Gramnegative enterobacteriaceae with resistance to carbapenem conferred by new delhi metallo. Here, we report an outbreak of ndm 1 producing klebsiella pneumoniae infection in a dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated health care centers hccs. Sidjabat h, nimmo gr, walsh tr, binotto e, htin a, hayashi y. The aim of the study was to determine the prevalence of new delhi metallo.
Acquisition of the bla ndm 1 gene on plasmid p271a had been likely the result. Ndm 1 is an enzyme that can hydrolyse and inactivate carbapenems, which are used as a last resort for the treatment of multiresistant bacterial infections. Analysis of the resistome of a multidrugresistant ndm1. Pseudomonas aeruginosa and acinetobacter baumannii are the common causes of nosocomial infections especially among patients with burn injuries. Embelin restores carbapenem efficacy against ndm1positive. In august, 2010 a study was published in lancet infectious diseases identifying the widespread. The ndm 1 enzyme was named after new delhi, the capital city of india, as it was first described by yong et al. Aug 23, 2017 rmsd plot has shown relatively stable backbone trajectories of ndm1 with m75 average 0. Their susceptibility to 18 antibiotics was performed by determining.
Experts offer perspective on ndm1 resistance threat cidrap. Coexistence of mcr1 and ndm1 in clinical escherichia. Molecular analysis confirmed the presence of the bla ndm 1 gene in 341 71% k. Outbreak of ndm1producing klebsiella pneumoniae in a dutch. Following this first description, sporadic cases of infected patients have been. Research note clearance of carbapenemaseproducing enterobacteriaceae cpe carriage. Antibioticresistant bacteria in indian public water.
Ndm 1 functions through two zinc ions present in the active site that cause hydrolysis of the betalactams, rendering them ineffective. Thetransference of bla ndm 1 to a recipient strain was achieved for strains. Clearance of carbapenemaseproducing enterobacteriaceae cpe. The recent examples of transcontinental spread of the severe acute respiratory syndrome sars virus from guangdong province in china to hong kong and then canada in 2003, and the ndm 1 carbapenemase, which inactivates all. Carbapenem resistance in klebsiella pneumoniae due to the new delhi metallo. To determine the buffer effect, ndm1 activity in 40 mm ethanolamine buffer at ph 10 and 11 was observed. Embelin, an important ingredient in traditional herbal medicine, has antitumor effects. Spread of plasmidencoded ndm 1 and ges5 carbapenemases among extensively drugresistant and pandrugresistant clinical enterobacteriaceae in durban, south africa february 2018 antimicrobial.
Structure, genetics and worldwide spread of new delhi metallo. The rapid pandemic spread of ndm1 bacteria worldwide spreading to india, pakistan, europe, america, and chinese taiwan in less than 2 months characterizes these microbes as a potentially major global health problem. The researchers found 6 ndm 1 producing isolates in india and pakistan and 37 in the united kingdom. The p271a plasmid carrying the bla ndm 1 gene was 35. We investigated the prevalence of ndm1, in multidrugresistant. Subsequently, timothy walsh and colleagues2 identified blandm 1 carrying bacterial species from the enterobacteriaceae, aeromonadaceae, vibrionaceae, and pseudomonadaceae, and some other non. Ndm 1 encoding plasmids are diverse and can also carry other antimicrobial resistance genes, including carbapenemase genes, esbl genes, plasmidmediated cephalosporinase genes, and aminoglycoside resistance genes 28, 29. Ndm 1 is reported to be highly resistant to all antibiotics.
The plasmidborne colistin resistance gene mcr 1 was initially identified in animal and clinical samples from china and subsequently reported worldwide, including in the united states. Nov, 2018 the serotype of all bla ndm 1 positive isolates was k64, while that of bla kpc2positive isolates were k47 n4 and k64 n2. Endemic indian clones of klebsiella pneumoniaeharbouring new. Dendrograms of strain relatedness were created with bionumerics software. However, most ndm 1 positive strains also express the cmy4 and ctxm15. Dissemination of ndm1 positive bacteria in the new delhi environment and its implications for human health. Coexistence of plasmidmediated mcr 1 and blandm4 genes in a klebsiella pneumoniae clinical strain in vietnam lien le, 1, linh khanh tran, 1, tamduong leha, 1 bichphuong tran, 1 hongngoc levo, 1 yennhi nguyen, 1 hanhlan nguyen, 1 khanhquynh hoangngoc, 1 yuki matsumoto,2 daisuke motooka,2 shota nakamura,2 james w jones,3 tetsuya iida,2,4 van cao1 1department of immunology and microbiology. To see a list of the latest blog entries on ndm 1 click this link update. It is among the worlds oldest, most prestigious, and best known general medical journals. In the netherlands, the number of cases of infection with new delhi metallobetalactamase ndm positive enterobacteriaceae is low.
