First Imported Case Of NDM-4 Reported In Hong Kong

 CDC Guidance For Control Of CRE

 

# 6858

 

 

In August of 2010 The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al. chronicling the emergence and spread from the Indian sub-continent of a new enzyme – dubbed  NDM-1 (New Delhi metallo-ß-lactamase-1) - 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 (that includes imipenem, meropenem, doripenem, and ertapenem) that are usually reserved as an antibiotic of last resort.

 

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, scattered variants of NDM-1 have begun to emerge;  NDM-2, NDM-4, and NDM-5.

 

Last September, an EID Journal letter called New Delhi Metallo-β-Lactamase 4–producing Escherichia coli in Cameroon, gave a description of the recent rise of these new variants.

 

Since 2010, 3 NDM-1 point-mutation variants have been described (3–5). The first variant, NDM-2, was identified from an Acinetobacter baumannii isolate collected from a patient transferred from a hospital in Egypt to Germany (4).

 

Subsequently, a clonal dissemination of NDM-2–producing A. baumanni was described in Israel (6). The second variant, NDM-4, which was identified in Escherichia coli from a patient hospitalized in India, possessed a higher carbapenemase activity compared with NDM-1 (5).

 

The most recent variant, NDM-5, was identified in E. coli from a patient who had a history of hospitalization in India (3).

 

 

While detections of these NDM variants remain rare, today Hong Kong announced their first detection of NDM-4 in a patient recently returned from India.

 

Case of NDM-4 Carbapenemase-producing enterobacteriaceae under CHP investigation

 

Tuesday, January 15, 2013
Issued at HKT 20:06

The Public Health Laboratory Services Branch (PHLSB) of the Centre for Health Protection (CHP) of the Department of Health confirmed today (January 15) a case of New Delhi metallo-β-lactamase-4 (NDM-4) Carbapenemase-producing Enterobacteriaceae in a 73-year-old man.

 

The patient with chronic illness travelled to New Delhi, India, on December 26, 2012. He developed symptoms of fever, shortness of breath and productive cough on December 28 and therefore sought medical attention at a local hospital without hospitalisation.

 

Upon arrival in Hong Kong, he sought medical consultation from another private doctor on January 3, 2013 and was admitted to Princess Margaret Hospital (PMH) on January 8. The clinical diagnosis was bronchitis and he was discharged on January 10. His condition remains stable.

 

The patient's rectal swab grew NDM-4 Carbapenemase-producing Enterobacteriaceae, as confirmed by the PHLSB.

 

His family contacts are asymptomatic. The CHP's investigation is under way.

 

This is the 18th detected case of NDM Carbapenemase-producing Enterobacteriaceae in Hong Kong and is the first NDM-4 case reported to the CHP.

 

"NDM-4 is a variant of NDM found in India," a CHP spokesperson said.

(Continue . . . )

 

Like with MRSA, carriage of NDM  bacteria does not necessarily mean infection, but asymptomatic carriers can still spread it to contacts and to the environment.

 

The rise of antibiotic resistance - including these emerging NDM enzymes - 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.

 

For more on the importance of proper antibiotic stewardship, you may wish to revisit these earlier blogs.

 

Chan: World Faces A `Post-Antibiotic Era’

Get Smart About Antibiotics Week

IDSA: Educational Guidelines Lower Antibiotic Use

 

And 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, part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.

EID Journal: Extensively Drug Resistant NDM Bacteria In The Environment – Dhaka, 2012

E. coli – Photo Credit CDC

 

# 9994

 

It’s been nearly 5 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 (New Delhi metallo-β-lactamase) enzyme that can make many types of bacteria resistant to a wide spectrum of antibiotics - including 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.

 

Complicating matters, 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) in a shared environment. 

In 2011 (see Lancet Study: NDM-1 In New Delhi Water Supply), Timothy Walsh, Janis Weeks, David M Livermore, and Mark A Toleman  published a study that looked for – and found – bacteria carrying the NDM-1 enzyme in New Delhi's drinking 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. Like with MRSA, carriage of NDM  bacteria does not necessarily mean infection, and even asymptomatic carriers can still spread it to contacts and to the environment.

