EID: Environmental NDM-1 Detected In Vietnam

Inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria. – CDC PHIL.

 

# 6440

 

In a study reminiscent of one we saw published in April of last year (see Lancet Study: NDM-1 In New Delhi Water Supply), the CDC’s EID Journal has a letter by R. Isozumi et al. that appears (ahead of print) in their August issue, that reveals the detection of the NDM-1 gene in a river in Hanoi.

 

bla_NDM-1–positive Klebsiella pneumoniae from Environment, Vietnam

Rie Isozumi , Kumiko Yoshimatsu, Tetsu Yamashiro, Futoshi Hasebe, Binh Minh Nguyen, Tuan Cuong Ngo, Shumpei P. Yasuda, Takaaki Koma, Kenta Shimizu, and Jiro Arikawa

 

By way of explanation, bla_NDM-1 is the gene responsible for creating the NDM-1 (New Delhi metallo-β-lactamase) enzyme that can make many types of bacteria resistant to a wide spectrum of antibiotics.

 

Of particular concern, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

 

Over the past few years we have seen a worrisome expansion of β-lactamase enzymes in bacteria, and they are slowly eroding the value of much of our antibiotic arsenal.

 

Those that inhibit the antimicrobial actions of the (formerly resistant) Carbapenem class of antibiotics – called carbapenemases – are of particular concern. Carbapenems are often used as the drug of last resort for treating difficult bacterial infections, including Escherichia coli (E. coli) and Klebsiella pneumoniae.

 

So when the gene responsible for the NDM-1 enzyme begins to show up in the environment, doctors and researchers take notice.

 

The author’s of today’s EID Journal report state their reasons for concern:

 

The possible appearance of bacteria harboring bla_NDM-1 in Vietnam is of concern because cultural and economic links between Vietnam and India are strongly established, including extensive person-to-person exchanges that could enable easy exchange of pathogens. In addition, Vietnam faces a serious problem of antimicrobial drug resistance because drugs are freely available and used in an indiscriminate fashion. Thus, once bla_NDM-1–positive bacteria colonize persons in Vietnam, they would be able to spread easily and pose a serious public health threat.

 

To look for environmental bla_NDM-1, researchers examined water samples taken from 20 locations within 10 km of Hanoi, Vietnam. Samples were collected from rivers, lakes, and standing water in the streets.

The authors report finding the NDM-1 enzyme producing gene in two locations – 3km apart – in the Kim Nguu River, which flows through the city.  They write:

 

We harvested several species of bacteria from the 2 seepage samples positive for bla_NDM-1: Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, P. fluorescens/putida, and P. luteola. 

 

They also report finding 2 other βeta-lactamases (bla_TEM-1 and bla_CTX-M-3) that were highly resistant to another class of antibiotics called aminoglycosides (which include neomycin, streptomycin & tobramycin)

The authors conclude by saying:

Wide-scale surveillance of environmental and clinical samples in Vietnam and establishment of a strategy to prevent further spread of bla_NDM-1 are urgently needed.

It’s been nearly 2 years since The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al. that awakened the world to the  emergence and growing prevalence of the NDM-1 enzyme.

 

Since that time, we’ve seen a slow, but inexorable spread of NDM-1 carrying bacteria around the globe. A few of my past blogs on the subject include:

 

Carbapenemases Rising

NDM-1: One Year Later

WHO Unveils 6-Point Plan To Preserve Antibiotic Effectiveness

Eurosurveillance On Antimicrobial Resistance

 

For a far more complete discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA. And Maryn’s SUPERBUG Blog, part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.

 

Last March, Director-General of the World Health Organization Margaret Chan warned that the World Faces A `Post-Antibiotic Era’. One where even common infections may become untreatable.

 

While we aren’t there yet, reports such as the one today in the EID Journal add to the growing concern that someday, that fear may become a reality.

»» Read More

CMAJ: Local Acquisition Of NDM-1 In Ontario

 

 

 

 

# 5585

 

My thanks to Crof for the head’s up on this study which just appeared in the CMAJ, that looks at two cases of NDM-1 recently detected in Ontario – one of which appears to have been locally acquired.

 

NDM-1, or New Delhi metallo-ß-lactamase-1, is an  enzyme that can confer resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems.

 

Of particular concern, the gene (bla_NDM-1) that encodes this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be horizontally transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

 

The NDM-1 enzyme made headlines last August when a Lancet Infectious Diseases article was published on its growing prevalence on the Indian sub-continent and its recent importation into the UK, US, and other countries.

 

In April of 2011, the same researchers published a new study (again in The Lancet) that found the NDM-1 enzyme in 4% of New Delhi’s sampled drinking water sources, and 30 per cent of the sewage tested (see Lancet Study: NDM-1 In New Delhi Water Supply) and perhaps most importantly – identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

 

While there have been scattered instances of NDM-1 bacterial infections detected in the United States and in Canada, practically all of them can be traced back to travel to India or Pakistan.

 

Today’s report in the Canadian Medical Association Journal highlights two cases of NDM-1 urinary tract colonization in Canada. In each case the patients were asymptomatic, no further spread (in-hospital or to family contacts) was detected, and antibiotics were withheld to avoid giving the bacteria an opportunity to develop further resistance.

 

One subject had recently traveled to India, while the other had not traveled outside of Ontario for at least 10 years and is believed to be the first documented instance of local acquisition of NDM-1.

 

Additionally, both cases involved bacterial strains (Morganella & Providencia) not normally associated with NDM-1, and both cases illustrate the difficulties in identifying organisms that produce NDM-1 with current laboratory testing protocols.

