medscape 討論NDM-1
http://www.medscape.com/viewarticle/728118_3
carbapenem resistant enterobacteriae 已經在美國很多了，要通報
但是NDM-1之所以引人注意是因為他和之前的carbapenemase不同來源
而且他可以在許多種plasmids上傳來傳去，傳得快
預計會造成Healthcare associated infection, 也可以造成community infection
From Medscape Internal Medicine
NDM-1 -- Making Resistant Bugs in New Ways
Carol Peckham
Posted: 09/13/2010
Introduction
A report in Lancet Infectious Disease has described the New Delhi metallo-beta-lactamase 1 (NDM-1), a unique genetic mechanism identified in India, Pakistan, and the United Kingdom that has produced antibiotic-resistant gram-negative Enterobacteriaceae. [1] The strain was identified by the Centers for Disease Control and Prevention (CDC) in 3 isolates in the United States. To determine what threat this might pose, Medscape interviewed Alex Kallen, MD, and Brandi M. Limbago, PhD, both in the Division of Healthcare Quality Promotion, who provided perspective from Centers for Disease Control and Prevention (CDC). Alex Kallen, MD, is a Medical Officer and Brandi M. Limbago, PhD, is Lead of the Antimicrobial Resistance and Characterization Laboratory at the CDC.
The Interview
Medscape: Since the publication of the article in Lancet Infectious Disease on antibiotic-resistant gram-negative Enterobacteriaceae conferred by the New Delhi metallo-beta-lactamase 1 (NDM-1),[1] there are now great concerns about an infectious disease pandemic produced by this strain. According to Professor Tim Walsh of Cardiff University, who discovered the gene, as quoted in the UK Guardian,[2] in just 3 years it has grown in prevalence from being rarely observed at all to existing in between 1% and 3% in patients with Enterobacteriaceae infections in India. Where else has this strain been identified and how seriously is the CDC currently taking this threat?
Brandi Limbago, MD: We have identified this strain in clinical isolates from 3 different US states -- California, Illinois, and Massachusetts. We're taking this threat seriously because this is the first time that we have detected the presence of metallo-beta-lactamase genes in Enterobacteriaceae at all in the United States. The mechanisms of metallo-beta-lactamases have been described sporadically in the literature and in other countries, but we've never seen them in the United States before this.
Alex Kallen, MD: If I could just add one thing, I think what Brandi said is exactly correct, but we should also keep in mind that although the NDM-1 mechanism is new in the United States, carbapenem resistance in Enterobacteriaceae is not. In fact, we have a huge problem with carbapenem resistance from Klebsiella pneumoniae carbapenemases (KPC), which is endemic in some areas of the United States. So that adds to the concern that we have at CDC -- not just for the NDM-1 isolates, but also for all the carbapenem-resistant isolates. These are highly resistant bugs that we want to target. Our approach right now has been to target the resistant phenotype -- not the particular mechanism.
Medscape: How does the NDM-1 gene work in increasing the number of drug-resistant bacteria? Do other carbapenem isolates work in a similar way?
Dr. Limbago: No, the NDM-1 gene is a unique mechanism for resistance. It does not appear to be closely related to either other metallo-beta-lactamases or other carbapenemases. Defining different kinds of enzymes is long and involved, but basically one way is to look at the gene's DNA and protein sequences and then compare them to other known resistance mechanism genes. This one is not closely related to anything that has been described before. The NDM-1 gene specifically is a novel mechanism. The interesting feature is the way that it's increasing drug resistance in the Enterobacteriaceae. It appears to be contained on and able to exist on multiple different kinds of plasmids, sometimes even in the same bacterial cell. So it has multiple ways of moving. For a lot of bacteria we see only clonal expansion, or direct transmission of 1 bacterial strain. With the NDM-1-containing strains, there can be both clonal expansion, which has been documented, and plasmid transmissions, which were described in the Lancet Infectious Diseases report. It also looks as though there are other mechanisms that move this gene around. So there are many differences in the types -- in the bacterial strains carrying the NDM-1 mechanism, in the plasmids that are carrying the gene, and additional variations when researchers artificially move the plasmid from one strain to another. They actually see the gene or the plasmids changing in that process as well, so it appears to be very mutable.
Medscape: It seems surprising that more instances of NDM-1 haven't been identified.