 

Since then, scattered variants of NDM-1 have begun to emerge (see First Imported Case Of NDM-4 Reported In Hong Kong) around the globe, often in travelers recently returned from the Indian Subcontinent (see VOA News  report  Concerns Mount Over India's Role In Incubating Drug-Resistant Bacteria).

 

India’s response to all of this negative publicity was initially angry denial, but in 2014 – bowing to immense international pressure – India introduced new regulations designed to halt the unregulated sale of more than 3 dozen cheap and powerful (Schedule H1) antibiotics.

 

Recent media reports (see 515 chemists lose licences in Pune div) suggest less than full compliance, so it is difficult to know how much of an impact these laws are having.

 

Last year, in EID Journal: Acquisition of Drug Resistant Genes Through International Travel, we looked at a study from the Netherlands tested that 122 healthy travelers both before and after making an international trip for evidence that they carried one of (several) antimicrobial resistance-inducing genes.

 

They found a high rate of resistance genes in the commensal gut bacteria of returning travelers – particularly those visiting Southeast Asia and the Indian subcontinent .

 

All of which serves a prelude to a new Dispatch in the EID Journal  – again from Dr. Toleman et al.  - that looked for, and found, NDM encoding bacteria prevalent in the Dhaka’s environment.  They also found evidence - that while rife today - this carbapenemase is a relatively recent arrival to Bangladesh.

 

I’ve only excerpted the abstract and conclusions, so follow the link to read this report in it its entirety.

 

Dispatch

Extensively Drug-Resistant New Delhi Metallo-β-Lactamase–Encoding Bacteria in the Environment, Dhaka, Bangladesh, 2012

Mark A. Toleman , Joachim J. Bugert, and Syed A. Nizam

Abstract

Carriage of the New Delhi metallo-β-lactamase variant 1 (NDM-1) enables drug resistance to move between communities and hospitals. In Bangladesh, we found the bla_NDM-1 gene in 62% of environmental waters and in fermentative and nonfermentative gram-negative bacteria. Escherichia coli sequence type (ST) 101 was most commonly found, reflecting a common global relationship between ST101 and NDM-1.

<SNIP>

Conclusions

Our findings indicate that NDM-1 is widespread in the Dhaka environment. We detected 241 NDM-1–encoding bacterial isolates; they were found in all 7 sampled regions and at 36 (62%) of the 58 sampling sites. This high level of environmental bla_NDM-1 contamination is of concern, especially because drinking water in Bangladesh usually carries high levels of sewage-derived bacteria (11). It is therefore likely that bla_NDM-1 carriage rates will rise rapidly. Future environmental studies could provide indicators of epidemics of emerging resistant bacteria before they are realized in hospitals.

Despite the widespread presence of NDM-1 in Dhaka, it appears that this carbapenemase has recently emerged in the Bangladesh environment. Studies in northern Bangladesh did not find NDM-1 in wild ducks and poultry in 2009 (9) or in crow and gull feces in 2010 (10). Similarly, NDM-1 was not detected in drinking water in Dhaka during 2008–2009 (11) even though all samples had high levels of fecal and bla_CTX-M-15 contamination. Furthermore, a study of 1,879 clinical E. coli and Shigella spp. isolates collected during 2009–2010 in Bangladesh did not detect bla_NDM-1 (12). The first known clinical isolates date from 2008 (12), and the first evidence of human gut carriage of bla_NDM-1 was found in samples collected in Dhaka (13) a month before our study.

Because E. coli is the leading cause of human urinary tract infections, bloodstream infections, and neonatal meningitis, the ability of NDM-1 to give this bacterium clinical resistance to carbapenems is of concern (14). E. coli is also universally carried in the human gut. Therefore, we focused on this species because it is likely to be the greatest threat to human health. E. coli encoding NDM-1 were found in 3 of the 7 sampled regions, and genotyping showed they belonged to only 3 STs: ST648, ST101, and ST405. These same 3 E. coli genotypes are responsible for 80% of clinical NDM-1–encoding E. coli isolates in the United Kingdom (15). Furthermore, ST101 is the most common E. coli genotype in the Bangladesh environment (10.3% prevalence) and in clinical isolates from the United Kingdom (50%). Results of a literature search for NDM-1–encoding E. coli belonging to ST101 showed that this genotype has been detected in 15 nations (Figure 2). Thus, E. coli ST101 appears to be a successful global genotype that is often associated with NDM-1. This association with a single global genotype is analogous to the association between E. coli ST131 and the cephalosporinase CTX-M-15. Because of the critical nature of extensively drug-resistant bacteria, we are investigating the underlying factors responsible for the success of these particular antimicrobial drug–resistant strains

