[ Its exact geographical origin, however, has not been conclusively verified. In March 2010, a study in a hospital in ]Mumbai
Mumbai (, ; also known as Bombay — the official name until 1995) is the capital city of the Indian state of Maharashtra and the ''de facto'' financial centre of India. According to the United Nations, as of 2018, Mumbai is the second- ...
found that most carbapenem-resistant bacteria isolated from patients carried the ''blaNDM-1'' gene. Later, the journal editor apologized for allowing the name.
NDM-1 β-lactamase was also found in an ''K. pneumoniae'' isolate from Croatia
, image_flag = Flag of Croatia.svg
, image_coat = Coat of arms of Croatia.svg
, anthem = "Lijepa naša domovino"("Our Beautiful Homeland")
, image_map =
, map_caption =
, capit ...
, and the patient arrived from Bosnia and Herzegovina
Bosnia and Herzegovina ( sh, / , ), abbreviated BiH () or B&H, sometimes called Bosnia–Herzegovina and often known informally as Bosnia, is a country at the crossroads of south and southeast Europe, located in the Balkans. Bosnia and H ...
. The second geographical origin is considered to be eastern Balkans
The Balkans ( ), also known as the Balkan Peninsula, is a geographical area in southeastern Europe with various geographical and historical definitions. The region takes its name from the Balkan Mountains that stretch throughout the who ...
.
In May 2010, a case of infection with ''E. coli'' expressing NDM-1 was reported in Coventry
Coventry ( or ) is a City status in the United Kingdom, city in the West Midlands (county), West Midlands, England. It is on the River Sherbourne. Coventry has been a large settlement for centuries, although it was not founded and given its ...
in the United Kingdom. The patient was a man of Indian origin who had visited India 18 months previously, where he had undergone dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
. In initial assays the bacterium was fully resistant to all antibiotics tested, while later tests found that it was susceptible to tigecycline
Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resist ...
and colistin
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as ''Pseudomonas aeruginosa'', ''Klebsiella ...
. The authors warned that international travel and patients' use of multiple countries' healthcare systems could lead to the "rapid spread of NDM-1 with potentially serious consequences".
, there were three reported cases of Enterobacteriaceae
Enterobacteriaceae is a large family (biology), family of Gram-negative bacteria. It was first proposed by Rahn in 1936, and now includes over 30 genera and more than 100 species. Its classification above the level of family is still a subject ...
isolates bearing this newly described resistance mechanism in the US, the Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) stated that "All three U.S. isolates were from patients having received recent medical care in India." However, US experts stated that it is unclear as to whether this strain is any more dangerous than existing antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus
Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
, which are already common in the USA.
In July 2010, a team in New Delhi reported a cluster of three cases of ''Acinetobacter baumannii
''Acinetobacter baumannii'' is a typically short, almost round, rod-shaped ( coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromi ...
'' bearing ''blaNDM-1'' that were found in the intensive care unit of a hospital in Chennai
Chennai (, ), formerly known as Madras ( the official name until 1996), is the capital city of Tamil Nadu, the southernmost Indian state. The largest city of the state in area and population, Chennai is located on the Coromandel Coast of th ...
, India, in April 2010. As previously, the bacteria were fully resistant to all the aminoglycoside, β-lactam, and quinolone antibiotics, but were susceptible to tigecycline and colistin. This particularly broad spectrum of antibiotic resistance was heightened by the strain's expressing several different resistance genes in addition to ''blaNDM-1''.
A study by a multi-national team was published in the August 2010 issue of the journal ''The Lancet Infectious Diseases
''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823.
The journal publishes original research articles, r ...
''. This examined the emergence and spread of bacteria carrying the ''blaNDM-1'' gene. This reported on 37 cases in the United Kingdom, 44 isolates with NDM-1in Chennai
Chennai (, ), formerly known as Madras ( the official name until 1996), is the capital city of Tamil Nadu, the southernmost Indian state. The largest city of the state in area and population, Chennai is located on the Coromandel Coast of th ...
, 26 in Haryana
Haryana (; ) is an Indian state located in the northern part of the country. It was carved out of the former state of East Punjab on 1 Nov 1966 on a linguistic basis. It is ranked 21st in terms of area, with less than 1.4% () of India's land ar ...
, and 73 in various other sites in Pakistan
Pakistan ( ur, ), officially the Islamic Republic of Pakistan ( ur, , label=none), is a country in South Asia. It is the world's List of countries and dependencies by population, fifth-most populous country, with a population of almost 24 ...
and India. The authors' analysis of the strains showed that many carried ''blaNDM-1'' on plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s, which will allow the gene to be readily transferred between different strains of bacteria by horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...
. All the isolates were resistant to multiple different classes of antibiotics, including beta-lactam antibiotic
β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical
structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and ...
s, fluoroquinolones
A quinolone antibiotic is a member of a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ...
, and aminoglycoside
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
s, but most were still susceptible to the polymyxin
Polymyxins are antibiotics. Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules ...
antibiotic colistin
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as ''Pseudomonas aeruginosa'', ''Klebsiella ...