Dr. Limbago: India, where we think this originated, doesn't appear to have very good surveillance mechanisms in place. They don't have much historic data or tracking. It was the emergence of NDM-1 in the United Kingdom that probably got it on the map.
Medscape: What infections caused by the bacteria are most likely to show up, and would you anticipate that they would become as serious as methcillin-resistant Staphylococcus aureus (MRSA)?
Dr. Limbago: It's hard to speculate, but, as with carbapenem-resistant strains seen historically, I think we can say that they will be healthcare-associated infections. Although, judging by the Lancet Infectious Diseases article, we might see community infections as well. Those that we've seen caused by Enterobacteriaceae in the United States tend to be urinary tract infections, but they also can cause other healthcare-associated infections, such as ventilator-associated pneumonias. We would anticipate to see this first in the United States among urinary tract infections and then mainly among people who have exposure in healthcare settings.
Medscape: Would there be any difference in clinical manifestations of urinary tract infections caused by these bacteria as opposed to the other bacteria?
Dr. Limbago: There is no evidence for that.
Dr. Kallen: I don't think we would expect that to be the case.
Dr. Limbago: Right. These are not virulence determinants. They are just harder to treat.
Medscape: Most antibiotic classes are ineffective against this strain. Are there any that can be used to treat it?
Dr. Kallen: Again, we don't have very great experience with treating infections caused by NDM-1, only having 3 in the United States. I think as far as susceptibility is concerned, at least among the isolates that we've tested, that antimicrobials such as the polymyxins and tigercyclines would be effective, and, possibly, aztreonam.
Dr. Limbago: This particular metallo-beta-lactamase -- this particular class of enzymes -- renders all of the beta-lactam agents ineffective, which includes penicillin and all the cephalosporins. Aztreonam is related and identified with that class, but this particular gene doesn't confer resistance to aztreonam. However, all 3 of the clinical isolates that we've seen, as well as the original Swedish isolate described in 2009, are resistant to aztreonam, presumably by other mechanisms.
Dr. Kallen: This is important, because obviously these resistance mechanisms often travel together.
Dr. Limbago: Right. That's another important distinction. This particular NDM mechanism, like other carbapenemase mechanisms, affects the carbapenems, the cephalosporins -- all of the beta-lactam class of drugs, but the bacteria affected by this mechanism are also carrying around other ways of being resistant to multiple agents.
Medscape: Is there any other strain that's actually resistant to all antibiotics?
Dr. Limbago: We've definitely seen, sporadically, isolates that can be resistant to all antibiotics.
Dr. Kallen: Yes, there's an article in Clinical Infectious Diseases that came out in 2009 that described 2 pan-resistant KPCs found in New York City.[3] So, they do appear sporadically already with the KPCs and other forms of carbapenem resistance. We haven't seen it in NDM-1 yet but of course we've only seen 3 isolates.
Medscape: What's the approach when an infection is totally resistant to antibiotics? Is it just supportive?
Dr. Kallen: It varies and depends on the type of infection. Sometimes infections can get better if the source is drained, or, if there's a device involved, it can be removed. However, again, this type of resistance obviously makes infections much more difficult to treat.
Medscape: Is there any indication that medical tourism will be a significant factor in spreading these resistant bacteria, and how would a doctor counsel a patient who wants to go abroad for medical or surgical treatment?
Dr. Kallen: The first thing I want to point out is that of the 3 isolates that we had in the United States so far, none were results of medical tourism, so at least in this country we haven't recognized that as a problem. Certainly, we acknowledge that it's a potential problem, and your readers can get more information from the CDC's Yellow Book, which has a section about medical tourism. One thing to keep in mind of course is that when people go for medical care in the United States, many organizations, including the CDC, the Department of Health and Human Services, and others try to ensure that patient care meets certain standards for quality and safety. When people travel outside the United States for medical care, we no longer have control over these aspects. It is important then for patients to be cognizant of that fact and to do the best they can to obtain good information on levels of quality either from the medical centers where they're going or from the people who are sending them there.
Medscape: What other precautions should be taken to prevent the spread of resistant bacteria? Of course, we know overprescribing antibiotics is a big problem, but are there any other precautions that clinicians can take or patients can take to help reduce the risk either when traveling abroad or here in the United States?