 

While still relatively rare – at least in the United States and Europe – this ever expanding rogues gallery of new, multi-drug resistant organisms continues to gain traction around the world, threatening an early demise for much of our current antibiotic arsenal. 

 

In early 2012 World Health Director-General Margaret Chan expressed a dire warning about our dwindling antibiotic arsenal (see Chan: World Faces A `Post-Antibiotic Era’). A year later CDC Director Thomas Frieden called it a `nightmare bacteria’ during the release of a major US report on the threat (see MMWR Vital Signs: Carbapenem-Resistant Enterobacteriaceae (CRE)).

 

For more on the growing threat of antibiotic resistant bacteria, you may wish to revisit:

 

AAP/CDC: New Guidance On For Antibiotics For Children

The Lancet: Antibiotic Resistance - The Need For Global Solutions

UK CMO: Antimicrobial Resistance Poses `Catastrophic Threat’

Eurosurveillance: NDM-producing E. coli Isolated From Recreational Waters, Sewage & Clinical Specimen - Ireland

#12,385



It was just six and a half years ago that  Professor Timothy Walsh et al. published their study Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study describing the NDM-1 enzyme.

The NDM (New Delhi metallo-ß-lactamase) gene – conveys resistance to the Carbapenem class of antibiotics, which are often used as the drug of last resort for treating difficult bacterial infections, including Escherichia coli (E. coli) and Klebsiella pneumoniae.

Since then we’ve seen a steady stream of reports of NDM-1 (and variants, like NDM-2, NDM-4, NDM-5, etc) turn up around the globe.  Worse, the NDM gene can be carried by plasmids - tiny pieces of mobile DNA - that can be shared between different types of bacteria.

Since it requires physical contact between two different types of bacteria for plasmids to make this transfer, man-made environments where many types of bacteria are thrown together -  such as sewage treatment plants and contaminated water supplies -  are viewed as potential breeding sites for resistant bacteria.

• In late 2013, we looked at a study (see NDM-1 Bacteria Survive & Thrive In Two Chinese Wastewater Treatment Plants) that found the (New Delhi metallo-β-lactamase) enzyme not only survived processing in two Chinese WWTPs, they actually were found to multiply in that environment.
• A year earlier, in Study: MRSA In Waste Water Treatment Plants  (WWTPs) we learned that MRSA can survive the waste water treatment process, and potentially could end up redistributed via reclaimed irrigation water.
• And in 2011, in Study: Adaptation Of Plasmids To New Bacterial Species, we looked at the ability of plasmids – tiny snippets of portable DNA that can carry resistance enzymes – to transfer horizontally to other strains of bacteria.

While environmental samples in India and China had originally turned up with NDM producing bacteria, over the past few years these resistant bacteria have increasingly been detected around the globe, including in Europe.

A 2014 study – conducted by the UK’s University of Warwick – made huge headlines (see Drug-resistant bacteria: Sewage-treatment plants described as giant 'mixing vessels' after scientists discover mutated microbes in British river). 

We looked at the actual report in WWTPs As `Mixing Vessels’ For Resistant Bacteria.

 
Today the ECDC's Eurosurveillance Journal has a report of environmental contamination of a public beach in Ireland with NDM-producing E. coli bacteria - apparently shed by a nearby waste water treatment plant. 

I've only posted some excerpts, so follow the link to read the report in its entirety.

