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’

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.

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.

India: Still Looking For A Policy On Antibiotics

 

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

# 6502

 

Although the antibiotic resistance enzyme now known as NDM-1 (New Delhi metallo-ß-lactamase-1) was first detected in a patient in Sweden (albeit with Indian origins) four years ago, it didn’t capture much attention until the publication of an eye-opening research paper in The Lancet in August of 2010.

 

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

Dr David Livermore, Prof Timothy Walsh, et al.

doi:10.1016/S1473-3099(10)70143-2

Published Online: 11 August 2010

 

This study linked the recent importation of a handful of NDM-1 infections into the UK, US, and other countries  to `medical tourism’ on the Indian Sub-continent (see NDM-1: A New Acronym To Memorize).

 

NDM-1 is an 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 has long been linked to the overuse and misuse of antibiotics.

 

Citing a lack of doctors and low family incomes, the Indian government allows the unfettered sale of antibiotics to the public without a doctor’s prescription.

 

Indian officials swiftly reacted to the Lancet paper, but rather than taking immediate action against a growing public health menace, they took umbrage instead.

 

They condemned of the use of `New Delhi’ in the naming of this resistance gene and called the paper a `conspiracy theory’.  They 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 India’s ire has long used the pathogen’s place of discovery or emergence. India was certainly not singled out.

 

After intense pressure from the International community and scathing editorializing in Indian newspapers, the Indian Health Ministry announced in October 2010 that they would impose new restrictions on the sale of 90 antibiotics that were currently sold over-the-counter.

 

But that plan was eventually abandoned. Two years later, the sale of antibiotics remains rampant and unregulated in India.

 

This article appeared last week in The Hindu.

 

 

Wanted: a policy on antibiotics

R. Sujatha

It needed a scare like NDM-1 for the country to wake up to a policy to regulate antibiotics. But after announcing with much fanfare that a policy would be in place, the government withdrew the decision. We have arrived at a crossroads and there is no solution to the crisis yet.

(Continue . . .)

 

 

The story goes on to say that next week doctors from around the country will meet in Chennai to try to come up some kind of  `road map’ for the government to use to implement an antibiotic policy. 

 

Whether they will succeed, and whether the government will follow through, remains to be seen.

 

Meanwhile, as policy makers dither, the NDM-1 enzyme continues its evolution and spread.

 

Six months after the first Lancet article in April, 2011, the same researchers published a 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.

 

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 most alarmingly, 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 denial (see Hopefully, It’s Just A Stage They Are Going Through). 

 

Last fall, despite ongoing denials from the Indian government, we saw a number of stories that helped to corroborate 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."

 

Another related article, that appeared in the International Business Times, quotes Former Indian Council of Medical Research chief and chairman N.K. Ganguly as 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

 

 

Last March (see Chan: World Faces A `Post-Antibiotic Era’), World Health Organization Director-General Margaret Chan – delivering the  keynote address to the Conference on Combating Antimicrobial Resistance in Copenhagen, Denmark - painted a bleak picture of the future of antibiotic availability if action is not taken.

 

The D-G’s entire remarks may be viewed on the WHO’s website at Antimicrobial resistance in the European Union and the world, but I’ve excerpted a few choice statements below, after which you’ll find a link to the World Health Organization’s latest publication on antibiotic resistance.

 

Excerpts from D-G Chan’s March 14th, 2012 speech.

 

Antimicrobial resistance is on the rise in Europe, and elsewhere in the world. We are losing our first-line antimicrobials. Replacement treatments are more costly, more toxic, need much longer durations of treatment, and may require treatment in intensive care units.

 

<SNIP>

 

If current trends continue unabated, the future is easy to predict. Some experts say we are moving back to the pre-antibiotic era. No. This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry, especially for gram-negative bacteria. The cupboard is nearly bare.

 

<SNIP>

 

A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill.

The evolving threat of antimicrobial resistance - Options for action

Authors:
World Health Organization

 

 

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 linked to their lax controls on the sale and use of antibiotics.

 

Short of seeing a hyper-virulent pandemic someday, I can think of no public health crisis with a bigger potential impact than the growth of antibiotic resistant pathogens.

 

While I dabble in the subject from time to time, 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.

 

If and when the Indian government imposes meaningful restrictions on the sale of antibiotics, I’ll report it. 

 

One just hopes that happens before the point becomes moot.

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.

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.

NDM-1: A Matter Of Import

 

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

 

# 6390

 

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. on the emergence and growing prevalence a new enzyme – dubbed NDM-1 (New Delhi metallo-ß-lactamase-1) - on the Indian sub-continent 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.

