’ antibiotics“. USA TODAY, Sept. 17, 2010.
http://www.usatoday.com/printedition/news/20100917/1asuperbug17_st.art.htm

  1. “Bacteria that are able to survive every modern antibiotic are cropping up in many U.S. hospitals and are spreading outside the USA, public health officials say.”
  2. “The bugs, reported by hospitals in more than 20 states, typically strike the critically ill and are fatal in 30% to 60% of cases”
  3. “The bacteria are equipped with a gene that enables them to produce an enzyme that disables antibiotics.’’
  4. “Today, resistance has spread to more than 8% of these bacteria. No one knows precisely how many people have KPC infections because cases aren’t routinely reported to the CDC.”
  5. “One of the only drugs that combats these bugs is polymixin, which was all but abandoned years ago because it is so toxic to the kidneys, Fishman says. As a result, he says, prevention is crucial.”
  6. “”When MRSA started to develop 15 years ago, the industry started producing antibiotics now coming onto the market,” he says. “We’re in the same position with KPCs as we were with staph aureus 15 years ago, except that the pharmaceutical industry isn’t rushing to produce new drugs.”’

NDM-1, CDC, Pharma

 

Kumarasamy K., Toleman M. et,al., “Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological and epidemiological study,” The Lancet Infectious Diseases, Vol 10(9),Pg 597-602, doi:10.1016/S1473-3099(10)70143-2, Published August 2010, Last checked September 17, 2010.

  1. “Enterobacteriaceae with NDM-1 carbapenemases are highly resistant to many antibiotic classes and potentially herald the end of treatment with β-lactams, fluoroquinolones, and aminoglycosides-the main antibiotic classes for the treatment of Gram-negative infections.”
  2. “Most isolate remained susceptible to colistin and tigecyline.”
  3. “Nevertheless, NDM-1-positive K ”pneumoniae” isolates from Haryana were clonal, suggesting that some strains could potentially cause outbreaks. Most ”bla”NDM-1 positive plasmids were readily transferable and prone to rearrangement, losing or (more rarely) gaining DNA on transfer.”
  4. “This transmissibility and plasticity implies an alarming potential to spread and diversify among bacterial populations.”
  5. “This scenario is of great concern because there are few anti-Gram negative antibiotics in the pharmaceutical pipeline and none that are active against NDM-1 producers. Even more disturbing is that most of the Indian isolates from Chennai and Haryana were from community-acquired infections, suggesting that ”bla”NDM-1 is widespread in the environment.”
  6. “Several of the UK source patients had undergone elective, including cosmetic, surgery while visiting India pr Pakistan. India also provides cosmetic surgery for other Europeans and Americans, and ”bla”NDM-1 will likely spread worldwide.”
  7. “The potential for wider international spread of producers and for NDM-1 encoding plasmids to become endemic worldwide, are clear and frightening.”

NDM-1, Public Health

 

Roberts M., “Seagulls ‘may be spreading superbugsBBC News, September 24 2010 http://www.bbc.co.uk/news/health-11374536

  1. “And the scientists believe wild migratory birds may be spreading antibiotic resistance from place to place, and to other animals and humans through their droppings.”
  2. “Migrating birds that fly and travel long distances can act as transporters, or as reservoirs, of antibiotic-resistant bacteria and may consequently have a significant epidemiological role in the dissemination of resistance.”
  3. “The concern is that they could pass on their resistance to bacteria that can evade other antibiotics, ultimately leading to infections that would be incredibly difficult to treat.”
  4. “An expert from the UK’s Health Protection Agency said: “The study suggests that the wider environment has become contaminated with resistant bacteria, which is of concern as these bacteria may get recycled into the food chain. However there is no evidence that the seagulls were carrying the strain of resistant enterococci bacteria seen in hospital patients, which are also found in countries outside the distribution of this gull species.”

NDM-1

 

EditorsNew detector tests for illegal drugs, superbugs in minutesHomeland Security Newswire, October 2 2010 http://homelandsecuritynewswire.com/new-detector-tests-illegal-drugs-superbugs-minutes.

  1. “A new method of detecting illegal drugs and super bugs will be used in a government-backed handheld device that analyses saliva. The Vantix portable reader will be able to test for chemical substances or bacteria such as MRSA in human or animal saliva within minutes”
  2. “Things like feces, urine and saliva are dreadful samples to work with; even in ground up animal feed where we’re detecting illegal use of antibiotics.”

NDM-1, Public Health

 

Sternberg Steve, “Drug-resistant ‘superbugs’ hit 35 states, spread worldwideUSA Today Published September 17, 2010, Last accessed October 27, 2010 http://www.usatoday.com/yourlife/health/medical/2010-09-17-1Asuperbug17_ST_N.htm

  1. “Bacteria that are able to survive every modern antibiotic are cropping up in many U.S. hospitals and are spreading outside the USA, public health officials say.”
  2. “The bugs, reported by hospitals in more than 35 states, typically strike the critically ill and are fatal in 30% to 60% of cases. Israeli doctors are battling an outbreak in Tel Aviv that has been traced to a patient from northern New Jersey, says Neil Fishman, director of infection control and epidemiology at the University of Pennsylvania and president of the Society of Healthcare Epidemiologists.”
  3. “The bacteria are equipped with a gene that enables them to produce an enzyme that disables antibiotics. The enzyme is called Klebsiella pneumoniae carbapenamase, or KPC. It disables carbapenam antibiotics, last-ditch treatments for infections that don’t respond to other drugs.”
  4. “Carbapenam-resistant germs are diagnosed mostly in hospital patients and are not spreading in the community. They’re far more common nationwide than bacteria carrying a gene called NDM-1 that made headlines this week, Fishman says.”
  5. “Although KPCs are most common in New York and New Jersey, Srinivasan says, “they’ve now been reported in more than half of the states.” A decade ago, only 1% of Klebsiella pneumoniae bacteria reported to CDC by hospitals were carbapenam-resistant. Today, resistance has spread to more than 8% of these bacteria. No one knows precisely how many people have KPC infections because cases aren’t routinely reported to the CDC.”
  6. “One of the only drugs that combats these bugs is polymixin, which was all but abandoned years ago because it is so toxic to the kidneys, Fishman says. As a result, he says, prevention is crucial.”
  7. “In March 2009, the CDC gave hospitals new guidelines for prevention. Among other things, doctors treating any patient diagnosed with carbapenam-resistant infections are advised to wear gowns and gloves to protect themselves and make sure they don’t infect other patients.”

KPC, NDM-1, Public Health

 

 

 

 

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