Eurosurveillance, Volume 22, Issue 15, 13 April 2017
Rapid communication

Indistinguishable NDM-producing Escherichia coli isolated from recreational waters, sewage, and a clinical specimen in Ireland, 2016 to 2017

BM Mahon 1 , C Brehony 1 , E McGrath 2 3 , J Killeen 1 , M Cormican 1 2 3 , P Hickey 4 , S Keane 4 , B Hanahoe 3 , A Dolan 5 , D Morris 1


Euro Surveill. 2017;22(15):pii=30513. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.15.30513

Received:00 March 2017; Accepted:12 April 2017

In this study, New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae were identified in Irish recreational waters and sewage. Indistinguishable NDM-producing Escherichia coli by pulsed-field gel electrophoresis were isolated from sewage, a fresh water stream and a human source. NDM-producing Klebsiella pneumoniae isolated from sewage and seawater in the same area were closely related to each other and to a human isolate. This raises concerns regarding the potential for sewage discharges to contribute to the spread of carbapenemase-producing Enterobacteriaceae.

We report the finding of New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae in fresh water and seawater samples collected at two beaches located near an untreated human sewage ocean discharge. Isolates of NDM-producing Escherichia coli derived from the sewage collection system, the sewage storage tank and the outflow were 100% identical by pulsed-field gel electrophoresis (PFGE) to those derived from a fresh water stream on one of the beaches, and to a clinical isolate.

         (SNIP)

We consider that contamination of the environment with NDM-producing Enterobacteriaceae from the human sewage outflow is likely to be the source, and that the fresh water streams were contaminated by backwash of sewage onto the beach by tidal currents. The presence of NDM-producing Enterobacteriaceae in the bathing water (seawater) and at a separate bathing site ca 950 m in a direct line indicates the extent of this contamination. It is important to note that by the established regulatory standards, the bathing water quality in the area concerned has been consistently of sufficient quality [18].

Notwithstanding compliance with regulatory standards however, it is reasonable to conclude that those using a beach such as this for recreational purposes might be at least intermittently exposed to NDM-producing Enterobacteriaceae. Although, to date, there is no evidence that NDM-producing Enterobacteriaceae has been acquired as a result of exposure to this beach environment, Leonard et al. have recently reported on the level of risk of exposure to antibiotic resistant bacteria in coastal waters and its relationship to different types of water sports [19].

It appears therefore that there is potential for environmental contamination to contribute to a transition of CPE from largely healthcare-associated organisms, to organisms affecting the general population and the veterinary sector. From a public health perspective, the findings focus attention on the need to accelerate programmes to cease discharge of untreated sewage into the environment. This practice should be unacceptable in the context of discharges in the vicinity of popular bathing and recreation areas where human exposure is highly likely.

         (Continue. . . )



 For a look at some other unintended consequences arising from WWTPs, you may wish to revisit:

AAC: LPAI H7N9 Acquires Antiviral Resistance When Exposed To Environmental Oseltamivir

Pandemics & The Law Of Unintended Consequences

Everything Old Is News Again

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.

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.

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.

MMWR: Denver Hospital Outbreak Of NDM-Producing CRKP

 

CDC Guidance For Control Of CRE

# 6937

 

Today’s MMWR has the details on an outbreak of NDM-Producing CRKP, or Carbapenem-Resistant Klebsiella pneumoniae, at an acute-care hospital in Denver during first 10 months of 2012. Klebsiella pneumoniae is a Gram negative, rod shaped bacterium commonly found in the flora of the human intestinal tract.

 

Most of the time, it resides harmlessly in the intestines.

 

But when K. pneumoniae moves beyond the intestinal tract – particularly in people with weakened immune systems – it can cause cause severe pneumonia, urinary tract infections (UTI), septicemia, and soft tissue infections.

 

Complicating matters, over the past decade doctors have seen the emergence of antibiotic resistant forms of K. pneumoniae – known as CRKP or  KPC (K. pneumoniae carbapenemase). 

 

Bacteria resistant to the Carbapenem class of antibiotics (a class that includes imipenem, meropenem, doripenem, and ertapenem) – are called carbapenemases –  are of particular concern since Carbapenems are often the drug of last resort for treating difficult bacterial infections.

 

The reference to NDM-Producing is the detection of an emerging enzyme – called NDM or New Delhi metallo-beta-lactamase – that confers resistance to a number of different bacteria. The NDM enzyme was first detected in Sweden in 2008 from a patient with travel history to India.

 

Two and a half years ago 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.

