论文部分内容阅读
【摘要】
【关键词】
【中图分类号】R378【文献标识码】A【文章编号】1001-4128(2011)01-0192-04
NDM-1 in detail:
NDM-1, which is the abbreviation of ‘New Delhi metallo-beta-lactamase’, is a recently discovered enzyme that is produced by some gram-negative Enterobacteriaceae such as E coil (Escherichia coli) and Klebsiella pneumonia. It is named after ‘New Delhi’, which is the capital of India, because the first patient who was diagnosed to be colonized by bacteria with blaNDM-1 gene had gone to a hospital in New Delhi for cosmetic surgery not long before he was diagnosed.
Bacteria with this enzyme-producing gene (designated blaNDM-1), is resistant against all types of beta-lactam antibiotics. Beta-lactam antibiotics are very commonly used and are the main weapon against bacterial infection. They have a special structure known as the beta-lactam ring, and beta-lactamases have the ability to hydrolyze that ring, hence making the effect of the antibiotics obsolete.
Even though this enzyme is not the first beta-lactamase discovered in medical history, it possesses special significance since it is active against newer agents such as carbapenems. Carbapenem antibiotics are the most powerful antibiotics that we recently possess, and are commonly known as ‘the last line of defense’. The downfall of this fortress has shocked the medical field and made specialists aware of the tough challenges that humanity is facing.
According to an article (source 1) on ‘The Lancet Infectious Diseases’, (We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan.) 180 isolates were identified across India, Pakistan and the UK until August 11, 2010, and the infection is slowly spreading across Asia and Europe. Recently, the scale of infection around the world is not high, but it is widely spread amongst UK and southern Asia, as shown in figure 1. Several cases have been found in the US and Hong Kong. Symptoms of NDM-1 infection are no different than common Enterobacteriaceae infection since it is still the same bacteria. Most patients will have fever and fatigue. If bacteria enter the bloodstream, patients may go into shock. It is difficult to tell that the infections are caused by bacteria that express NDM-1 merely by symptoms, other than the observation that patients do not respond to most conventional antibiotics. Bacteria that produce NDM-1 can be identified by carrying out a series of stand test that measure the resistance of bacteria to penicillins, cephalosporins and carbapenems. If the bacteria are resistant to those beta-lactam antibiotics, then the suspicion of NDM-1 is raised. Suspicion is also raised if the patient has sought medical help in India in the past few months.
It is possible to prevent the risk of person-person spread of blaNDM-1 possessing bacteria by practicing good hand and clinical hygiene since intrinsically they are still bacteria. It would be wise to wash or disinfect your hands after using the bathroom and before preparing food. In hospitals and clinics, people should always wear gloves and gowns, and clean their hands regularly.
An article titled ‘Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study’ published on ‘The Lancet Infectious Diseases’ journal is the primary source of this report. ‘The lancet’ is a prestigious medical magazine that publishes articles written by medical professionals and expertise from around the world. This source is very reliable as it is one of the world’s best known, oldest, and most respected general medical journals. Source 4 is also an article from ‘The Lancet’. Source 2: MedicineNet.com is developed by a uniquely experienced team of qualified executives in the fields of medicine, healthcare, internet technology, and business since 1996. Hence it is a reliable source of medical information. Source 3- Medical News today (http://www.medicalnewstoday.com) is a professional website that provides services in the fields of medical news, medical videos, article opinions and medical discussion forums. It is not as prestigious as source 1 and 2, but the information is still reliable. Source 5 is a report written by researchers who work in Microbiology and Tumor Biology Center Karolinska Institute and Swedish Institute for Infectious Disease Control.
Implications of NDM-1-what should we learn from this?
The emerge of the new enzyme NDM-1 has an abstruse meanings and implications towards the ways that we have been using antibiotics since it was first discovered in 1928 by Alexander Fleming. The discovery of penicillin has proclaimed an opening to the antibiotic era and its debut changed our attitude towards bacterial infections. Ever since then antibiotics have saved numerous lives, and have brought benefit to mankind. Table 1 shows some of the most frequently used antibiotics and the mechanisms of their action. As you can see, some of them interfere with cell wall synthesis; some of them inhibit the synthesis of proteins in bacteria etc. Unfortunately, everything has too sides. Bacteria can gain resistance to antibiotics either by horizontal gene transfer, or mutagenesis. The spreading of blaNDM-1 is a typical example of horizontal gene transfer. Under the selection pressure of antibiotics, bacteria evolve into ones with resistant abilities. These bacteria are much harder to treat, and as in source 5 has claimed: ‘mathematical models suggest that the decay time of resistance after a decline in drug use is much longer than the time required for the emergence of antibiotic resistance’. This means that once resistance has arisen in a bacterial population it will persist for long periods of time.
