Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At p...Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.展开更多
Objective: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-β-lactamase (NDM)-producing bacteria. Data Sources: We searched database for studies published in English. The ...Objective: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-β-lactamase (NDM)-producing bacteria. Data Sources: We searched database for studies published in English. The database of PubMed from 2007 to 2015 was used to conduct a search using the keyword term "NDM and Acinetobacter or Enterobacteriaceae or Pseudomonas aeruginosa." Study Selection: We collected data including the relevant articles on international transmission, testing methods and treatment strategies of NDM-positive bacteria. Worldwide NDM cases were reviewed based on 22 case reports. Results: The first documented case of infection caused by bacteria producing NDM- 1 occurred in India, in 2008. Since then, 13 blaNDM variants have been reported. The rise of NDM is not only due to its high rate of genetic transfer among unrelated bacterial species, but also to human factors such as travel, sanitation and food production and preparation. With limited treatment options, scientists try to improve available therapies and create new ones. Conclusions: In order to slow down the spread of these NDM-positive bacteria, a series of measures must be implemented. The creation and transmission of blaNDM are potentially global health issues, which are not issues for one country or one medical community, but for global priorities in general and for individual wound care practitioners specifically.展开更多
Background:The uroculturome indicates the profile of culturable microbes inhabiting the urinary tract,and it is often required to do a urine culture to find an effective antimicrobial to treat urinary tract infections...Background:The uroculturome indicates the profile of culturable microbes inhabiting the urinary tract,and it is often required to do a urine culture to find an effective antimicrobial to treat urinary tract infections(UTIs).Methods:This study targeted to understand the profile of culturable pathogens in the urine of apparently healthy(128)and humans with clinical UTIs(161)and their antimicrobial susceptibility.All the urine samples were analyzed to quantify microbial load and determine the diversity and antimicrobial susceptibility of microbes following standard microbiological methods.Results:In urine samples from UTI cases,microbial counts were 1.2×10^(4)±6.02×10^(3) colony-forming units(cfu)/mL,while in urine samples from apparently healthy humans,the average count was 3.33±1.34×10^(3) cfu/mL.In eight samples(six from UTI cases and two from apparently healthy people,Candida(C.albicans 3,C.catenulata 1,C.krusei 1,C.tropicalis 1,C.parapsiplosis 1,C.gulliermondii 1)and Rhizopus species(1)were detected.Candida krusei was detected only in a single urine sample from a healthy person and C.albicans was detected both in urine of healthy and clinical UTI cases.Gram-positive(G+ve)bacteria were more commonly(Odds ratio,1.98;CI99,1.01-3.87)detected in urine samples of apparently healthy humans,and Gram-negative(G−ve)bacteria(Odds ratio,2.74;CI99,1.44-5.23)in urines of UTI cases.From urine samples of 161 UTI cases,a total of 90 different types of microbes were detected and,73 samples had only a single type of bacteria.In contrast,49,29,3,4,1,and 2 samples had 2,3,4,5,6 and 7 types of bacteria,respectively.The most common bacteria detected in urine of UTI cases was Escherichia coli(52 samples),in 20 cases as the single type of bacteria,other 34 types of bacteria were detected in pure form in 53 cases.From 128 urine samples of apparently healthy people,88 types of microbes were detected either singly or in association with others,from 64 urine samples only a single type of bacteria was detected while 34,13,3,11,2 and 1 sample yielded 2,3,4,5,6 and seven types of microbes,respectively.In the urine of apparently healthy humans too,E.coli was the most common bacteria,(10 samples)followed by Staphylococcus haemolyticus(9),S.intermedius(5),and S.aureus(5),and similar types of bacteria also dominated in cases of mixed occurrence,E.coli was detected in 26,S.aureus in 22 and S.haemolyticus in 19 urine samples,respectively.G+ve bacteria isolated from urine samples’irrespective of health status were more often(P<0.01)resistant than G−ve bacteria to ajowan oil,holy basil oil,cinnamaldehyde,and cinnamon oil,but more susceptible to sandalwood oil(P<0.01).However,for antibiotics,G+ve were more often susceptible than G−ve bacteria to cephalosporins,doxycycline,and nitrofurantoin.Conclusion:The study concludes that to understand the role of good and bad bacteria in the urinary tract microbiome more targeted studies are needed to discern the isolates at the pathotype level.Further,the study suggests the use of antibiotics by observing good antibiotic stewardship following antibiotic susceptibility testing only.展开更多