 

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

 

Since the discovery of NMD-1 5 years ago, scattered variants have begun to emerge; NDM-2, NDM-4, and NDM-5.

 

Up until now, the primary risk for contracting an NMD producing bacterial infection has been receiving medical care in those regions of the globe where these resistant strains have become endemic – notably South Asia.

 

But increasingly, these resistant organisms are making their way around the globe (presumably spread by asymptomatic carriers), and as the following report indicates, how it gets into a medical facility isn’t always known.

 

But once introduced, it can be very difficult to contain.

 

 

Notes from the Field: Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase — Denver, Colorado, 2012

Weekly

February 15, 2013 / 62(06);108-108

On August 16, 2012, the Colorado Department of Public Health and Environment was notified of two patients at an acute-care hospital in Denver with carbapenem-resistant Enterobacteriaceae (CRE), specifically Klebsiella pneumoniae (CRKP), isolated from respiratory specimens during July–August. Both isolates produced New Delhi metallo-beta-lactamase (NDM). A review of microbiology records identified a third patient with NDM-producing CRKP isolated from a respiratory specimen, admitted in May. Active surveillance cultures in September identified an additional five patients colonized with NDM-producing CRKP. An investigation was launched by the hospital and the Colorado Department of Public Health and Environment to guide infection control measures and limit transmission.

 

A case was defined as NDM-producing CRE isolated from clinical or active surveillance cultures collected from a patient while hospitalized during January 1–October 30, 2012. Medical records were reviewed for clinical and epidemiologic characteristics. Relatedness of isolates was evaluated by pulsed-field gel electrophoresis (PFGE).

 

The eight patients were aged 23–75 years and had been hospitalized at one or more of 11 different units in the hospital for a median of 18 days (range: 12–83 days) before CRKP identification. Three were treated for CRKP infection, and five were found to be asymptomatically colonized; none died. Initial isolates were resistant to all antimicrobials except tigecycline, to which all were susceptible. Colistin minimum inhibitory concentrations for six isolates were low (≤2 µg/mL), suggesting this agent might be a treatment option. All isolates were highly related by PFGE. Epidemiologic tracing to determine temporal overlap of patients on units in the hospital indicated multiple transmission events had occurred, and three units were likely transmission sites. Acquisition of NDM-producing CRE by some patients was not explained by direct overlap and suggested that undetected, asymptomatically colonized patients were involved in some transmission routes. How NDM-producing CRE was introduced to the facility is unclear.

 

NDM, a carbapenemase enzyme first described in 2009 in a patient who had received medical care in India (1), has since been detected and reported worldwide (2). In the United States, before this outbreak, only 16 isolates in clusters with two or fewer cases had been identified since 2009; 14 isolates were from patients who had received medical care in endemic (South Asian) regions. The cases described here represent the largest U.S. outbreak of NDM-producing CRE to date, highlighting the risk for spread of these organisms among persons receiving medical care inside the United States. Evidence that undetected, asymptomatically colonized patients likely contributed to the size of the outbreak highlights the importance of timely active surveillance cultures when CRE is identified to direct infection control measures and limit further transmission (3).

Reported by

Larissa Pisney, MD, Michelle Barron MD, Div of Infectious Diseases, Univ of Colorado; Sarah Jackson Janelle, MPH, Wendy Bamberg, MD, Colorado Dept of Public Health and Environment. Duncan MacCannell, PhD, Antimicrobial Resistance and Characterization Laboratory; Alexander Kallen, MD, Carolyn Gould, MD, Brandi Limbago, PhD, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases; Erin Epson, MD, Joyanna Wendt, MD, EIS officers, CDC. Corresponding contributor: Erin Epson, erin.epson@state.co.us, 303-692-2745.

 

 

While some of the warnings issued over the past couple of years regarding the growth and spread of antibiotic resistant organisms may have seemed a bit hyperbolic to the general public, I firmly believe that modern medicine will face no greater challenge over the next couple of decades.

 

Few, if any, new classes of antibiotics are in the pipeline, and with each passing day bacteria get better at evading our dwindling antibiotic arsenal.

 

The rise of antibiotic resistance - including these emerging NDM enzymes - 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.