It seems that the emergence of NDM-1 is the price to pay for the overuse and abuse of antibiotics by human. Nature has its ways of defending itself. Sometimes we should suppress our wills of controlling over everything, and let nature has its ways. Scientists and medical researchers have realized this problem a long time ago, but haven’t taken any action. Perhaps the outburst of this enzyme is the wakeup call for human to start searching other solutions to infectious diseases other than frequent antibiotic use.
The wide spread of blaNDM-1 across Asia and Europe also suggested another social problem: Clinical hygiene around the world is not completely under control, and some countries are under the standards. Source 4 suggests that the India government is keen in developing its medical tourism that the clinical hygiene in some hospitals is not very appropriate.
While India government is being misled by the rising revenue, tourists from around the world are not very concerned, or not aware of the consequence of such hospitals. Rather than being in search of reliable clinical institutes, some have been in search of ‘unique mix of cutting-edge technology’, ‘ancient medical traditions’ and ‘cheap costs’ (abstracted and summarized from source 4). Table 2 shows the cost of having procedures in the USA and India. It is not hard to understand why some people prefer India than USA when comes to medical procedures-the cost is lowered by an average of 85% in India. These uncaring lacks of regulations made the NDM-1 carrying bacteria to spread around the world. India is a typical example, but it’s not the only one. It is a nature in man to seek cheap labor and unique techniques, but when it comes to medical procedures, we have to choose our institute wisely.
Risks to humanity:
Because the gene that encodes for NDM-1 has been identified on bacterial plasmids, which are small segments of genetic material, they are easily transferred among bacteria (horizontal gene transfer). In this way, the ability of producing NDM-1 can be passed from one to another, or even from one bacterial genus to another. If NDM-1 jumps on to an already antibiotic resistant bacterium, then the bacterium would very likely to become a superbug (bacteria that are resistant against three or more antibiotics), and it could spread among people very quickly by means as simple as body contact. These infection will be very difficult to treat, or even untreatable in some cases.
The question ‘whether NDM-1 is going to start a worldwide health hazard’ is quite controversial in the medical society. Some say its scale will be similar to that of the H1N1-it will infect and kill some people, but not serious enough to cause health hazards if its spread is controlled properly. Some say it could be like SARS, which spreads around the world or one region very quickly and is extremely deadly. The consequence depends on the type of bacteria that will inherit/acquire the blaNDM-1 gene in the future, and which antibiotics they are resistant to. If the bacteria itself is no harm, then it will not deal much damage to our body even though it has the ability to synthesis NDM-1. However, if we do not control the spread of blaNDM-1, more and more bacteria will have the antibiotic resistant ability. Therefore harmful bacteria will have more chance to obtain the gene. If so, the antibiotic arsenal that has been built up by human throughout the years would be compromised.
The discovery of New Delhi metallo-beta-lactamase created a threat for India’s medical tourism industry. After the article about the research result of NDM-1 has been first published on ‘The Lancet’ magazine, India government refused the naming of the enzyme because it might consequently ruin the country’s reputation in medical industry. But eventually the enzyme was named after the capital of India since the authors of the article insisted on the claim that NDM1 bacteria is originated in India and spread by Indian. Hence India’s Image got damaged continuously by the many specialists, authentic organizations and stories published by many sites, newspapers, magazines, health journals. The suggestion given by the media, which includes avoiding travelling to in India and avoid unnecessary surgeries from India, are diversely affecting India’s image and medical tourism.
The medical tourism industry in India had been growing fast. The Confederation of Indian Industry predicts that India will see revenues of US$2 billion from medical tourism by 2012. Captivated by this economic potential, the Indian Government is actively courting international patients. Yet despite the industry’s predicted growth of 30% in India, the country has not produced any national medical guidelines on this issue. Nowadays, people will think twice before going to India for cosmetic, elastic or other surgeries. As a consequence, India has lost over 60% of its growth in the tourism industry.
Perhaps India deserves the loss, the criticism and the blame, for they do not have strict regulations in the usage of antibiotics across the country. Perhaps that is why NDM-1 has originated from India.