 

You can read the details in:

 

New Delhi metallo-ß-lactamase-1: local acquisition in Ontario, Canada, and challenges in detection

Julianne V. Kus, Manal Tadros, Andrew Simor, Donald E. Low, Allison J. McGeer, Barbara M. Willey, Cindy Larocque, Karen Pike, Iris-Ann Edwards, Helen Dedier, Roberto Melano, David A. Boyd, Michael R. Mulvey, Lisa Louie, Christopher Okeahialam, Mark Bayley, Cynthia Whitehead, Denyse Richardson, Lesley Carr, Fatema Jinnah and Susan M. Poutanen

 

 

Today’s report should not inspire undo public alarm, as the risk to the public is very low. This should, however, serve as a reminder to hospitals and health care facilities that NDM-1 is a growing concern.

 

Doctors will now have to consider that a history of recent foreign travel, while still the most common route of NDM-1 acquisition in North America, is no longer a firm prerequisite for infection.

 

And hospitals will have to gear up to deal with the the patient screening and infection control challenges that a new resistant pathogen presents, while laboratories will have to develop new testing protocols.

 

The NDM-1 enzyme was first identified in a Klebsiella pneumoniae isolate from a native of India, who was then a resident in Sweden, just three years ago. Since then it has been detected in bacteria in India, Pakistan, the United Kingdom, the United States, Canada, Japan and Brazil.

 

While the end of the antibiotic era is not yet at hand, the fear is we may be drawing closer to that day.  Which is why we watch reports of bacterial resistance with such great interest.

 

For a far more complete (and eye-opening) discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA.

 

And Maryn’s SUPERBUG Blog, now part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.

»» Read More

NDM-1 Surveillance

 

 

# 4880

 

 

 

Just short of a month ago a new form of antibiotic resistance called New Delhi metallo-ß-lactamase-1, or NDM-1 for short, made headlines in the wake of the release of a Lancet study called:

 

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

 

Like many health bloggers, I wrote several times on this mutated gene that can confer resistance to some types of gram negative bacteria against our most powerful antibiotics.

 

NDM-1: A New Acronym To Memorize

Public Health Agencies On NDM-1

Denialism and NDM-1

 

But arguably the best coverage came from Maryn McKenna on her Superbug Blog  here and here. 

 

Since then, we’ve seen a few scattered media reports of cases of NDM-1 that have been detected in nations around the world, some political outrage and posturing from India regarding the naming of the gene, and little else of note.

 

Unlike a pandemic, which can explode around the world in a matter of weeks or months - this is going to be a slower evolving story.

 

It may take years for NDM-1 to become widespread – so news stories right now are mostly about the potential threat. 

 

Which brings us to a pair of reports today, one out of Japan and the other out of Taiwan, regarding surveillance for this new health threat.

 

 

First, from  Agence France Presse we get a report on Japan’s intention to conduct a nationwide survey on NDM-1, after their Health Ministry confirmed their first case last week.

The Health Minister also announced a tightening of hospital reporting requirements.

 

Japan plans nationwide survey for NDM-1 superbug

(AFP)

 

 

Although Taiwan has yet to identify any residents with NDM-1, their CDC (Center for Disease Control) announced today that they have classified this newly identified form of antibacterial resistance as a reportable communicable disease.

 

Doctors and hospitals are now required to notify the Taiwanese CDC if they encounter any suspected NDM-1 cases, particularly if a patient has returned from Pakistan or India.

 

More details are available from this Focus Taiwan news article.

 

CDC to list new superbug NDM-1 as communicable disease

2010/09/07 15:56:59

 

 

It should be noted that Japan’s only known case of NDM-1 resistance came from a man in his 50’s who was hospitalized in April 2009 after returning from India with a high fever.

 

He remained hospitalized until October of last year, and then was discharged.  

 

After The Lancet article was published last month, staff at the Dokkyo Medical University Hospital went back and examined a preserved sample from the patient, and identified the NDM-1 gene.

 

Media reports indicate the patient has since been tested for the NDM-1 gene, and found clear. The hospital also states that the infection did not spread within their facility.

 

While `breaking news’ stories are few and far between regarding NDM-1, the evidence suggests that the gene is spreading slowly, but insidiously around the world.

 

Over time, a combination of good surveillance and solid scientific analysis should give us a much better idea about the scope of the threat posed by this newly emerging antibiotic resistant gene.

»» Read More

India Looks For (And Finds) NDM-1

 

 

 

# 5521

 

 

Inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria. – CDC PHIL.

NDM-1, or New Delhi metallo-ß-lactamase-1, is an  enzyme that can confer resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems.

 

Of particular concern, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

 

 

Last August a Lancet Infectious Diseases article was published on its growing prevalence on the Indian sub-continent and its recent importation into the UK, US, and other countries.

 

 

The Lancet Infectious Diseases, Early Online Publication, 11 August 2010

doi:10.1016/S1473-3099(10)70143-2Cite or Link Using DOI

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

 

 

The reaction from officials out of India was both immediate and disappointing. Rather than taking action against a growing public health threat, they took umbrage instead.

 

They condemned of the use of `New Delhi’ in the naming of this resistance gene, called the paper a `conspiracy theory’, and issued broad denials of its prevalence in India or that medical tourism to their nation was responsible for its spread.

 

It is worth noting that the naming convention for pathogens that invoked so much ire traditionally incorporates its place of discovery or emergence.

 

In 2001 a similar gene was discovered in Brazil and was dubbed SPM-1 (Sao Paulo metallo-beta-lactamase). Another, discovered in 1999 in Italy, is called VIM (Verona integron-encoded metallo-β-lactamase), while SIM stands for Seoul imipenemase found in Korea.

 

Six months later (April, 2011), the same researchers published a new study, again in The Lancet, that found the NDM-1 enzyme in 4% of New Delhi’s sampled drinking water sources, and 30 per cent of the sewage tested.

