Thursday, April 30, 2015

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.



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

Mark A. TolemanComments to Author , Joachim J. Bugert, and Syed A. Nizam


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 blaNDM-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.



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 blaNDM-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 blaNDM-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 blaCTX-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 blaNDM-1 (12). The first known clinical isolates date from 2008 (12), and the first evidence of human gut carriage of blaNDM-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’

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