Fighting for a cure:
Recently, there is no treatment or cure for an infection caused by bacteria that make NDM-1 because it is pretty much resistant against all commonly used antibiotics. Some strands of bacteria consisting blaNDM-1 are not resistant against colistin, but colistin is an older antibiotic that has not been used much in recent decades because it is toxic. Besides, such bacteria only exist in a small percentage.
Scientist predicted that a complete cure will be found after 10-20 years of research. It takes a long time to develop a new antibiotic since there has to be a lot of testing and trials. Another reason for why we couldn’t find a cure quickly is that over the past decades, medical researchers have mostly been working on antibiotics that could fight off gram-positive bacteria, since they displayed more threat than gram-negative bacteria in the past few years. They expected the grand barrier of carbapenem antibiotics to last a bit longer. Unfortunately, NDM-1 is mostly found in gram negative bacteria such as E. coli and K pneumoniae.
The good news is that 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, but it does provide us with hope.
Whilst scientists are developing new antibiotics, an alternative ‘cure’ for the NDM-1 is to stop it from spreading from person to person. This is considered a cure because it is something that we can all take part in. As mentioned above, everyone should be fully aware of how the gene can spread and take appropriate precautions such as practicing good hand hygiene and clinical hygiene. Patients infected with bacteria that possess NDM-1 enzyme should be quarantined and carefully monitored until the infection wears off. Prevention is better than cure, since the situation would be better off if there is no bacteria infected with the gene in the first place.
References
[1] Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study (The Lancet Infectious Diseases, Volume 10, Issue 9, Pages 597-602, September 2010)
[2] MedicineNet.com (“NDM-1 (New Delhi metallo-beta-lactamase)”, http://www.medicinenet.com/ndm-1/article.htm, Medical Author: Mary D. Nettleman, MD, MS, MACP; Medical Editor: Charles Davis, MD, PhD;9/17/2010)
[3] Medical News Today (“What is NDM-1?”, Article Date: 12 Aug 2010 - 8:00 PDT, Written by Christian Nordqvist)
[4] Medical tourism booms in India, but at what cost? (The Lancet, Volume 376, Issue 9742, Pages 671 - 672, 28 August 2010)
[5] Bacterial Adaptation To Novel Selection Pressures (page 22-25, Microbiology and Tumor Biology Center Karolinska Institute and Swedish Institute for Infectious Disease Control, Stockholm Sweden, Annika Nilsson)
【关键词】
【中图分类号】R378【文献标识码】A【文章编号】1001-4128(2011)01-0192-04
NDM-1 in detail:
NDM-1, which is the abbreviation of ‘New Delhi metallo-beta-lactamase’, is a recently discovered enzyme that is produced by some gram-negative Enterobacteriaceae such as E coil (Escherichia coli) and Klebsiella pneumonia. It is named after ‘New Delhi’, which is the capital of India, because the first patient who was diagnosed to be colonized by bacteria with blaNDM-1 gene had gone to a hospital in New Delhi for cosmetic surgery not long before he was diagnosed.
Bacteria with this enzyme-producing gene (designated blaNDM-1), is resistant against all types of beta-lactam antibiotics. Beta-lactam antibiotics are very commonly used and are the main weapon against bacterial infection. They have a special structure known as the beta-lactam ring, and beta-lactamases have the ability to hydrolyze that ring, hence making the effect of the antibiotics obsolete.
Even though this enzyme is not the first beta-lactamase discovered in medical history, it possesses special significance since it is active against newer agents such as carbapenems. Carbapenem antibiotics are the most powerful antibiotics that we recently possess, and are commonly known as ‘the last line of defense’. The downfall of this fortress has shocked the medical field and made specialists aware of the tough challenges that humanity is facing.
According to an article (source 1) on ‘The Lancet Infectious Diseases’, (We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan.) 180 isolates were identified across India, Pakistan and the UK until August 11, 2010, and the infection is slowly spreading across Asia and Europe. Recently, the scale of infection around the world is not high, but it is widely spread amongst UK and southern Asia, as shown in figure 1. Several cases have been found in the US and Hong Kong. Symptoms of NDM-1 infection are no different than common Enterobacteriaceae infection since it is still the same bacteria. Most patients will have fever and fatigue. If bacteria enter the bloodstream, patients may go into shock. It is difficult to tell that the infections are caused by bacteria that express NDM-1 merely by symptoms, other than the observation that patients do not respond to most conventional antibiotics. Bacteria that produce NDM-1 can be identified by carrying out a series of stand test that measure the resistance of bacteria to penicillins, cephalosporins and carbapenems. If the bacteria are resistant to those beta-lactam antibiotics, then the suspicion of NDM-1 is raised. Suspicion is also raised if the patient has sought medical help in India in the past few months.