 

The Lancet Infectious Diseases, Early Online Publication, 7 April 2011

doi:10.1016/S1473-3099(11)70059-7

Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study

Prof Timothy R Walsh PhD , Janis Weeks BS, David M Livermore PhD , Mark A Toleman PhD

 

And as feared, the researchers also identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

 

Once again the reaction out of India was one of swift denial (see Hopefully, It’s Just A Stage They Are Going Through). 

 

Indian newspapers, however, have continued to question the government’s response - putting pressure on officials to begin testing for the enzyme.

 

Over the past couple of days Indian media has carried reports out of Pune - a city of about 3.5 million (8th largest in India) located about 1400 kilometers from New Delhi – regarding the detection of 20 NDM-1 cases at Sassoon hospital.

 

Pune is less than 200 kilometers from Mumbai (formerly Bombay), which is the largest city in India (12.5 million people) and the 5th largest metropolitan area in the world.

 

Microbiologists tested samples of blood, urine and puss from 3,172 patients at the hospital and found that 885 had gram negative bacterial infections. 

 

Of those, 181 (20%) were resistant to the carbapenem family of drugs .

 

And twenty of those tested positive for the NDM-1 gene.

 

Some of the media coverage follows. From the Indian Express we get:

 

NDM-1 in Pune: Researchers

Posted: Sat Apr 23 2011, 01:11 hrs Pune:

‘Superbug gene detected in 20 patients’

The controversial multi-drug-resistant superbug, the origin of which has been a matter of debate with the Centre taking strong exception to it being named after New Delhi, researchers from the government-run B J Medical College (BJMC) and the National Centre for Cell Science (NCCS), in preliminary findings of a study to find the New Delhi metallobeta lactamase-1 (NDM-1) incidence in Pune, reported the strain in the city.

(Continue . . . )

 

And from Mid-Day News:

 

 

NDM-1 superbug has arrived in the city

By: Alifiya Khan
Date:  2011-04-25
Place: Pune

20 of 885 patients tested by Sassoon hospital found infected by antibiotic-resistant bug controversially named after Indian capital, says dean of govt healthcare facility

THE NDM-1 superbug has reached the city. So far 20 patients from Sassoon General Hospital have shown the presence of the multi-drug-resistant superbug. Shocking as it may sound, the presence of the New Delhi metallobeta lactamase-1 (NDM-1) superbug in the city is a fact that has been confirmed by the seniormost authority at the hospital.

(Continue . . . )

 

 

Absent from these media dispatches are details on the exact types of resistant bacteria that were detected.   

 

While 20 NDM-1 cases may not sound like a lot, these are the results from only 1 hospital over a 2-month period of time.  

 

It undoubtedly only represents the tip of the iceberg.

 

And as I described in my blog Carbapenemases Rising, the rising rate of regular carbapenem resistance is alarming as well.  Carbapenems are often used as the drug of last resort for treating difficult bacterial infections, including Escherichia coli (E. coli) and Klebsiella pneumoniae.

 

India, of course, isn’t the only country with NDM-1 cases or growing carbapenem resistance - although the Indian sub-continent does appear to be a focal point – a situation often blamed on their longstanding lax controls on the use of antibiotics.

 

Given the results of these studies published in the Lancet, and these latest findings from Pune’s Sassoon hospital - increased surveillance, openness, and international cooperation  – not indignation – are the responses needed today if a major public health crisis is to be averted.

 

One that has the potential to spread far beyond India, and that could – over time – greatly diminish our ability to fight bacterial infections with our dwindling arsenal of antibiotics.

 

For more on NDM-1 and antimicrobial resistance, you may wish to check out:

 

• Eurosurveillance On Antimicrobial Resistance

• ECDC/EMEA: Joint Report On Resistant Bacteria

• Carbapenemases Rising

• WHO: The Threat Of Antimicrobial Resistance

• NDM-1: A New Acronym To Memorize

 

 

And perhaps the single best place to learn about the dangers and impact of antimicrobial resistance is from our favorite `scary disease girl’ Maryn McKenna’s SUPERBUG BLOG  and her terrific book on the subject  SUPERBUG: The Fatal Menace Of MRSA.

 

»» Read More

NDM-1: A New Acronym To Memorize

 

 

UPDATE: 8/14/10    This has turned into a rapidly evolving story.  To see a list of the latest blog entries on NDM-1 click this link.

 

 

UPDATE: 1900 hrs EST 8/11/10    Maryn McKenna has posted this evening on NDM-1 on her Superbug blog, going into far more depth and detail than I have here.

 

By all means, you’ll want to read her post  NDM-1: Novel, global, complex and a serious threat.

 

 

# 4796

 

 

New Delhi metallo-ß-lactamase-1, or NDM-1, is an  emerging enzyme that can confer resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems.

 

Carbapenems are newer generation beta-lactam antibiotics (a class that includes penicillins, cephalosporins, cephamycins, and carbapenems) that are usually reserved as an antibiotic of last resort.

 

Up until recently, Carbapenems have been generally resistant to Beta-lactamases - enzymes bacteria use to breakup the ring structure of “beta-lactam” antibiotics - that renders them ineffective.

 

But in recent years a new enzyme has been spreading in India, Bangladesh, and Pakistan that helps certain types of bacteria to defeat Carbapenem antibiotics; NDM-1.   

 

Although NDM-1 has been around for some time, it is making the news today after the release of a Lancet Infectious Diseases article on its growing prevalence on the Indian sub-continent and its recent importation into the UK, US, and other countries.

 

Travelling abroad for elective (usually cosmetic) surgery has become much in vogue in Europe and the United States, and that has created an opportunity for this enzyme to spread.