Two hypotheses might explain a balkan association for blandm1. Ndm1 stands for a gene that produces new delhi metallobetalactamase in certain bacteria that cause infections. Crystal structure of new delhi metallolactamase reveals. Multidrugresistant klebsiella pneumoniae and escherichia coli isolates harboring new delhi metallo. Dissemination of ndm1 the lancet infectious diseases. New delhi metallobetalactamasee linkedin slideshare. Cooccurrence of bla ndm 1 with arma or with bla kpc2 genes was detected in two distinct eclstrains,e4ande3,respectively. The bla ndm1 gene is plasmid borne and encodes a metallo. New delhi, india, via the sentry antimicrobial surveillance program. Although discovered in 2008, ndm 1 positive enterobacteriaceae have attracted worldwide media attention due to their high incidence in india and.
The isolates were found to be sequence type 14 st14. Interestingly, although the identified bla ndm1 and bla oxa48 genes were conjugable, no household inhabitant was fecally colonized with a carbapenem resistant isolate. These genes can be passed easily between bacteria by. Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenemresistant gramnegative infections. In our study, however, the ndm 1 producing enterobacter spp. Cointroduction of plasmids harbouring the carbapenemase.
International surveillance of resistance, incorporating environmental sampling as well as examination of clinical isolates, needs to be established as a priority. Previous evidence showed that ndm producing bacteria are often susceptible to colistin, which has become the last resort for the treatment of infections due to ndm producing bacteria. At the time of hospital discharge, 12 of the 106 patients carrying ndm 1 cpe were clear of cpe, whereas none of the kpc cpe patients were ndm 1, 11. Emergence of ndm1producing klebsiella pneumoniae in. Sep 20, 2019 according to yoon et al, 3 the distribution of ndm. The lancet study selectively identified gramnegative enterobacteriaceae with resistance to carbapenem and named it as ndm1 isolated from guwahati. Two recent examples highlight the threat of emergence and rapid geographic dissemination of antibiotic resistance genes. Full text coproduction of mcr9 and ndm1 by colistin. Superbug bacteria producing ndm 1 enzyme causing wide public concern were first detected in a patient who visited india in 2008.
T o the e ditor infections caused by new delhi metallo. We therefore measured the prevalence of the ndm1 gene in drinking water and seepage samples in new delhi. One of the latest enzymes, ndm 1 new delhi metallo beta lactamase has been first identified from swedish patient of indian origin in 2008. Characterization of the first isolate of klebsiella. Archives of clinical infectious diseases phenotypic and. In the lancet infectious diseases, karthikeyan kumarasamy and colleagues1 reported that blandm 1 containing bacteria was isolated from a few patients in india, pakistan, and bangladesh. The current study aimed to determine the frequency of bla imp, bla vim, bla dim, bla aim, bla gim and bla ndm genes among p. All the 3 bla ndm positive isolates possessed the new delhi metallobetalactamase 1 ndm 1 allele with an inchi3 plasmid which was not transferable in one isolate. This patient travelled to new delhi and while there, acquired a urinary tract infection 4. A total of 147 patients carrying cpe, 106 with ndm 1 and 41 with kpc, were included in the study. The epub format is best viewed in the ibooks reader. Pdf version ndm 1 the newest recruit to the army of. Core components for infection prevention and control programmes.
Most bla ndm 1 carrying isolates contained bla ctxm15, bla oxa 1, bla oxa2 and bla tem 1 genes. The resistance is bestowed by a gene, bla ndm 1, that encodes the enzyme new delhi metallo. Apr 12, 2011 the report comes a few days after a study in lancet infectious diseases said bacteria with ndm 1 new delhi metallobetalactamase 1, an enzyme that makes gramnegative bacteria resistant to nearly all antibiotics, was found in drinking and seepage water in new delhi. Ndm1producing klebsiella pneumoniae isolated in the. Coproduction of mcr9 and ndm1 by colistinresistant enterobacter hormaechei isolated from bloodstream infection yi yuan,1, ying li,2, guangxi wang,3 chengwen li,2 li xiang,3 junping she,3 yan yang,3 fangcai zhong,1 luhua zhang3 1department of clinical laboratory, the first peoples hospital of neijiang, sichuan, peoples republic of china. Of particular concern is the spread of mcr 1 into carbapenemresistant bacteria. Most ndm1 strains are resistant to all commonly used antibiotics. Travel makes patients venerable the superbug called new delhi metallo betalactamase, or ndm 1, was identified in 50 people who traveled to india or pakistan for surgery and then returned to the united kingdom, british scientists reported in the journal lancet infectious dr. In a very recent study, the most frequently detected sts found in clinical isolates of ndm1producing k.