Background: Carbapenem resistant extended spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae (K. pneumoniae) is increasing worldwide. Carbapenem resistance (CR) has been attributed not only to production of ...Background: Carbapenem resistant extended spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae (K. pneumoniae) is increasing worldwide. Carbapenem resistance (CR) has been attributed not only to production of carbapenemases but also to permeability barriers due to outer membrane proteins (OmpK35 and OmpK36) disruption. Objective: Phenotypic detection of CR among ESBL producing K. pneumoniae isolates, followed by the evaluation of the role of ompK35 and ompK36 gene expression among carbapenem resistant K. pneumoniae (CR-KP) isolates. Methods: 100 ESBL producing K. pneumoniae isolates were included in this study. Minimum inhibitory concentration (MIC) of imipenem was performed for all isolates by broth microdilution method. For CR-KP isolates, phenotypic detection of K. pneumoniae carbapenemase (KPC), metallo-β-lactamase (MBL) and AmpC enzymes was performed followed by Realtime qRT-PCR to detect and quantify ompK35 and ompK36 gene expression. Results: 42% of our isolates were carbapenem resistant, and all of them were KPC producers either singly or in combination with MBL and/or AmpC production. Reduced expression of both ompK35 and ompK36 was detected in (52.38%) of CR-KP isolates, while reduced expression of ompK36 or ompK35 alone was found in (2.38%) and (33.33%) respectively. Twenty of 42 CR-KP isolates (47.62%), showing reduced ompK35 and ompK36 expression, exhibited high level resistance (HLR) (>32 μg/ml) to imipenem. There was a significant correlation between reduced expression of ompK36 and increase MIC values (p < 0.05). The combined production of MBL or AmpC together with reduced expression of ompK35 and/or ompK36 resulted in significant increase in imipenem MIC (p < 0.05). Conclusion: The combined OmpK35/OmpK36 loss resulted in HLR. However OmpK36 seems to play a major role in those strains. Imipenem MIC was markedly increased among K. pneumoniae showing carbapenemase and/or AmpC production together with loss of OmpK35 and/or OmpK36.展开更多
Background: Multi-drug resistant and Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections present a significant challenge in hospital ICU settings worldwide and the threat posed is worse in developing countr...Background: Multi-drug resistant and Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections present a significant challenge in hospital ICU settings worldwide and the threat posed is worse in developing countries including Kenya. Despite the limited treatment options, there is inadequate comprehensive data on factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at hospitals. This study therefore aimed to address this gap and determined risk factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at MOI Teaching and Referral Hospital, Kenya. Methods: Through cross-sectional study design, a total of 132 ICU admitted patients were purposively enrolled in this study between July 2019 and July 2020. Demographic and risk factors associated with MDR and CR Acinobacter baumannii were collected using structured questionnaire. Descriptive statistics and bivalent analysis were used for data analysis obtained. Level of statistical significance was 95% confidence interval (CI) for all analysis. Results: Bivariable analysis showed that employed participants were 3.4 times more likely to have A. baumannii compared to the unemployed (cOR = 3.38, 95%, CI: 1.09 - 10.43, p = 0.035). Patients who were having high BMI were likely to be infected by A. baumannii compared to those who had normal/low BMI (aOR = 11.2, 95%, CI: 3.57 - 21.11, p = 0.004). Those who were aged ≥ 50 years were 21 times more likely to be carbapenem-resistant Acinetobacter baumannii, COR = 21.0, 95% CI: 1.83 - 240.52, p = 0.011. Those who stayed in ICU for more than 30 days were 16 times more likely to be carbapenem-resistant Acinetobacter baumannii compared to those who had been admitted (COR = 16.0, 95% CI: 1.45 - 176.45, p = 0.019). Conclusion: Increased length of hospital stay, obesity and marital status were the factors found to be significantly associated with A. baumannii infections among ICU admitted patients. On the other hand, gender, age, level of education, occupation, referral status and presence of infection were found to have no significant association with A. baumannii infections among ICU admitted patients. All patients admitted to the intensive care units should be screened for colonization with A. baumannii, owing to the poor treatment outcomes associated with carriage of this multidrug resistant pathogen. Proper infection control in the ICU settings should be upheld to mitigate the spread of A. baumannii in the intensive care units.展开更多
Acinetobacter baumannii is a frequent cause of nosocomial infections.Here we report an intermittent outbreak caused by the emerging carbapenem-resistant A.baumannii(CRAB)clone ST457 and assess the effectiveness of pat...Acinetobacter baumannii is a frequent cause of nosocomial infections.Here we report an intermittent outbreak caused by the emerging carbapenem-resistant A.baumannii(CRAB)clone ST457 and assess the effectiveness of patient screening for outbreak control.CRAB isolates were collected from 74 patients admitted to the respiratory intensive care unit of a tertiary hospital between May 2018 and March 2019.Fourteen CRAB isolates were assigned to ST457,and 13 belonged to an outbreak clone,as determined by phylogenomic analysis.Strict patient screening was started at the respiratory intensive care unit on May 2019,through which a ST457-positive patient transferred from the intensive care unit was detected.No positive patients were detected within 3months onwards.The results of this study highlight the importance of rigorous infection prevention and control measures,combined with patient screening,in controlling the CRAB outbreak.展开更多