 

While the numbers being reported in the UK are still small, one of the concerns is that this enzyme may find its way into other gram negative bacteria that may already have partial resistance to other classes of antibiotics, which could create a new multi-drug resistant superbug.

 

The Lancet Infectious Diseases, Early Online Publication, 11 August 2010

doi:10.1016/S1473-3099(10)70143-2Cite or Link Using DOI

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

(EXCERPT)

Findings

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. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse.

 

Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries.

 

Interpretation

The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.

 

 

For more on this story, the BBC has a Q&A style report at: Q&A: NDM-1 superbugs  and Reuters reports in Scientists find new superbug spreading from India.

 

Some of the other media reports I’ve seen this morning are unnecessarily hyperbolic, although the potential threat is quite real. 

 

Antibiotics are fleeting victories against bacteria at best, since from the minute they are introduced, bacteria begin to evolve ways to defeat them.  

 

With very few new antibiotics in the pipeline, the world is in genuine danger of facing a future with far fewer resources to combat infections.

 

Short of seeing a devastating pandemic, this may well be the `big’ medical story of the next couple of decades.

 

Given the gravity of the situation, I can think of no better introduction to the world of antibiotic resistance than Maryn McKenna’s superb Superbug: The Fatal Menace of MRSA, which I reviewed last March.

If you haven’t already read it, I highly recommend it.

 

 
My Review of SUPERBUG

»» Read More

Lancet Study: NDM-1 In New Delhi Water Supply

 

 

# 5470

 

Released just in time for World Health Day, we’ve a fresh study that appears in The Lancet authored by Timothy Walsh, Janis Weeks , David M Livermore, and Mark A Toleman that looked for – and found – bacteria carrying the NDM-1 enzyme in New Delhi's drinking water supply.

 

NDM-1, or New Delhi metallo-ß-lactamase-1, is an  enzyme that can confer resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems.

 

Carbapenems are newer generation beta-lactam antibiotics (a class that includes penicillins, cephalosporins, cephamycins, and carbapenems) that are usually reserved as an antibiotic of last resort.

 

Up until recently, Carbapenems have been generally resistant to Beta-lactamases - enzymes bacteria use to breakup the ring structure of “beta-lactam” antibiotics - that renders them ineffective.

 

But in recent years a new enzyme has been spreading in India, Bangladesh, and Pakistan that helps certain types of bacteria to defeat Carbapenem antibiotics; NDM-1.

 

Although the NDM-1 enzyme has been around since about 2008, it made headlines last August when a Lancet Infectious Diseases article was published on its growing prevalence on the Indian sub-continent and its recent importation into the UK, US, and other countries.

 

Professor Timothy Walsh, along with two of the co-authors of today’s report (David M Livermore , Mark A Toleman) were among the authors of this original Lancet study.

 

The Lancet Infectious Diseases, Early Online Publication, 11 August 2010

doi:10.1016/S1473-3099(10)70143-2Cite or Link Using DOI

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

 

 

Since that time the NDM-1 gene has been the subject of much scientific scrutiny and enhanced surveillance, particularly since it often carried on a plasmid – a snippet of DNA - that has the potential to jump to other strains of bacteria.

 

Although most cases reported in Europe and North America have travel links to Southeast Asia, that can’t be said for all of them.

 

Last November Maryn McKenna explored the apparent community spread of the bacteria in NDM-1, the supergene: Further (community?) spread.

 

We’ve a press release on today’s study, issued by Cardiff University, that gives the highlights of the study, but the `money quote’ (emphasis mine) buried about halfway down is:

 

Resistant bacteria were found in 4 per cent of the water supplies and 30 per cent of the seepage sites. The researchers identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

 

The spread of the NDM-1 gene to 11 new strains of bacteria is particularly ominous news.

 

In an interview for Reuters today, co-author Mark Toleman of Britain’s Cardiff University School of Medicine stated that as many as 500,000 residents of New Dehli may be carrying the NDM-1 resistance gene in their gut flora.

 

 

Antibiotic-resistant bacteria in Indian public water supply

Disease-causing bacteria carrying the new genetic resistance to antibiotics, NDM-1, have been discovered in New Delhi's drinking water supply.

 

A Cardiff University-led team found new strains of resistant bacteria in the Indian capital, including species which cause cholera and dysentery. The findings are the first evidence of the environmental spread of NDM-1, which had previously only been found in hospitals.

 

The scientists are calling for urgent action by health authorities worldwide to tackle the new strains and prevent their global spread. The Cardiff scientists also highlight the all-round benefits of preventative measures such as better sanitation and appropriate drinking water.

 

Cardiff scientists were the first to identify the NDM-1 gene which makes bacteria resistant to a large range of antibiotics. Moreover, the NDM-1 gene is carried on mobile DNA called plasmids which can carry up to 13 other antibiotic resistance genes. While most patients with the bacteria have recently been hospitalised in India, some cases have occurred there without recent hospital treatment, prompting the team to test the wider environment.

 

Samples were taken in New Delhi from public water taps and from waste seepage, such as water pools in the street. Resistant bacteria were found in 4 per cent of the water supplies and 30 per cent of the seepage sites. The researchers identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentry.  Antibiotics are used to reduce excretion of bacteria in cholera patients, and to reduce the duration and severity of dysentery. Worryingly, the identified Shigella isolate, which can carry dysentery, is resistant to all appropriate antibiotics.

 

Study leader Professor Tim Walsh, of Cardiff University's School of Medicine, said: "These are extremely worrying results. We found resistant bacteria in public water used for drinking, washing and food preparation and also in pools and rivulets in heavily-populated areas where children play. The spread of resistance to cholera and to a potentially-untreatable strain of dysentery is also a cause for extreme concern."

(Continue . . . )

 

 

Below is a link to the Lancet study, which you can read in its entirety (a free registration is required).