It is possible to prevent the risk of person-person spread of blaNDM-1 possessing bacteria by practicing good hand and clinical hygiene since intrinsically they are still bacteria. It would be wise to wash or disinfect your hands after using the bathroom and before preparing food. In hospitals and clinics, people should always wear gloves and gowns, and clean their hands regularly.
An article titled ‘Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study’ published on ‘The Lancet Infectious Diseases’ journal is the primary source of this report. ‘The lancet’ is a prestigious medical magazine that publishes articles written by medical professionals and expertise from around the world. This source is very reliable as it is one of the world’s best known, oldest, and most respected general medical journals. Source 4 is also an article from ‘The Lancet’. Source 2: MedicineNet.com is developed by a uniquely experienced team of qualified executives in the fields of medicine, healthcare, internet technology, and business since 1996. Hence it is a reliable source of medical information. Source 3- Medical News today (http://www.medicalnewstoday.com) is a professional website that provides services in the fields of medical news, medical videos, article opinions and medical discussion forums. It is not as prestigious as source 1 and 2, but the information is still reliable. Source 5 is a report written by researchers who work in Microbiology and Tumor Biology Center Karolinska Institute and Swedish Institute for Infectious Disease Control.
Implications of NDM-1-what should we learn from this?
The emerge of the new enzyme NDM-1 has an abstruse meanings and implications towards the ways that we have been using antibiotics since it was first discovered in 1928 by Alexander Fleming. The discovery of penicillin has proclaimed an opening to the antibiotic era and its debut changed our attitude towards bacterial infections. Ever since then antibiotics have saved numerous lives, and have brought benefit to mankind. Table 1 shows some of the most frequently used antibiotics and the mechanisms of their action. As you can see, some of them interfere with cell wall synthesis; some of them inhibit the synthesis of proteins in bacteria etc. Unfortunately, everything has too sides. Bacteria can gain resistance to antibiotics either by horizontal gene transfer, or mutagenesis. The spreading of blaNDM-1 is a typical example of horizontal gene transfer. Under the selection pressure of antibiotics, bacteria evolve into ones with resistant abilities. These bacteria are much harder to treat, and as in source 5 has claimed: ‘mathematical models suggest that the decay time of resistance after a decline in drug use is much longer than the time required for the emergence of antibiotic resistance’. This means that once resistance has arisen in a bacterial population it will persist for long periods of time.
It seems that the emergence of NDM-1 is the price to pay for the overuse and abuse of antibiotics by human. Nature has its ways of defending itself. Sometimes we should suppress our wills of controlling over everything, and let nature has its ways. Scientists and medical researchers have realized this problem a long time ago, but haven’t taken any action. Perhaps the outburst of this enzyme is the wakeup call for human to start searching other solutions to infectious diseases other than frequent antibiotic use.
The wide spread of blaNDM-1 across Asia and Europe also suggested another social problem: Clinical hygiene around the world is not completely under control, and some countries are under the standards. Source 4 suggests that the India government is keen in developing its medical tourism that the clinical hygiene in some hospitals is not very appropriate.
While India government is being misled by the rising revenue, tourists from around the world are not very concerned, or not aware of the consequence of such hospitals. Rather than being in search of reliable clinical institutes, some have been in search of ‘unique mix of cutting-edge technology’, ‘ancient medical traditions’ and ‘cheap costs’ (abstracted and summarized from source 4). Table 2 shows the cost of having procedures in the USA and India. It is not hard to understand why some people prefer India than USA when comes to medical procedures-the cost is lowered by an average of 85% in India. These uncaring lacks of regulations made the NDM-1 carrying bacteria to spread around the world. India is a typical example, but it’s not the only one. It is a nature in man to seek cheap labor and unique techniques, but when it comes to medical procedures, we have to choose our institute wisely.
Risks to humanity:
Because the gene that encodes for NDM-1 has been identified on bacterial plasmids, which are small segments of genetic material, they are easily transferred among bacteria (horizontal gene transfer). In this way, the ability of producing NDM-1 can be passed from one to another, or even from one bacterial genus to another. If NDM-1 jumps on to an already antibiotic resistant bacterium, then the bacterium would very likely to become a superbug (bacteria that are resistant against three or more antibiotics), and it could spread among people very quickly by means as simple as body contact. These infection will be very difficult to treat, or even untreatable in some cases.