The development of the fosa3bla ndm 9 resistance region was mediated by is26. The newspaper said the ncdc yielded to pressure after days of denying the. In our research, we designed ten oligopeptides, tested ic50 values against ndm 1 enzyme, determined the mic values of synergistic. Ndm 1, an acronym for new delhi metallolactamase 1, was identified last year after an indian hospital admitted a patient from sweden. Household cockroaches carry ctxm15, oxa48 and ndm1. Subsequently, timothy walsh and colleagues2 identified blandm 1 carrying bacterial species from the enterobacteriaceae, aeromonadaceae, vibrionaceae, and pseudomonadaceae, and some other nonfermenters, in new. Clearance of carbapenemaseproducing enterobacteriaceae. The ndm 1 producing hmkp isolates were positive for aerobactin, exhibited high serum resistance, and elicited significantly increased larval mortality compared with the other isolates. Molecular modeling and docking analysis of novel drug like. Plasmids carrying bla ndm 1 from the 14 isolates from haryana could not be typed. Oxa232, a variant of oxa48, was first reported in an e. We investigated the prevalence of ndm1, in multidrugresistant enterobacteriaceae in india, pakistan, and the uk. The introduction of ndm 1 into the uk is also very worrying and has prompted the release of a national resistance alert 3 notice by the department of health on the advice of the health protection agency. Ndm 1 stands for a gene that produces new delhi metallobetalactamase in certain bacteria that cause infections.
Potential inhibitors designed against ndm1 type metallo. The secondary structure of ndm 1 is shown as a grey ribbon, the modeled bound dcaptopril is shown as sticks in purple, the key residues bound to metal ions in ndm 1 and imp 1 are shown as golden and green sticks, and the residues that may also participate in dcaptopril binding in ndm 1 and imp 1 are shown as yellow and cyan sticks. Emergence of colistin resistance gene mcr1 in cronobacter. A major monoclonal hospital outbreak of ndm1producing. The data are entered directly onto the worksheets, and the user interface is shown in fig. Antibiotic resistance shows up in indias drinking water. Coproduction of mcr9 and ndm 1 by colistinresistant enterobacter hormaechei isolated from bloodstream infection yi yuan, 1, ying li,2, guangxi wang,3 chengwen li,2 li xiang,3 junping she,3 yan yang,3 fangcai zhong, 1 luhua zhang3 1department of clinical laboratory, the first peoples hospital of neijiang, sichuan, peoples republic of china. New delhi metallobetalactamase 1 ndm 1 is an enzyme that makes bacteria resistant to a broad range of betalactam antibiotics. Dissemination of ndm1 article pdf available in the lancet infectious diseases 122. A structural view of the antibiotic degradation enzyme ndm1. Dissemination of ndm1 positive bacteria in the new.
Ndm 1, which stands for new delhi metallobetalactamase 1, was first reported last year but jumped into the headlines last week with the publication of a lancet infectious diseases report on resistant bacteria in india and the united kingdom. The occurrence of ndm 1 in north america is a major public health concern. The journal was founded in 1823 by thomas wakley, an english surgeon who named it after the surgical instrument called a lancet scalpel, as well as after the architectural term lancet window, a window with a sharp pointed arch, to indicate. The indian response by members of parliament disputed the claim made in the august 2010 publication of the lancet that ndm 1 originated in india. Now, according to the chinet surveillance program, the prevalence of crec in the. Unusual association of ndm1 with kpc2 and arma among.
A total of 146 nonduplicate ndm producing enterobacteriaceae recovered between 2010 and 2015 were voluntarily collected from 33 general hospitals and confirmed by pcr. Mar 29, 2018 this study was carried out to investigate the epidemiological timecourse of new delhi metallobetalactamase ndm mediated carbapenem resistance in enterobacteriaceae in south korea. Screened compounds btb02323 m17 this compound bind within the active site of ndm 1 with a gold fitness score of 117. Realtime pcr assay allows detection of the new delhi metallo. Controversy over ndm1 superbug ignites uproar in india. Similarly, when the 32 randomly selected uk isolates were assessed with the same methods, 22 carried ac type plasmids. Builtin type identification automatically identifies this device as a monitor module to the control panel.