 

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).

 

While the numbers were small, the authors identified a handful of patients in the UK who had recently travelled to the Indian Subcontinent and who returned with this resistant bacteria.

 

The reaction from officials out of India was both swift and disappointing. Rather than taking immediate 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.

 

Under mounting pressure from the International community and editorializing in Indian newspapers, the Indian Health Ministry announced in October 2010 that they would impose new restrictions on the sale of 90 currently over-the-counter antibiotics.

 

But as the Deccan Chronicle reported as recently as last month, in an article called Medical body demands ban on 33 drugs in India (published May 20, 2012), little progress has been made:

 

Sale of antibiotics without prescription is rampant

Despite the government regulations restricting the sale of drugs without a prescription, medical stores continue to do so in the absence of active government monitoring. In particular, antibiotics can be obtained at medical stores just by naming them. Doctors say such an unchecked sale of antibiotics is harmful from the public's perspective.

 

Even though the policy framework of the Directorate General of Health Services seeks to regulate the unauthorised sale of antibiotics, the practice is rampant.

 

 

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.

 

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

 

 

Today the VOA (Voice of America) carries a report on the growing concerns over the spread of Drug Resistant bacteria across India. A problem exacerbated not only by the unregulated sale of antibiotics over the counter, but also by a lack of waste treatment facilities in that country of more than 1 billion people.

 

Concerns Mount Over India's Role In Incubating Drug-Resistant Bacteria

Kurt Achin

May 16, 2012

Medical research is once again pointing to India as a dangerous crucible of bacterial strains that resist many forms of antibiotic treatment. Cheap, under-regulated antibiotics and a severe shortfall of sanitation infrastructure fuel the problem.

 

<SNIP>

 

Unsanitary conditions in India are blamed for creating an environment for superbugs - both in emerging megacities, and in rural locations where toilet infrastructure is nearly nonexistent.

Nitya Jacob, head of water issues at New Delhi's Center for Science and Environment, co-authored a recent study called “Excreta Matters.”

"India has a capacity to treat only about a fifth of its sewage and I think about 40 percent of that capacity is concentrated in just two cities of Delhi and Bombay," said Jacob.

Superbug researcher Kumarasamy says the Indian government needs to act urgently to prevent the spread of drug-resistant diseases.

(Continue . . .)

 

More detail on the Excreta Matters study, referenced above, can be found on the Centre For Science and Environment website.

 

 

Meanwhile, as governments dither and regulations go unenforced - superbugs like NDM-1, acinetobacter, and a myriad of carbapenamases including: IMP, VIM, OXA, CMY, and most notably KPC (K. pneumoniae carbapenemase) - continue their pernicious spread around the world.

 

A story out of Edmonton, Canada last week illustrates this point, showing just how easily superbugs can be imported, and then spread:

 

Health officials admit superbug lead to death of patient at Royal Alex

Updated: Wed Jun. 06 2012 19:18:56
Julia Parrish, ctvedmonton.ca

Weeks after two types of drug resistant bacteria were brought into Edmonton by a woman who had surgery overseas, health officials have confirmed those `superbugs' lead to the death of another patient at the Royal Alexandra Hospital.

(Continue . . . )

 

 

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, the ECDC, and the CDC all consider the spread of antibiotic resistant organisms to be an extremely urgent public health concern.

 

For more on these issues, you may wish to revisit:

 

Carbapenemases Rising

Chan: World Faces A `Post-Antibiotic Era’

WHO: The Evolving Threat Of Antimicrobial Resistance

 

 

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.

The Passing Parade Of 2011 – Pt. 2

 

 

 

# 6036

 

Over the past year I’ve posted more than 900 blogs, dozens of which looked at some of the latest research into influenza and other emerging infectious diseases.

 

Since these studies oft times make an initial splash only to get lost in the passing parade of new reports, today I’ve some brief summaries (with links back to the original blogs) on some of the research of 2011 I believe is deserving of a second look.

 

This is the second such roundup, the first one may be accessed at this link.

 

 

Last April in Lancet Study: NDM-1 In New Delhi Water Supply, we saw a report 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.

 

We’ve a press release on this study, issued by Cardiff University, that gives the highlights of the research, 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.

 

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)70059-7

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

 

Again in April, we saw research seeking to answer the question over why there was such a wide variance in death rates around the world with the 1918 Spanish influenza. 