.
On 21 August 2010, Ontario
Ontario ( ; ) is one of the thirteen provinces and territories of Canada.Ontario is located in the geographic eastern half of Canada, but it has historically and politically been considered to be part of Central Canada. Located in Central Ca ...
, Canada, had its first confirmed case of the "superbug" in Brampton. There were other confirmed cases in British Columbia
British Columbia (commonly abbreviated as BC) is the westernmost province of Canada, situated between the Pacific Ocean and the Rocky Mountains. It has a diverse geography, with rugged landscapes that include rocky coastlines, sandy beaches, ...
and Alberta
Alberta ( ) is one of the thirteen provinces and territories of Canada. It is part of Western Canada and is one of the three prairie provinces. Alberta is bordered by British Columbia to the west, Saskatchewan to the east, the Northwest Ter ...
. These confirmed NDM-1 infected cases have no relationship with New Delhi, India. The patients or their relatives never travelled to India in the last decade.
On 6 September 2010, Japan detected its first ever case of the NDM-1 enzyme. In May 2009, a Japanese man in his 50s who had recently returned from vacation in India was struck with a fever and hospitalized, later making a full recovery. Hospital officials confirmed that tests carried out after the patient's recovery were positive for the NDM-1 enzyme.
An environmental point prevalence study conducted between 26 September and 10 October 2010 found bacteria with the NDM-1 gene in drinking water and seepage samples in New Delhi. 50 tap water samples and 171 seepage samples were collected from sites within 12 km of central New Delhi. Of these samples, 20 strains of bacteria were found to contain NDM-1 gene in 51 out of 171 seepage samples and 2 out of 50 tap water samples.
On 8 May 2012, the presence of NDM was found in a patient who died at Royal Alexandra Hospital in Edmonton, Alberta. The patient was also found to be carrying an ''Acinetobacter
''Acinetobacter'' is a genus of gram-negative bacteria belonging to the wider class of Gammaproteobacteria. ''Acinetobacter'' species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.
They are important ...
'' strain. The patient contracted the bacteria after another patient, who had surgery on the Indian subcontinent, traveled to Canada and was admitted to hospital with an infection.
''Science Daily
''Science Daily'' is an American website launched in 1995 that aggregates press releases and publishes lightly edited press releases (a practice called churnalism) about science, similar to Phys.org and EurekAlert!.
The site was founded by mar ...
'' reported on the 16 December 2013 that a team of scientists from Rice
Rice is the seed of the grass species ''Oryza sativa'' (Asian rice) or less commonly ''Oryza glaberrima
''Oryza glaberrima'', commonly known as African rice, is one of the two domesticated rice species. It was first domesticated and grown i ...
, Nankai and Tianjin
Tianjin (; ; Mandarin: ), alternately romanized as Tientsin (), is a municipality and a coastal metropolis in Northern China on the shore of the Bohai Sea. It is one of the nine national central cities in Mainland China, with a total popul ...
universities found NDM-1 in two wastewater treatment plants in northern China. In fact, the NDM-1 was unable to be removed after several treatments and attempts to disinfect the plants. Disinfection by chlorine, one of the most effective methods currently, also failed to eradicate the beta-lactamase.
In June 2014 it was reported that the molecule aspergillomarasmine A
Aspergillomarasmine A is an polyamino acid naturally produced by the mold ''Aspergillus versicolor''. The substance has been reported to inhibit two antibiotic resistance carbapenemase proteins in bacteria, New Delhi metallo-beta-lactamase 1 (NDM-1 ...
from the Aspergillus
' () is a genus consisting of several hundred mold species found in various climates worldwide.
''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Miche ...
fungus turns off the resistance mechanism of NDM-1 and thus makes bacteria once again sensitive to traditional antibiotics. It has been shown to be effective in mice and rats but has not yet been tested in humans for safety or effectiveness.
In September 2016, a 70-year-old woman in Reno, Nevada, died of septic shock
Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Con ...
following infection with NDM-producing ''Klebsiella pneumoniae
''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
Although found in the normal flora of the mouth ...
''. She had been on an extended trip to India and was admitted to a hospital there for an infected right hip.
Phenotypic detection of NDM-1
Detection of NDM-1 gene depends upon the phenotypic determination of the enzyme activity. These enzymes are zinc dependent and therefore termed as metallo-beta-lactamase. Indian studies have been done which demonstrate their dependency on zinc and the ability of zinc chelating agents like EDTA
Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes eve ...
to decrease their activity. The Modified Hodge Test and the Re-Modified Hodge Test were developed for phenotypical detection on a routine basis in resource limited laboratories.[ Other tests for phenotypic detection are:
* Double disk synergy testing (DDST)
* Vitek detection (Automated system)
* E-test (E-Strip)]
Criticism of enzyme name
The Indian health ministry has disputed the conclusion of the August 2010 ''Lancet'' study that the gene originated in India, describing this conclusion as "unfair" and stating that Indian hospitals are perfectly safe for treatment. Indian politicians have described linking this new drug resistance gene to India as "malicious propaganda" and blamed multinational corporation
A multinational company (MNC), also referred to as a multinational enterprise (MNE), a transnational enterprise (TNE), a transnational corporation (TNC), an international corporation or a stateless corporation with subtle but contrasting senses, i ...