Dr. Kallen: Speaking specifically to the carbapenem-resistant strains, in 2009 the CDC published recommendations for acute care facilities on how to control these isolates.[4] This isn't just for NDM-1; it's for all carbapenem-resistant strains. We need to do a better job promoting those kinds of recommendations, which include making sure that these isolates are recognized. Carbapenem-resistant strains are very common in some parts of the United States, but some places haven't seen many of them yet and still have the potential to intervene and to prevent these strains from becoming endemic.
Dr. Limbago: I want to add that the 2009 MMWR report that Dr. Kallen referred to talks about detection and infection control to prevent the spread of carbapenem-resistant Enterobacteriaceae. There's also a brief MMWR report this year describing the detection of the NDM.[5]
In that second report, we ask that clinicians who identify a patient with carbapenem-resistant Enterobacteriaceae, especially in a nonendemic area, inquire specifically about whether that patient has been to India or Pakistan and whether he or she received medical care there. Then, the clinicians should forward on to their state labs and CDC any isolates associated with travel and medical care in those countries.
Medscape: Thanks so much for taking the time to talk to us.
Summary Points
* The New Delhi metallo-beta-lactamase 1 (NDM-1) is a novel mechanism that has conferred carbapenem resistance on gram-negative Enterobacteriaceae.
* NDM-1 is of particular concern because it appears to have multiple ways of moving and so enabling the spread of resistant pathogens;
* It was first identified in India, Pakistan, and the United Kingdom and recently 3 isolated cases have been found in the United States (in California, Illinois, and Massachusetts).
* Carbapenem resistance in Enterobacteriaceae is not unique to NDM-1. It is a major problem in Klebsiella pneumoniae carbapenemases (KPC), which is endemic in some areas of the United States.
* In the United States, NDM-1 would most likely first be identified in urinary tract infections, mainly among people who have exposure in healthcare settings.
* The 3 NDM-1 clinical isolates currently identified in the United States were not a result of medical tourism. However, patients who travel overseas for medical care should obtain good information on levels of quality either from the medical centers where they're going or from the people who are sending them there. A good source of information on medical tourism can be found in the CDC yellow book.
* Clinicians who identify patients with carbapenem-resistant Enterobacteriaceae, especially in a nonendemic area, should inquire specifically about whether that patient has been abroad to India or Pakistan and whether he or she received medical care there. Then, the clinician should forward on to their state labs and CDC any isolates associated with travel and medical care in those countries.
carbapenem resistant enterobacteriae 已經在美國很多了，要通報
但是NDM-1之所以引人注意是因為他和之前的carbapenemase不同來源
而且他可以在許多種plasmids上傳來傳去，傳得快
預計會造成Healthcare associated infection, 也可以造成community infection
From Medscape Internal Medicine
NDM-1 -- Making Resistant Bugs in New Ways
Carol Peckham
Posted: 09/13/2010
Introduction
A report in Lancet Infectious Disease has described the New Delhi metallo-beta-lactamase 1 (NDM-1), a unique genetic mechanism identified in India, Pakistan, and the United Kingdom that has produced antibiotic-resistant gram-negative Enterobacteriaceae. [1] The strain was identified by the Centers for Disease Control and Prevention (CDC) in 3 isolates in the United States. To determine what threat this might pose, Medscape interviewed Alex Kallen, MD, and Brandi M. Limbago, PhD, both in the Division of Healthcare Quality Promotion, who provided perspective from Centers for Disease Control and Prevention (CDC). Alex Kallen, MD, is a Medical Officer and Brandi M. Limbago, PhD, is Lead of the Antimicrobial Resistance and Characterization Laboratory at the CDC.
The Interview
Medscape: Since the publication of the article in Lancet Infectious Disease on antibiotic-resistant gram-negative Enterobacteriaceae conferred by the New Delhi metallo-beta-lactamase 1 (NDM-1),[1] there are now great concerns about an infectious disease pandemic produced by this strain. According to Professor Tim Walsh of Cardiff University, who discovered the gene, as quoted in the UK Guardian,[2] in just 3 years it has grown in prevalence from being rarely observed at all to existing in between 1% and 3% in patients with Enterobacteriaceae infections in India. Where else has this strain been identified and how seriously is the CDC currently taking this threat?
Brandi Limbago, MD: We have identified this strain in clinical isolates from 3 different US states -- California, Illinois, and Massachusetts. We're taking this threat seriously because this is the first time that we have detected the presence of metallo-beta-lactamase genes in Enterobacteriaceae at all in the United States. The mechanisms of metallo-beta-lactamases have been described sporadically in the literature and in other countries, but we've never seen them in the United States before this.