The question ‘whether NDM-1 is going to start a worldwide health hazard’ is quite controversial in the medical society. Some say its scale will be similar to that of the H1N1-it will infect and kill some people, but not serious enough to cause health hazards if its spread is controlled properly. Some say it could be like SARS, which spreads around the world or one region very quickly and is extremely deadly. The consequence depends on the type of bacteria that will inherit/acquire the blaNDM-1 gene in the future, and which antibiotics they are resistant to. If the bacteria itself is no harm, then it will not deal much damage to our body even though it has the ability to synthesis NDM-1. However, if we do not control the spread of blaNDM-1, more and more bacteria will have the antibiotic resistant ability. Therefore harmful bacteria will have more chance to obtain the gene. If so, the antibiotic arsenal that has been built up by human throughout the years would be compromised.
The discovery of New Delhi metallo-beta-lactamase created a threat for India’s medical tourism industry. After the article about the research result of NDM-1 has been first published on ‘The Lancet’ magazine, India government refused the naming of the enzyme because it might consequently ruin the country’s reputation in medical industry. But eventually the enzyme was named after the capital of India since the authors of the article insisted on the claim that NDM1 bacteria is originated in India and spread by Indian. Hence India’s Image got damaged continuously by the many specialists, authentic organizations and stories published by many sites, newspapers, magazines, health journals. The suggestion given by the media, which includes avoiding travelling to in India and avoid unnecessary surgeries from India, are diversely affecting India’s image and medical tourism.
The medical tourism industry in India had been growing fast. The Confederation of Indian Industry predicts that India will see revenues of US$2 billion from medical tourism by 2012. Captivated by this economic potential, the Indian Government is actively courting international patients. Yet despite the industry’s predicted growth of 30% in India, the country has not produced any national medical guidelines on this issue. Nowadays, people will think twice before going to India for cosmetic, elastic or other surgeries. As a consequence, India has lost over 60% of its growth in the tourism industry.
Perhaps India deserves the loss, the criticism and the blame, for they do not have strict regulations in the usage of antibiotics across the country. Perhaps that is why NDM-1 has originated from India.
Fighting for a cure:
Recently, there is no treatment or cure for an infection caused by bacteria that make NDM-1 because it is pretty much resistant against all commonly used antibiotics. Some strands of bacteria consisting blaNDM-1 are not resistant against colistin, but colistin is an older antibiotic that has not been used much in recent decades because it is toxic. Besides, such bacteria only exist in a small percentage.
Scientist predicted that a complete cure will be found after 10-20 years of research. It takes a long time to develop a new antibiotic since there has to be a lot of testing and trials. Another reason for why we couldn’t find a cure quickly is that over the past decades, medical researchers have mostly been working on antibiotics that could fight off gram-positive bacteria, since they displayed more threat than gram-negative bacteria in the past few years. They expected the grand barrier of carbapenem antibiotics to last a bit longer. Unfortunately, NDM-1 is mostly found in gram negative bacteria such as E. coli and K pneumoniae.
The good news is that 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, but it does provide us with hope.
Whilst scientists are developing new antibiotics, an alternative ‘cure’ for the NDM-1 is to stop it from spreading from person to person. This is considered a cure because it is something that we can all take part in. As mentioned above, everyone should be fully aware of how the gene can spread and take appropriate precautions such as practicing good hand hygiene and clinical hygiene. Patients infected with bacteria that possess NDM-1 enzyme should be quarantined and carefully monitored until the infection wears off. Prevention is better than cure, since the situation would be better off if there is no bacteria infected with the gene in the first place.
References
[1] Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study (The Lancet Infectious Diseases, Volume 10, Issue 9, Pages 597-602, September 2010)
[2] MedicineNet.com (“NDM-1 (New Delhi metallo-beta-lactamase)”, http://www.medicinenet.com/ndm-1/article.htm, Medical Author: Mary D. Nettleman, MD, MS, MACP; Medical Editor: Charles Davis, MD, PhD;9/17/2010)
[3] Medical News Today (“What is NDM-1?”, Article Date: 12 Aug 2010 - 8:00 PDT, Written by Christian Nordqvist)
[4] Medical tourism booms in India, but at what cost? (The Lancet, Volume 376, Issue 9742, Pages 671 - 672, 28 August 2010)
[5] Bacterial Adaptation To Novel Selection Pressures (page 22-25, Microbiology and Tumor Biology Center Karolinska Institute and Swedish Institute for Infectious Disease Control, Stockholm Sweden, Annika Nilsson)