 

For more on the importance of proper antibiotic stewardship, you may wish to revisit these earlier blogs.

 

Chan: World Faces A `Post-Antibiotic Era’

Get Smart About Antibiotics Week

IDSA: Educational Guidelines Lower Antibiotic Use

 

And 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.

Superbug (MRSA) Book

 

Meanwhile, Maryn’s SUPERBUG Blog, continues to provide the best day-to-day coverage of these issues.

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

MMWR: NDM-1 Transmission In Rhode Island

 

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

 

 

# 6397

 

From the today’s MMWR , we’ve a report on the importation and likely nosocomial transmission of a CRE (carabapenem-resistant Enterobacteriaceae) infection containing NDM-1.

 

NMD-1, or New Delhi metallo-ß-lactamase-1 – is an enzyme which confers broad antibiotic resistance to various types of bacteria. Even more troubling, it rides on a plasmid (a snippet of portable DNA) that can be shared by different types of bacteria.

 

The good news is that NDM-1 cases in the United States are still rare enough that they merit extensive reportage in the CDC’s MMWR. The bad news is, they continue to spread around the globe and our treatment options against them are extremely limited.

 

A few excerpts from today’s MMWR report follow (slightly reparagraphed for readability). 

 

 

Carbapenem-Resistant Enterobacteriaceae Containing New Delhi Metallo-Beta-Lactamase in Two Patients — Rhode Island, March 2012

 

June 22, 2012 / 61(24);446-448

U.S. and international efforts to control carabapenem-resistant Enterobacteriaceae (CRE) are critical to protect public health. Clinicians caring for patients infected with such organisms have few, if any, therapeutic options available. CRE containing New Delhi metallo-beta-lactamase (NDM), first reported in a patient who had been hospitalized in New Delhi, India, in 2007 (1), are of particular concern because these enzymes usually are encoded on plasmids that harbor multiple resistance determinants and are transmitted easily to other Enterobacteriaceae and other genera of bacteria (2).

 

A urine specimen collected on March 4, 2012, from a patient who recently had been hospitalized in Viet Nam, but who was receiving care at a hospital in Rhode Island, was found to have a Klebsiella pneumoniae isolate containing NDM.

 

The isolate was susceptible only to tigecycline, colistin, and polymyxin B. Point-prevalence surveys of epidemiologically linked patients revealed transmission to a second patient on the hematology/oncology unit.

 

These two cases bring to 13 the number of cases of NDM reported in the United States. After contact precautions were reinforced and environmental cleaning was implemented, no further cases were identified.

 

<SNIP Lengthy Narrative On Patients, Lab Tests, and Isolation Methods>

 

Reported by

Erica E. Hardy, MD, Leonard A. Mermel, DO, Dept of Medicine, Kimberle C. Chapin, MD, Dept of Pathology, Warren Alpert Medical School of Brown Univ; Cindy Vanner, Rhode Island Dept of Health. Ekta Gupta, MD, Dept of Medicine, Boston Univ School of Medicine, Massachusetts. Corresponding contributor: Leonard A. Mermel, lmermel@lifespan.org, 401-444-2608.

Editorial Note

Since the first report in 2009, cases involving NDM-producing Enterobacteriaceae have been reported in every continent except South America and Antarctica (7). Among 29 cases in the United Kingdom, at least 17 involved patients who had traveled to India or Pakistan, among whom 14 had been hospitalized in one of those countries (8).

 

Although medical care in the Indian subcontinent was associated with many early reports, recent cases have been described involving persons who traveled to endemic regions* but were not hospitalized (7). The plasmid-carrying NDM is highly transmissible to other bacteria, and bacteria carrying NDM can colonize the gastrointestinal systems of humans for prolonged periods and can spread through contamination of water sources and environmental surfaces (7).

 

Not surprisingly, nosocomial spread also has been documented outside of the Indian subcontinent. Of 77 cases of infection or colonization with CRE containing NDM in Europe, 13 might have been hospital-acquired in Europe (9). Spread of NDM in other parts of Asia also has been reported, including four patients in South Korea without travel history (10), similar to recent reports elsewhere (7).

 

(Continue . . . )

 

 

In summary, the report offers the following:

 

What is already known on this topic?