s for what they describe as selective malignancy. A Bharatiya Janata Party
The Bharatiya Janata Party (BJP; ; ) is a political party in India, and one of the two major Indian political parties alongside the Indian National Congress. Since 2014, it has been the ruling political party in India under Narendra Modi ...
politician has instead argued that the journal article is bogus and represented an attempt to scare medical tourists away from India. The Indian Ministry of Health released a statement "strongly refut ng naming the enzyme "New Delhi". A co-author of the 2010 ''Lancet'' study, who is based in the University of Madras
The University of Madras (informally known as Madras University) is a public university, public State university (India), state university in Chennai, Tamil Nadu, India. Established in 1857, it is one of the oldest and among the most prestigiou ...
, has stated that he does not agree with the part of the article that advises people to avoid elective surgeries in India.
In contrast, an editorial in the March 2010 issue of the ''Journal of Association of Physicians of India'' blamed the emergence of this gene on the widespread misuse of antibiotics in the Indian healthcare system, stating that Indian doctors have "not yet taken the issue of antibiotic resistance seriously" and noting little control over the prescription of antibiotics by doctors and even pharmacists. The ''Times of India'' states that there is general agreement among experts that India needs both an improved policy to control the use of antibiotics and a central registry of antibiotic-resistant infections.[
The British journal '']The Lancet
''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823.
The journal publishes original research articles, ...
'' refused to publish a rebuttal from the Indian National Centre for Disease Control, claiming lack of space and that the journal's editors felt it would be better placed elsewhere.
However, on 12January 2011, the editor of ''The Lancet'', Richard Horton, apologized and acknowledged that naming the resistance enzyme after New Delhi
New Delhi (, , ''Naī Dillī'') is the capital of India and a part of the National Capital Territory of Delhi (NCT). New Delhi is the seat of all three branches of the government of India, hosting the Rashtrapati Bhavan, Parliament House ...
was an "error".[ Following this, Ajai R. Singh, editor of ]Mens Sana Monographs
The ''Mens Sana Monographs'' is a peer-reviewed open-access monographic series of mental and physical medicine. It is published by Medknow Publications on behalf of the Mens Sana Research Foundation. Every volume is also published as a book, wit ...
, demanded that such 'geographic names giving' be abandoned and replaced by 'scientific name giving'. He proposed changing NDM-1 to PCM (plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
-encoding carbapenem-resistant metallo-beta-lactamase).
Deaths
The first reported death due to bacteria expressing the NDM-1 enzyme was recorded in August 2010, when a Belgian
Belgian may refer to:
* Something of, or related to, Belgium
* Belgians, people from Belgium or of Belgian descent
* Languages of Belgium, languages spoken in Belgium, such as Dutch, French, and German
*Ancient Belgian language, an extinct languag ...
man infected while undergoing treatment in a hospital in Pakistan
Pakistan ( ur, ), officially the Islamic Republic of Pakistan ( ur, , label=none), is a country in South Asia. It is the world's List of countries and dependencies by population, fifth-most populous country, with a population of almost 24 ...
died despite being administered colistin
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as ''Pseudomonas aeruginosa'', ''Klebsiella ...
. A doctor involved in his treatment said: "He was involved in a car accident during a trip to Pakistan. He was hospitalised with a major leg injury and then repatriated to Belgium, but he was already infected".
In another case, an Indian citizen, died in a hospital because of similar infection.
See also
*Antibiotic resistance
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
* List of antibiotic resistant bacteria
A list of antibiotic resistant bacteria is provided below. These bacteria have shown antibiotic resistance (or antimicrobial resistance).
Enzyme NDM-1 (New Delhi Metallo-beta-lactamase-1)
New Delhi metallo-beta-lactamase 1, NDM-1 is an enzym ...
*Medical tourism
Medical tourism refers to people traveling abroad to obtain medical treatment. In the past, this usually referred to those who traveled from less-developed countries to major medical centers in highly developed countries for treatment unavailable a ...
* Methicillin-resistant ''Staphylococcus aureus''
* MCR-1
*Nosocomial infection
A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is ...
*Transduction (genetics)
Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. An example is the viral transfer of DNA from one bacterium to another and hence an example of horizontal gene transfer. Transduction does no ...
References
External links
BBC News Health - Questions&Answers about NDM-1 superbugs
National Resistance Alert 3 addendum in UK (PDF)
*
*
*
PBS Frontline Oct 22, 2013 Hunting the Nightmare Bacteria
{{DEFAULTSORT:New Delhi Metallo-Beta-Lactamase
Bacterial enzymes
Bacteriology
Beta-lactam antibiotics
EC 3.5.2
Antimicrobial resistance
de:Β-Lactamasen#Carbapenemasen