Alex Kallen, MD: If I could just add one thing, I think what Brandi said is exactly correct, but we should also keep in mind that although the NDM-1 mechanism is new in the United States, carbapenem resistance in Enterobacteriaceae is not. In fact, we have a huge problem with carbapenem resistance from Klebsiella pneumoniae carbapenemases (KPC), which is endemic in some areas of the United States. So that adds to the concern that we have at CDC -- not just for the NDM-1 isolates, but also for all the carbapenem-resistant isolates. These are highly resistant bugs that we want to target. Our approach right now has been to target the resistant phenotype -- not the particular mechanism.
Medscape: How does the NDM-1 gene work in increasing the number of drug-resistant bacteria? Do other carbapenem isolates work in a similar way?
Dr. Limbago: No, the NDM-1 gene is a unique mechanism for resistance. It does not appear to be closely related to either other metallo-beta-lactamases or other carbapenemases. Defining different kinds of enzymes is long and involved, but basically one way is to look at the gene's DNA and protein sequences and then compare them to other known resistance mechanism genes. This one is not closely related to anything that has been described before. The NDM-1 gene specifically is a novel mechanism. The interesting feature is the way that it's increasing drug resistance in the Enterobacteriaceae. It appears to be contained on and able to exist on multiple different kinds of plasmids, sometimes even in the same bacterial cell. So it has multiple ways of moving. For a lot of bacteria we see only clonal expansion, or direct transmission of 1 bacterial strain. With the NDM-1-containing strains, there can be both clonal expansion, which has been documented, and plasmid transmissions, which were described in the Lancet Infectious Diseases report. It also looks as though there are other mechanisms that move this gene around. So there are many differences in the types -- in the bacterial strains carrying the NDM-1 mechanism, in the plasmids that are carrying the gene, and additional variations when researchers artificially move the plasmid from one strain to another. They actually see the gene or the plasmids changing in that process as well, so it appears to be very mutable.
Medscape: It seems surprising that more instances of NDM-1 haven't been identified.
Dr. Limbago: India, where we think this originated, doesn't appear to have very good surveillance mechanisms in place. They don't have much historic data or tracking. It was the emergence of NDM-1 in the United Kingdom that probably got it on the map.
Medscape: What infections caused by the bacteria are most likely to show up, and would you anticipate that they would become as serious as methcillin-resistant Staphylococcus aureus (MRSA)?
Dr. Limbago: It's hard to speculate, but, as with carbapenem-resistant strains seen historically, I think we can say that they will be healthcare-associated infections. Although, judging by the Lancet Infectious Diseases article, we might see community infections as well. Those that we've seen caused by Enterobacteriaceae in the United States tend to be urinary tract infections, but they also can cause other healthcare-associated infections, such as ventilator-associated pneumonias. We would anticipate to see this first in the United States among urinary tract infections and then mainly among people who have exposure in healthcare settings.
Medscape: Would there be any difference in clinical manifestations of urinary tract infections caused by these bacteria as opposed to the other bacteria?
Dr. Limbago: There is no evidence for that.
Dr. Kallen: I don't think we would expect that to be the case.
Dr. Limbago: Right. These are not virulence determinants. They are just harder to treat.
Medscape: Most antibiotic classes are ineffective against this strain. Are there any that can be used to treat it?
Dr. Kallen: Again, we don't have very great experience with treating infections caused by NDM-1, only having 3 in the United States. I think as far as susceptibility is concerned, at least among the isolates that we've tested, that antimicrobials such as the polymyxins and tigercyclines would be effective, and, possibly, aztreonam.
Dr. Limbago: This particular metallo-beta-lactamase -- this particular class of enzymes -- renders all of the beta-lactam agents ineffective, which includes penicillin and all the cephalosporins. Aztreonam is related and identified with that class, but this particular gene doesn't confer resistance to aztreonam. However, all 3 of the clinical isolates that we've seen, as well as the original Swedish isolate described in 2009, are resistant to aztreonam, presumably by other mechanisms.
Dr. Kallen: This is important, because obviously these resistance mechanisms often travel together.
Dr. Limbago: Right. That's another important distinction. This particular NDM mechanism, like other carbapenemase mechanisms, affects the carbapenems, the cephalosporins -- all of the beta-lactam class of drugs, but the bacteria affected by this mechanism are also carrying around other ways of being resistant to multiple agents.