New Delhi metallo-beta-lactamase (NDM)–producing Klebsiella pneumoniae are resistant to extended-spectrum antimicrobials, including carbapenems. The resistance mechanism is highly transmissible and its presence substantially limits treatment options. NDM-producing Enterobacteriaceae have been identified in the United States, primarily among patients with exposure to health care in endemic countries.

 

What is added by this report?

An NDM-producing organism was isolated from a patient being treated in the United States after having been hospitalized in Vietnam. Implementation of CDC-recommended carbapenem-resistant Enterobacteriaceae (CRE) control practices, including surveillance cultures of epidemiologically linked contacts, identified likely transmission to one other patient on the same ward of the U.S. hospital. Additional control measures were applied and additional surveillance and clinical cultures have not identified further transmission.

 

What are the implications for public health practice?

An aggressive approach to control of CRE, including highly transmissible carbapenemase-producing organisms, is essential to slow the spread of these organisms in the United States. In an outbreak, use of surveillance cultures to identify asymptomatic transmission potentially is an important part of these efforts.

 

 

I  wrote about this emerging public health threat less than a week ago, in NDM-1: A Matter Of Import. The following link will provide a list of some of my past blogs on the NDM-1 enzyme.

 

Without a doubt  the `go to’ blogger on all things antibiotic resistant is Maryn McKenna, author of Superbug: The Fatal Menace of MRSA. If you aren’t a regular visitor to her Superbug Blog, you should be.

 

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 this one add to the growing concern that someday, that fear may become a reality.

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.

Study: NDM-1 Bacteria Survive & Thrive In Two Chinese Wastewater Treatment Plants

Photo Credit USGS – Wastewater: The Primary Treatment Process

1. Screening 2. Pumping 3. Aerating 4. Removing sludge 5. Removing Scum 6. killing bacteria

 

# 8079

 

It’s been just over 3 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 (New Delhi metallo-β-lactamase) enzyme that can make many types of bacteria resistant to a wide spectrum of antibiotics.

 

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 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.

Six months after the first Lancet article - in April, 2011 - the same researchers published another study that found the NDM-1 enzyme in 4% of New Delhi’s sampled drinking water sources, and 30 per cent of the sewage tested. Most alarmingly, the researchers also identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

 

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

 

Last year, in Study: MRSA In Waste Water Treatment Plants  (WWTPs) we learned that MRSA (methicillin-resistant Staphylococcus aureus) can survive the waste water treatment process, and potentially could end up redistributed via reclaimed irrigation water.

Today, we’ve a new study conducted by scientists from Rice, Nankai and Tianjin universities that found NDM-1 bacteria not only survived processing in two Chinese WWTPs, they actually were found to multiply in that environment.

First a link to the study which appears in Environmental Science & Technology , then some excerpts from a press release from Rice University.

 

Proliferation of Multidrug-Resistant New Delhi Metallo-β-lactamase Genes in Municipal Wastewater Treatment Plants in Northern China

Yi Luo †, Fengxia Yang †‡, Jacques Mathieu §, Daqing Mao *‡, Qing Wang †, and P. J. J. Alvarez *§

ABSTRACT

The New Delhi metallo-β-lactamase (NDM-1) increases bacterial resistance to a broad range of antibiotics, and bacteria that produce it can cause infections that are very difficult to treat, thus posing great risks to human health. This paper addresses the occurrence of NDM-1 genes through different processes in wastewater treatment plants (WWTPs). NDM-1 genes prevailed through several treatment units (including disinfection by chlorination) in two WWTPs in northern China. Significant NDM-1 gene levels were present in the effluent discharged from both WWTPs (from 1316 ± 232 to 1431 ± 247 copies/mL, representing from 4.4 to 93.2%, respectively, of influent levels). NDM-1 genes were present at much higher concentrations in dewatered waste sludge that is applied to soils [(4.06 ± 0.98) × 10⁷ to (6.21 ± 2.23) × 10⁷ copies/g of dry weight], raising the possibility of propagation to indigenous bacteria. This concern was validated by a conjugation experiment with Haihe River sediment not harboring NDM-1 genes at detectable levels, where an NDM-1-positive Achromobacter sp. isolated from a WWTP transferred the NDM-1 gene to an indigenous Comamonas sp. The discharge of NDM-1 genes in the effluent and dewatered waste sludge from WWTPs (even at rates higher than influent values) underscores the need to better understand and mitigate their proliferation and propagation from WWTPs.