The serotype of all bla ndm 1 positive isolates was k64, while that of bla kpc2positive isolates were k47 n4 and k64 n2. Pdf while antibiotic resistance is quickly rising in gramnegative bacteria, the recent spread of a new. The ndm 1 gene was found on closely related incompatibility group ac type plasmids. The transferable ndm1 gene is identified in a variety of enterobacterial species, leading to. Carbapenemresistant escherichia coli crec is one of the major type of cre in the human gut. Sems screws with clamping plates for ease of wiring directdial entry of address. International travel increasing spread of new drug. We report the presence of mcr 1 in escherichia coli and carbapenemresistant cronobacter sakazakii from the same diseased chicken. In the strains, the bla ndm 1 and bla oxa232 genes are in different plasmids.
Oxa48 carbapenemases were initially identified in istanbul, turkey in 2001 8, 9. A major monoclonal hospital outbreak of ndm 1 producing klebsiella pneumoniae st340 and the first report of st2570 in brazil volume 40 issue 4 jussimara monteiro, fernanda m. The report comes a few days after a study in lancet infectious diseases said bacteria with ndm 1 new delhi metallobetalactamase 1, an enzyme that makes gramnegative bacteria resistant to nearly all antibiotics, was found in drinking and seepage water in new delhi. The serotype of all bla ndm 1 positive isolates was k64, while that of bla kpc2positive isolates were k47 n4 and k64. Realtime pcr assay allows detection of the new delhi. Spread of plasmidencoded ndm1 and ges5 carbapenemases. Emergence of a new antibiotic resistance mechanism in india. The bla ndm1 gene has been identified mostly in nonclonally related isolates of e. Core components for infection prevention and control.
The resistome of the multidrugresistant escherichia coli strain 271 carrying the plasmidmediated bla ndm 1 carbapenemase gene was analyzed by highthroughput genome sequencing. The mcr 1 gene linked with isapl1 was located on two different inci2 plasmids, including one multidrug plasmid in e. The new delhi metallobetalactamase ndm 1 is a novel type of mbl named after the city of origin, which has been recently criticized, following a common practice with transferable mbls since vim 1 was named after verona, italy 5. All ecl isolates carried bla ctxm15 and possessed different pfge patterns. Magnolol restores the activity of meropenem against ndm1. In addition, the co existence of blandm and mcr1 was found in 14 crec, which. In row 3 you can see the section title typeset in bold, and examples of indicators are in rows 45. Emergence of multidrugresistant providencia rettgeri. Meanwhile, afp is reporting the first ndm 1 related death, an. Only reproduce with permission from the lancet publishing group. Led indication for normal or off normal indication. Jan 25, 2018 the emergence and spread of carbapenemase in gramnegative pathogens poses an enormous threat to global public health.
In ghana, there are no published data on carbapenemases, but it is the experience that carbapenem resistance is low 6. Dissemination of ndm 1 positive bacteria in the new delhi environment and its implications for human health. History of travel in india could be traced for four patients from whom ndm 1 producing k. Full text coexistence of plasmidmediated mcr1 and blandm.
A substantially increasing trend of ndm 1 producing k. The health ministry in india asserted that the alarm was spurred by western doctors fearing loss of business to india by way. Among these, most esbls found with ndm 1 have been reported to be as ctxm15 type 29, 30. Identification and characterization of ndm1producing. The emergence of plasmidmediated new delhi metallo. These include the antibiotics of the carbapenem family ertapenem, imipenem, doripenem and meropenem, which are a mainstay for the. Pfge analysis clustered ndm 1 producers into five distinct clonal types, with five.
Bacteria with the ndm1 gene are part of a larger group of superbug bacteria that are extremely hard to treat and can spread easily in hospitals. Compared to the plasmid bearing bla ndm 1, the plasmid with bla oxa232, a coletype plasmid, is very small about 6000 bp. An enzyme that confers resistance to a wide range of antibiotics, new delhi metallobetalactamase 1 ndm 1, has emerged in the indian subcontinent and spread to the uk as a result of medical tourism after first being detected in 2008 yong et al. The title of a core component and the resulting score for the whole component are in row 1, and the headings of the main fields are in row 2. Molecular characterization of ndm 1 producing enterobacteriaceae isolates in singapore hospitals original research jeanette teo, a grace ngan, a michelle balm, a roland jureen, a prabha krishnan b and raymond lin a a department of laboratory medicine, national university hospital, singapore 119074. Seven were positive for bla ndm 1 and shared the same genotype pt5st1764.
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