 

In 2006, in a Lancet journal (doi:10.1016/S0140- 6736(06) 69895-4) article cited as much as a 30-fold difference in mortality rates around the world:

 

Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918—20 pandemic: a quantitative analysis

Christopher JL Murray , Alan D Lopez , Brian Chin , Dennis Feehan , Kenneth H Hill

Excess mortality ranged from 0·2% in Denmark to 4·4% in India. Since there was some under-registration of mortality in India, total pandemic mortality could have been even higher.

 

 

This wide disparity in mortality rates – much of it based on anecdotal accounts – has long intrigued researchers.  This new study from the Norwegian Institute of Public Health that attempts to answer some of these questions.

 

What they found was that the mortality rate varied nearly 100 fold between remote, rural regions and urban populations, and that in the more remote areas, older persons were just as susceptible to the virus as those who were younger.

 

This study appears in the Journal Epidemics.

Geography May Explain Adult Mortality from the 1918–20 Influenza Pandemic

Original Research Article
Pages 46-60
Svenn-Erik Mamelund

 

The theory that a similar H1 virus circulated prior to 1890 – and that provided some immunity to those over the age of 30 – is bolstered by this study.

 

 

Given the current flap over the H5N1 experiments conducted by Ron Fouchier in the Netherlands and Yoshihiro Kawaoka  at the University of Wisconsin (see The Biosecurity Debate On H5N1 Research) the next two studies deserve a second look as well.

 

 

Simplified Illustration of a Serial Passage Experiment. 

 

In H5N1: A Rite Of Passage we looked at how serial passage studies are conducted, and at one in particular that appeared in the Journal of Animal and Veterinary Advances that looked at increases in pathogenicity (in mice) of two H5N1 viruses after six serial passages in quail.

 

The study is called:

 

The Pathogenicity Variation of Two Quail-Origin H5N1 HPAV to BALB/c Mice after Six Passages in Quail

Hailiang Sun, Peirong Jiao, Yuqiang Cheng, Runyu Yuan, Pengfei Cui, Liming Jin, Chaoan Xin and Ming Liao

 

Another study, profiled in PNAS: Reassortment Potential Of Avian H9N2, looked at the reassortment potential of the avian H9N2 virus and H1N1. Research was done using ferrets whose respiratory physiology is considered relatively close to humans.

 

Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1 internal genes for transmission in the ferret model

J. Brian Kimble, Erin Sorrell,  Hongxia Shao,  Philip L. Martin, and Daniel Roberto Perez

 

(Excerpt from the abstract)

Four reassortant viruses were generated, with three of them showing efficient respiratory droplet transmission. Differences in replication efficiency were observed for these viruses; however, the results clearly indicate that H9N2 avian influenza viruses and pH1N1 viruses, both of which have occasionally infected pigs, have the potential to reassort and generate novel viruses with respiratory transmission potential in mammals.

 

 

The entire study is available online, and open access.

 

 

And in Study: Prior Antibiotic Use & MRSA In Children Canadian researchers, examining 13 years worth of data from the UK’s General Practice Research Database (GPRD), came up with what they called  a `robust association’ between a prior history of antibiotic use and rates of CA-MRSA (Community Acquired Methicillin Resistant Staph Aureus) infection in children.

The study appeared Aug. 1st  in the Archives of Pediatrics & Adolescent Medicine.

 

Antibacterial Drugs and the Risk of Community-Associated Methicillin-Resistant Staphylococcus aureus in Children

Verena Schneider-Lindner, MD, MSc; Caroline Quach, MD, MSc; James A Hanley, PhD; Samy Suissa, PhD

Arch Pediatr Adolesc Med. Published online August 1, 2011. doi:10.1001/archpediatrics.2011.143

 

What these researchers found was that while nearly half of children with MRSA in this study had no recent history of antibiotic use, the adjusted relative risk (RR) of developing MRSA was 3.5 times higher among children who had received antibiotic treatment in the previous 30-180 days before infection.

 

And that relative risk increased substantially among children who received more than one course of antibiotics.

 

To find more blogs specific to research you can use the RESEARCH quick link on my sidebar.

 

As news is often slow during the holiday season, over the next couple of weeks I plan to post one or two more retrospectives on the news and research of the year that was.

Referral: McKenna On NDM-1 In India

 

 

# 5903

 

 

Maryn McKenna, author of Superbug: The Fatal Menace of MRSA, has details on the political and scientific wrangling surrounding the recent international conference on antibiotic resistance held last week in New Delhi (see my posts here, and here).

 

Follow the link below to go to Maryn’s Superbug Blog.

 

NDM-1 in India: Drug Resistance, Political Resistance

• By Maryn McKenna
• October 16, 2011  | 
• 10:14 am  | 
•  

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.