(Continue . . .)

 

The entire PDF is available at the link above.  Here are a few excerpts from the press release,after which I’ll be back with a little more:

 

Superbugs’ found breeding in sewage plants

Mike Williams

– December 16, 2013Posted in: News Releases

 

‘Superbugs’ found breeding in sewage plants

Rice U. study: Two wastewater treatment plants in China fail to kill antibiotic-resistant bacteria 

HOUSTON – (Dec. 16, 2013) – Tests at two wastewater treatment plants in northern China revealed antibiotic-resistant bacteria were not only escaping purification but also breeding and spreading their dangerous cargo.

 

Joint research by scientists from Rice, Nankai and Tianjin universities found “superbugs” carrying New Delhi Metallo-beta-lactamase (NDM-1), a multidrug-resistant gene first identified in India in 2010, in wastewater disinfected by chlorination. They found significant levels of NDM-1 in the effluent released to the environment and even higher levels in dewatered sludge applied to soils.

 

The study, led by Rice University environmental engineer Pedro Alvarez, appeared this month in the American Chemical Society journal Environmental Science and Technology Letters.

 

“It’s scary,” Alvarez said. “There’s no antibiotic that can kill them. We only realized they exist just a little while ago when a Swedish man got infected in India, in New Delhi. Now, people are beginning to realize that more and more tourists trying to go to the upper waters of the Ganges River are getting these infections that cannot be treated.

 

“We often think about sewage treatment plants as a way to protect us, to get rid of all of these disease-causing constituents in wastewater. But it turns out these microbes are growing. They’re eating sewage, so they proliferate. In one wastewater treatment plant, we had four to five of these superbugs coming out for every one that came in.”

(Continue . . . )

Concerns over WWTPs extend even beyond resistant bacteria, as they are also called upon to deal with drugs and chemicals either dumped into the system, or excreted from humans in their waste.  In recent years we’ve seen a number of reports on detectable levels of drugs in rivers and streams that passed relatively intact through treatment facilities.

 

More than six  years ago, the subject of what happens to Tamiflu once it is excreted by the human body first graced these pages.The blog was called The Law of Unintended Consequences, and it looked a study conducted at the Centre for Ecology and Hydrology in Oxford, England.

 

Their findings were released in the January 2007 issue of Environmental Health Perspectives (EHP) in a report entitled, Potential Risks Associated with the Proposed Widespread Use of Tamiflu, that illustrated what might happen if millions of people simultaneously began taking Tamiflu and releasing it into our environment.

 

The upshot of the the study was that scientists believed enough of the metabolite OC (oseltamivir carboxylate) would be present in some rivers and streams, after sewage plant processing, to present a genuine risk to the environment.

 

The concern being that enough Tamiflu might persist after wastewater treatment and release to rivers and streams that it might speed the development of resistant influenza viruses in waterfowl.

 

Fast forward to October of 2009 and we saw another report (see Everything Old Is News Again), based on studies done the previous year in Kyoto, Japan – that showed elevated levels of the OC Metabolite in wastewater discharge.

 

More recently, investigators looking at the levels chemicals in rivers downstream from a pharmaceutical manufacturing hub in India, found staggering amounts of antibiotics along with signs of resistant bacteria.

 

That story was  well covered by Maryn McKenna on her Superbug Blog (see Drug residues and drug resistance in water: Not good).

 

Since  Wastewater Treatment Plants depend upon microbial activity in order to breakdown or `digest’ sewage, large quantities of antibiotics in the sewage could inhibit microbial activity, resulting in the failure of WWTPs and the discharge of under-treated wastewater into the environment. 

 

While I’m sure most of us would like to simply `flush and forget it’, the truth is wastewater infrastructures around the world are continually called upon to deal with new, and sometimes difficult challenges, and in many places the technology simply isn’t currently up to the task. 

 

Another good reason to dispose of prescription drugs properly, and not just flush them down the drain.