 

The Lancet Infectious Diseases, Early Online Publication, 7 April 2011

doi:10.1016/S1473-3099(11)70059-7Cite or Link Using DOI

 

Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study

Prof Timothy R Walsh PhD , Janis Weeks BS, David M Livermore PhD , Mark A Toleman PhD

 

Interpretation

The presence of NDM-1 β-lactamase-producing bacteria in environmental samples in New Delhi has important implications for people living in the city who are reliant on public water and sanitation facilities. International surveillance of resistance, incorporating environmental sampling as well as examination of clinical isolates, needs to be established as a priority.

(Continue . . . )

 

 

Antibiotics have often been called the miracle drugs of the 20th century, but almost from their inception bacteria have been evolving and finding ways to evade them. 

 

In 1940, even before penicillin could be rolled out for clinical use, the first β-lactamase (Penicillinase) was identified by researchers in a sample of Gram-negative E. coli.

 

Over the next two decades this penicillinase resistance spread to other bacteria, which required the creation of newer generations of penicillin (such as Methicillin in 1959), that were resistant to these enzymes.

 

Methicillin is no longer used (replaced by newer generation antibiotics), although we retain its name in the term MRSA (Methicillin-resistant Staphylococcus aureus), which was identified in the UK just two years after Methicillin was introduced.

 

Today, we are seeing an ever expanding array of antimicrobial resistant bacteria and a worrying lack of new drugs in the development pipeline to deal with them.

 

Which is why the World Health Organization has declared that the focus on this year’s World Health Day (April 7th) to be on this growing threat.

 

You can read more on this global observance in my blog  World Health Day 2011.

»» Read More

CHP: Review Of NDM-1 In Hong Kong

Inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria. – CDC PHIL.

 

# 6719

 

The Centre for Health Protection publishes a weekly Communicable Disease Watch, where they highlight recent infectious disease events in and around Hong Kong.

 

Today, they include a review of the resistance enzyme NDM-1 (New Delhi metallo-ß-lactamase-1) which was first detected in a patient in Sweden (albeit with Indian origins) four years ago, but has subsequently spread to many countries around the world.

 

This enzyme confers resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems. Carbapenems are often our drug of last resort against a variety of bacterial infections.

 

Of particular concern, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

 

The rise of antibiotic resistance - including this emerging NDM-1 enzyme - has long been linked to the overuse and misuse of antibiotics. A practice that is still widespread in many parts of the world, but is particularly rampant on the Indian sub-continent.

 

Citing a lack of doctors and low family incomes, the Indian government (see India: Still Looking For A Policy On Antibiotics) has been slow to stop the sale of antibiotics to the public without a doctor’s prescription.

 

It’s been more than 2 years since The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al. that sounded the alarm on the emergence and growing prevalence of the NDM-1 enzyme on the Indian sub-continent.

 

Since that time, we’ve seen a slow, but inexorable spread of NDM-1 carrying bacteria around the globe. A few of my past blogs on the subject include:

 

Carbapenemases Rising

NDM-1: One Year Later

WHO Unveils 6-Point Plan To Preserve Antibiotic Effectiveness

Eurosurveillance On Antimicrobial Resistance

 

 

Today’s report from the HPC indicates that they have identified 17 patients carrying the NDM-1 enzyme over the past four years, with one case each in 2009 and 2010, three cases in 2011, and 12 cases so far in 2012.

 

Many of these cases were colonized and detected through routine screening, but were asymptomatic. As this report indicates:

 

Infections varied from colonisation or mild to potentially life threatening or fatal. The level of risk depends upon which body part is infected and general health of the patient.

 

I’ve included some excerpts, but follow the link to read:

 

 

Source CHP Communicable Disease Watch

Among the 17 cases, 13 (76%) were male, and the median age was 64 years (ranged from 11 months to 94 years). Fourteen (82%) were Chinese, 2 Indian and 1 Burmese.

 

Among 16 imported cases, all except one had history of admission to hospitals while staying abroad. Twelve were hospitalised in Mainland China (8 in Guangdong province, 2 in Hunan province, 1 in Fujian province and 1 in Henan province), one in India, one in Myanmar and one in Thailand. Six (40%) of them had operations done during their hospitalisation.

 

The one without history of admission to hospital was a 66-year-old male patient of Indian ethnicity and he had travelled to India before onset of symptoms. Four cases had signs of infection (2 had chest infection, 1 urinary tract infection and 1 leg infection). 

 

Thirteen were asymptomatic colonisation detected by screening or contact tracing. One had the bacteria yielded from both sputum and rectal swab specimens. Two cases passed away due to underlying illness and aspiration pneumonia respectively.

 

In September 2012, CHP identified an import-related NDM-1 case affecting a 64-year-old man. A rectal swab was taken for this patient as part of the contact tracing exercise for another imported NDM-1 patient (78-year-old man) from Myanmar. They had stayed in the same cubicle of a hospital ward in Hong Kong.

 

The rectal swab was tested positive for NDM-1. Pulsed-field gel electrophoresis patterns of the two NDM-1 strains were subsequently found to be identical by the Public Health Laboratory Services Branch (PHLSB) of CHP.

This suggests that the 64-year-old case was epidemiologically linked to the 78-year-old imported case. Thirteen other patients stayed in the same cubicles as the case patients for more than 48 hours were screened by rectal swabs and all were tested negative.

 

 

This week is antibiotic awareness week (see A Health Crisis In Slow Motion) here in the United States, as it is in many places around the world. The erosion of the effectiveness of our antimicrobial arsenal increases with each year, and leads many doctors and scientists to worry that we’ll eventually lose the ability to treat even common infections.

 

For a far more complete discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA. And Maryn’s SUPERBUG Blog, part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.