Medscape: Is there any other strain that's actually resistant to all antibiotics?
Dr. Limbago: We've definitely seen, sporadically, isolates that can be resistant to all antibiotics.
Dr. Kallen: Yes, there's an article in Clinical Infectious Diseases that came out in 2009 that described 2 pan-resistant KPCs found in New York City.[3] So, they do appear sporadically already with the KPCs and other forms of carbapenem resistance. We haven't seen it in NDM-1 yet but of course we've only seen 3 isolates.
Medscape: What's the approach when an infection is totally resistant to antibiotics? Is it just supportive?
Dr. Kallen: It varies and depends on the type of infection. Sometimes infections can get better if the source is drained, or, if there's a device involved, it can be removed. However, again, this type of resistance obviously makes infections much more difficult to treat.
Medscape: Is there any indication that medical tourism will be a significant factor in spreading these resistant bacteria, and how would a doctor counsel a patient who wants to go abroad for medical or surgical treatment?
Dr. Kallen: The first thing I want to point out is that of the 3 isolates that we had in the United States so far, none were results of medical tourism, so at least in this country we haven't recognized that as a problem. Certainly, we acknowledge that it's a potential problem, and your readers can get more information from the CDC's Yellow Book, which has a section about medical tourism. One thing to keep in mind of course is that when people go for medical care in the United States, many organizations, including the CDC, the Department of Health and Human Services, and others try to ensure that patient care meets certain standards for quality and safety. When people travel outside the United States for medical care, we no longer have control over these aspects. It is important then for patients to be cognizant of that fact and to do the best they can to obtain good information on levels of quality either from the medical centers where they're going or from the people who are sending them there.
Medscape: What other precautions should be taken to prevent the spread of resistant bacteria? Of course, we know overprescribing antibiotics is a big problem, but are there any other precautions that clinicians can take or patients can take to help reduce the risk either when traveling abroad or here in the United States?
Dr. Kallen: Speaking specifically to the carbapenem-resistant strains, in 2009 the CDC published recommendations for acute care facilities on how to control these isolates.[4] This isn't just for NDM-1; it's for all carbapenem-resistant strains. We need to do a better job promoting those kinds of recommendations, which include making sure that these isolates are recognized. Carbapenem-resistant strains are very common in some parts of the United States, but some places haven't seen many of them yet and still have the potential to intervene and to prevent these strains from becoming endemic.
Dr. Limbago: I want to add that the 2009 MMWR report that Dr. Kallen referred to talks about detection and infection control to prevent the spread of carbapenem-resistant Enterobacteriaceae. There's also a brief MMWR report this year describing the detection of the NDM.[5]
In that second report, we ask that clinicians who identify a patient with carbapenem-resistant Enterobacteriaceae, especially in a nonendemic area, inquire specifically about whether that patient has been to India or Pakistan and whether he or she received medical care there. Then, the clinicians should forward on to their state labs and CDC any isolates associated with travel and medical care in those countries.
Medscape: Thanks so much for taking the time to talk to us.
Summary Points
* The New Delhi metallo-beta-lactamase 1 (NDM-1) is a novel mechanism that has conferred carbapenem resistance on gram-negative Enterobacteriaceae.
* NDM-1 is of particular concern because it appears to have multiple ways of moving and so enabling the spread of resistant pathogens;
* It was first identified in India, Pakistan, and the United Kingdom and recently 3 isolated cases have been found in the United States (in California, Illinois, and Massachusetts).
* Carbapenem resistance in Enterobacteriaceae is not unique to NDM-1. It is a major problem in Klebsiella pneumoniae carbapenemases (KPC), which is endemic in some areas of the United States.
* In the United States, NDM-1 would most likely first be identified in urinary tract infections, mainly among people who have exposure in healthcare settings.
* The 3 NDM-1 clinical isolates currently identified in the United States were not a result of medical tourism. However, patients who travel overseas for medical care should obtain good information on levels of quality either from the medical centers where they're going or from the people who are sending them there. A good source of information on medical tourism can be found in the CDC yellow book.
* Clinicians who identify patients with carbapenem-resistant Enterobacteriaceae, especially in a nonendemic area, should inquire specifically about whether that patient has been abroad to India or Pakistan and whether he or she received medical care there. Then, the clinician should forward on to their state labs and CDC any isolates associated with travel and medical care in those countries.
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