»» Read More

South African Statement On NDM-1 Cases

 

Inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria. – CDC PHIL.

 

# 5915

 

Over the past week a story emerged from South Africa regarding (initially 9, now 10) patients in a private hospital who were diagnosed with an NDM-1 bacterial infection.

Crof, at Crofsblog covered these reports here, here, and here.

 

Three of these patients have reportedly died, but local authorities have pointed out that all three had `co-morbidities’ that probably played a major role in their deaths.

 

NDM-1 gained prominence a little over a year ago with the publication of a Lancet article (see NDM-1: A New Acronym To Memorize) that tied India and Pakistan to the emergence and spread of an enzyme that confers resistance in common gram negative bacteria like E.coli and Klebsiella against most antibiotics.

 

Today the South African Department of Health has posted a statement regarding these recent cases. While calling NDM-1 a `national concern’, it provides little in the way of specifics on this outbreak, and instead seeks to reassure that everything is under control.  

 

 

Emergence of NDM-1 in South Africa a national issue

Joint media statement issued by the National Department of Health and Life Healthcare

20 October 2011

 

The emergence of the Klebsiella pneumoniae producing NDM-1 enzyme in South Africa is a matter of national concern. It should be noted that the institution-based outbreak is contained through the effective measures implemented thus far. The possibility of further spread is limited.

 

NDM-1 was identified at Life The Glynnwood Hospital in Benoni, where 10 patients treated were confirmed to have NDM-1. An outpatient at Charlotte Maxeke Hospital in Johannesburg was earlier also confirmed with this multidrug resistant strain of bacteria. There are presently still three patients in Glynnwood Hospital with the NDM-1 bacterium who are in a stable condition.

 

Representatives of the national, provincial and district departments of health met with Life The Glynnwood management and with representatives of Life Healthcare (of which the hospital forms part) as well as with other key roleplayers on Wednesday (19 October) to assess the situation and determine the way forward.

 

Life The Glynnwood was commended for identifying the NDM-1 strain promptly and implementing effective interventions to respond to the outbreak and prevent its spread. These measures include effective treatment and isolation of affected patients, strengthening infection control measures, screening of around 400 patients and staff as well as commissioning an independent clinical audit.

 

A co-ordinating outbreak response team was formed that will meet regularly to monitoring and redirect response to the outbreak when needed. A monitoring system within public and private sector will also be set up.

 

A formal report is being compiled and will be submitted to the Minister of Health. The parties will furthermore work together in formalising a NDM-1 treatment protocol for clinicians. They will also document lessons learned from the experience at Life The Glynnwood to share with other roleplayers. These actions will be of immense value to other hospitals which may be faced with a similar situation in future.

 

Prof Adriano Duse, an appointee of the Department of Health and the Head of Clinical Microbiology and Infection Control at Wits University as well as the National Health Laboratory Services (NHLS) will continue to be the spokesperson on the NDM-1 outbreak.

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India: The NDM-1 Story Continues

 

 

# 5880

 

 

In a follow up to Monday’s blog on the failure of the Indian government to restrict the over-the-counter sale of antibiotics, we’ve several news stories this morning that emphasize just how quickly NDM-1 and other forms of antibiotic resistance are spreading on the Indian subcontinent.

 

Many of these stories, no doubt, are inspired by this week’s global summit on antibiotic resistance being held in New Delhi. 

 

NDM-1, or New Delhi metallo-ß-lactamase-1, is an enzyme that confers antibiotic resistance to several common types of bacteria. This emerging form of antimicrobial resistance made huge headlines in a Lancet study in August of last year:

 

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

 

Of particular concern, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

 

Since then, sporadic NDM-1 cases have been identified in countries around the world, with the vast majority of them having some link to a previous medical procedure or treatment in India or Pakistan.

 

The Indian government’s response was first to deny that a problem with NDM-1 existed and to take serious umbrage over the naming of the pathogen. 

 

Under pressure to act, promises to restrict the sale of antibiotics were made in October of last year, but have yet to be implemented.

 

Again in April of this year, The Lancet published another study by Timothy Walsh, Janis Weeks , David M Livermore, and Mark A Toleman that looked for – and found – bacteria carrying the NDM-1 enzyme in New Delhi's drinking water supply.

 

Lancet Study: NDM-1 In New Delhi Water Supply

 

A snippet from the press release stated ominously (emphasis mine):

 

Resistant bacteria were found in 4 per cent of the water supplies and 30 per cent of the seepage sites. The researchers identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

 

In an interview for Reuters, co-author Mark Toleman of Britain’s Cardiff University School of Medicine stated that as many as 500,000 residents of New Delhi may be carrying the NDM-1 resistance gene in their gut flora.

 

The response from the Indian government, again, was one of denial (see Hopefully, It’s Just A Stage They Are Going Through).

 

Indian officials claimed that the researchers `illegally transferred’ samples of tap water out of the country, stated that the research was `unscientific’ and insist that the researchers were intentionally biased.

 

 

Which brings us to several stories this morning that go a long ways towards confirming many of the findings of these two much-maligned-in-India Lancet studies.

 

First stop, the The Economic Times.

 

Ganga Ram study finds high levels of superbug NDM1

5 Oct, 2011, 1114 hrs IST, Durgesh Nandan Jha, TNN

NEW DELHI: India might have vehemently opposed an antibiotic-resistant superbug being named New Delhi Metallo-beta-lactamase 1 (NDM1), but a study in a leading city hospital has found a worryingly high prevalence of the deadly gene.

(Continue . . . )

 

The study, conducted over a 5-month period, examined 10,889 samples from patients. The NDM1 resistance gene was found in 8.1% of E. coli samples and 38.02% of samples of K. pneumoniae.

 

In the article, Dr S P Byotra, chairperson of medicine at the Ganga Ram Hospital, is quoted as saying:

 

"The idea behind this study is to stop denying the crisis NDM1 poses and work out strategies to check its spread. Antibiotic usage needs to be monitored strictly and good infection-control methods should be put in place at hospitals."

 

Next, a related article in the International Business Times, that quotes Former Indian Council of Medical Research chief and chairman N.K. Ganguly saying that the multi-drug resistant New Delhi metallo-beta-lactamase-1 or NDM-1 comes from hospital waste that goes into Delhi's sewage water.

 

Presence of Antibiotic-Resistant Bacteria in Delhi Confirmed

October 5, 2011 1:26 PM EST

 

Another story, this time from IBN-Live, states that 60,000 newborns die each year in India due to various types of antibiotic resistant sepsis (including NDM-1).

 

Health | Updated Oct 05, 2011 at 11:48am IST

NDM-1 superbug hits neonatal ICUs, kills infants

 

 

And lastly, filed under the category of no-good-deed-goes-unpunished, two of the authors of the original Lancet study – Dr Timothy R. Walsh and Dr Mark Toleman – report a decidedly cool reception at this week’s global summit in New Delhi.

 

Savita Verma  New Delhi, October 5, 2011 | 

UK 'superbug' scientist-duo alleges boycott by Indian counterparts

 

Despite hosting a global summit this week, India still appears to be treating NDM-1 and antibiotic resistance as a public relations problem instead of a public health threat.

 

To be fair, India isn’t the only country with NDM-1 cases or growing carbapenem resistance. But the Indian sub-continent does appear to be a focal point – a situation often blamed on their longstanding lax controls on the use of antibiotics.

 

 

Short of seeing an extremely high mortality influenza pandemic, I can think of no looming medical crisis more dire than the growing threat of antimicrobial resistance.

 

The World Health Organization (WHO) and the CDC - along with other public health organizations around the world – used this year’s World Health Day – 7 April 2011 to promote sane antibiotic usage and awareness of antimicrobial resistance.

 

 

Given the these reports (and many others), increased surveillance, openness, and international cooperation – not indignation, intimidation, and denial – are the responses needed if we are to have any hope of stemming the rise of antibiotic resistance around the globe.

 

And we need these things now, as time is not exactly on our side.

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NDM-1 Updates From India

 

 

 

# 5021

 

 

A couple of stories this morning on NDM-1.

 

In what unfortunately may end up being a case of closing the barn door after the horse got out, India yesterday announced stricter regulations on the over-the-counter sale of antibiotics to the public. 

 

This move comes in response to recent reports of a new form of antibiotic resistance (see NDM-1 Surveillance) strongly associated with medical tourism out of India and Pakistan.

 

Actually, the first response from Indian officials was outrage that this emerging pathogen was named after New Delhi, along with a few ham-handed attempts to `spin’ the news.   

 

 

This move to restrict the sale of antibiotics comes more than two months later.

 

 

NDM-1 or New Delhi metallo-ß-lactamase-1 made headlines in the wake of the release of a Lancet study back in August called:

 

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

 

 

Since then, sporadic NDM-1 cases have been identified in countries around the world, with the vast majority of them having had some medical procedure or treatment in India or Pakistan.

 

But I digress . . . here is the first report, from DNA (Daily News & Analysis).

Superbug fallout: Antibiotics ‘on counter sale’ ceased

Published: Saturday, Oct 30, 2010, 9:00 IST
By Akanksha Bafna | Place: Mumbai | Agency: DNA

The drug controller general of India (DCGI) on Friday introduced new rules to buy antibiotics. According to the revised rules, a patient will need two copies of a prescription - one which will be in the chemist's custody.

 

(Continue . . .)

 

 

Admittedly, India required prescriptions for the purchase of antibiotics before yesterday, but a lack of enforcement meant that this was regarded more as a suggestion than a rule.

 

Indian and Pakistani pharmacies are also prominently featured in online ads hawking the sale of a variety of meds – including antibiotics – without the need for prescriptions. 

 

While these new regulations supposedly add `teeth’ to the law, the unregulated sale of antibiotics has been a lucrative business in India for some time.

 

It remains to be seen how successfully these new rules will be enforced and how effective they will be in curbing the unregulated sale and use of antibiotics.

 

From The Hindu, we get a report on a recent independent investigation conducted by Channel 4 News in the UK, where science correspondent Tom Clarke – with the aid of NDM-1 researcher Professor Timothy Walsh – tested sewage in more than 120 locations across Delhi for the NDM-1 resistant bacteria.

 

The resistant gene was detected in nearly 10% of the samples.

 

“It suggests NDM is spread all over Delhi and people are carrying (these bacteria) as part of their normal flora,” Professor Walsh was quoted as saying.

 

First the article in the Hindu, followed by a link to the Channel 4 News investigative report.

 

News channel claims superbug could be widespread in India

Aarti Dhar

A British television channel has claimed that the New Delhi metallo-B- lactamese (NDM-1) bacteria could be widespread in Indian cities.

(Continue. . . )

 

 

The Channel 4 News story, with more detail, including reports of political interference in the Lancet research:

 

Drug Resistant Superbug Threatens UK Hospitals

Thursday 28 October 2010

Tom Clarke Science Correspondent

Efforts to contain a new strain of superbug threatening the NHS and other health authorities around the world may almost be unachievable, exclusive research by Channel 4 News reveals.

(Continue . . . )

 

 

Unlike a flu pandemic – which can spread very quickly – antibiotic resistance moves at a more glacial pace.  MRSA, after all, was first identified in the early 1960s in the UK, but didn’t really become a huge public health problem for a couple of decades.

 

Today, with global travel and medical `tourism’ far more common, resistant organisms have more opportunities to spread - and so while it may still take awhile – newly emerging resistant bacteria are likely to spread faster than we’ve seen in the past.

 

All of which makes NDM-1 an important long-term story to watch.

 

Like many health bloggers, I’ve written a number of times on this emerging mutated gene. A few of my previous efforts include:

 

NDM-1: A New Acronym To Memorize

Public Health Agencies On NDM-1

Denialism and NDM-1

 

Arguably, some of the best coverage has come from our favorite `scary disease girl’ Maryn McKenna editor of the Superbug blog.

 

And if you’ve not already read Maryn’s 2nd book, Superbug: The Fatal Menace of MRSA, I would invite you to do so.

 

Superbug (MRSA) Book

Although published before the identification of the NDM-1 threat, this book remains a chilling and informative look at the growing problem of emerging antimicrobial resistance.

 

My review of it may be read here.

 

Highly recommended.

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Hopefully, It’s Just A Stage They Are Going Through

 

 

 

All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.

Arthur Schopenhauer
German philosopher (1788 - 1860)

 

 

Even as evidence of the spread of the NDM-1 resistance enzyme in India grows, Indian health officials and politicians are adamant in their denials that:

 

1) a problem exists  and

2) if a problem does exist, that it is in any way unique to India.

NDM-1, or New Delhi metallo-ß-lactamase-1, is an  enzyme that can confer resistance to certain gram negative bacteria like E.coli and Klebsiella against a class of antibiotics called carbapenems.

 

Last August a Lancet Infectious Diseases article was published on its growing prevalence on the Indian sub-continent and its recent importation into the UK, US, and other countries.

 

The Lancet Infectious Diseases, Early Online Publication, 11 August 2010

doi:10.1016/S1473-3099(10)70143-2Cite or Link Using DOI

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

 

The immediate reaction out of India was disappointing.  Condemnation of the use of `New Delhi’ in the naming of this resistance gene, and broad denials that medical tourism to India was responsible for its spread.

 

The naming convention for pathogens typically invokes its place of discovery or emergence. 

 

In 2001 a similar gene was discovered in Brazil and was dubbed SPM-1 (Sao Paulo metallo-beta-lactamase). Another, discovered in 1999 in Italy, is called VIM (Verona integron-encoded metallo-β-lactamase), while SIM stands for Seoul imipenemase found in Korea.

 

Last August Indian officials took umbrage over the naming of NDM-1, called the claims of its emergence and spread from India a `conspiracy theory’, and rejected The Lancet paper out of hand.

 

12 August 2010 Last updated at 10:44 ET

India rejects UK scientists' 'superbug' claim

By Geeta Pandey BBC News, Delhi

India has rejected a claim by British scientists that a new superbug, resistant to even the most powerful antibiotics, has entered UK from India.

(Continue . . . )

 

The rest of the world, however, was less sanguine (see Public Health Agencies On NDM-1) regarding NDM-1’s spread..

 

 

Since that time the NDM-1 gene has been the subject of much international concern, particularly since it can be carried on a plasmid – a snippet of DNA - that has the potential to jump to other strains of bacteria.

 

Last week the original authors of the NDM-1 study came forth with new data in The Lancet that found evidence of the resistance enzyme in New Delhi’s tap water and sewage sites.

 

They also found evidence that this enzyme had been passed on to 11 other types of bacteria (see  Lancet Study: NDM-1 In New Delhi Water Supply).

 

Indian reaction to this latest paper has been swift and strong, with new denials that a problem exists, or that NDM-1 posed a public health threat in New Delhi.

 

This from The Economic Times.

 

11 Apr, 2011, 02.55PM IST,PTI

India being wrongly blamed for bacteria in drinking water

NEW DELHI: Accused of "supressing the truth" about drug resistant bacteria reportedly found in Delhi's public water supply, the Union Health Ministry today said India was being "unnecessarily and wrongly blamed" and singled out in the matter.

(Continue . . . )

 

 

Indian officials have claimed that the researchers `illegally transferred’ samples of tap water out of the country, have stated that the research was `unscientific’ and insist that the researchers are intentionally biased.

 

The stakes for Indian officials are admittedly high, as medical tourism is a profitable sector of the economy and continual discussion of emerging `superbugs’ cannot possibly enhance their medical reputation.

 

Additionally, the costs of trying to rectify deficits in New Delhi’s water and sewage systems (and those elsewhere across the nation) would be enormous and prohibitive.

 

The authors of the study remain adamant that their findings are correct, and that the Indian government is `in denial’ and suppressing information.

 

This from The Statesman.

 

India suppressing truth about NDM-1: Lancet

10 April 2011

NEW DELHI, 10 APRIL: Notwithstanding the Union government’s persistent denials of the presence of a drug-resistant bacteria in the public water system, an international health journal Lancet has charged the government with “suppressing truth” about the presence of a drug-resistant bacteria in Delhi’s public water system by “threatening” and “abusing” its own scientists. It has dubbed the government’s denial of presence of such a bacteria as “unfortunate” .

(Continue . . .)

 

 

While one could certainly debate the `sensitivity’ of naming pathogens after their place of discovery, the fact is that is a long-standing convention used worldwide (ie. West Nile Virus, St. Louis Encephalitis, Hong Kong Flu, Asian Flu,  etc.).

 

The Indian strategy of `shooting the messenger’ solves nothing, and delays in determining the scope of the problem could end up costing many lives.

 

Rather than simply maligning the researchers, now is the time for Indian officials to call for an open, independent, and outside investigation into the NDM-1 threat in India. 

 

Only then can the truth be satisfactorily determined.

 

The problem with Arthur Schopenhauer’s quotation is that it can take a long time to reach the third stage – accepting the truth as being self-evident.

 

Time, that frankly, the world can ill afford to waste.

»» Read More