Carbapenem is one of the few available drugs to treat multidrug-resistance Gram-negative bacteria infections.Recently,the plasmid-mediated spread of the carbapenem resistance gene blaNDM poses a significant threat to ...Carbapenem is one of the few available drugs to treat multidrug-resistance Gram-negative bacteria infections.Recently,the plasmid-mediated spread of the carbapenem resistance gene blaNDM poses a significant threat to public health,requiring global monitoring and surveillance.Here,we used both short-read(n=2461)and long-read(n=546)sequencing data to characterize the global distribution of bla_(NDM).We analyzed the replicon type of bla_(NDM)-positive plasmids and found that the dominant plasmid type was different in diverse geographical locations.Although bla_(NDM)gene has been transferred across diverse countries,its genetic backgrounds are highly conserved,and the mobile genetic element ISAba125,IS5,and IS26 may play an important role in the mobilization of bla_(NDM).A significant association was observed between host origin and gene presence/deletion variation on IncX3 plasmid,which may be a key factor in the bacterial adaption to diverse hosts.In this study,we analyzed the diversity,distribution and transmission of bla_(NDM)-positive plasmids from a global perspective,and emphasize the importance of plasmid analysis for understanding the evolution and adaptation of bla_(NDM)-positive plasmids and their co-evolution with bacterial genomes(resistome).展开更多
基金supported in part by the grants from National Natural Science Foundation of China(81991535,81861138051,and 81871690)UK MRC DETER-XDR-China-HUB(MR/S013768/1)。
文摘Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.
基金Source of Support: This study was supported by grants from National Natural Science Foundation of China (No. 81101288 and 81172737). Conflict of Interest: None declared.
文摘Objective: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-β-lactamase (NDM)-producing bacteria. Data Sources: We searched database for studies published in English. The database of PubMed from 2007 to 2015 was used to conduct a search using the keyword term "NDM and Acinetobacter or Enterobacteriaceae or Pseudomonas aeruginosa." Study Selection: We collected data including the relevant articles on international transmission, testing methods and treatment strategies of NDM-positive bacteria. Worldwide NDM cases were reviewed based on 22 case reports. Results: The first documented case of infection caused by bacteria producing NDM- 1 occurred in India, in 2008. Since then, 13 blaNDM variants have been reported. The rise of NDM is not only due to its high rate of genetic transfer among unrelated bacterial species, but also to human factors such as travel, sanitation and food production and preparation. With limited treatment options, scientists try to improve available therapies and create new ones. Conclusions: In order to slow down the spread of these NDM-positive bacteria, a series of measures must be implemented. The creation and transmission of blaNDM are potentially global health issues, which are not issues for one country or one medical community, but for global priorities in general and for individual wound care practitioners specifically.
基金supported by grants received from CAAST-ACLH(NAHEP/CAAST/2018-19)of ICAR-World Bank-funded National Agricultural Higher Education Project(NAHEP).
文摘Background:The uroculturome indicates the profile of culturable microbes inhabiting the urinary tract,and it is often required to do a urine culture to find an effective antimicrobial to treat urinary tract infections(UTIs).Methods:This study targeted to understand the profile of culturable pathogens in the urine of apparently healthy(128)and humans with clinical UTIs(161)and their antimicrobial susceptibility.All the urine samples were analyzed to quantify microbial load and determine the diversity and antimicrobial susceptibility of microbes following standard microbiological methods.Results:In urine samples from UTI cases,microbial counts were 1.2×10^(4)±6.02×10^(3) colony-forming units(cfu)/mL,while in urine samples from apparently healthy humans,the average count was 3.33±1.34×10^(3) cfu/mL.In eight samples(six from UTI cases and two from apparently healthy people,Candida(C.albicans 3,C.catenulata 1,C.krusei 1,C.tropicalis 1,C.parapsiplosis 1,C.gulliermondii 1)and Rhizopus species(1)were detected.Candida krusei was detected only in a single urine sample from a healthy person and C.albicans was detected both in urine of healthy and clinical UTI cases.Gram-positive(G+ve)bacteria were more commonly(Odds ratio,1.98;CI99,1.01-3.87)detected in urine samples of apparently healthy humans,and Gram-negative(G−ve)bacteria(Odds ratio,2.74;CI99,1.44-5.23)in urines of UTI cases.From urine samples of 161 UTI cases,a total of 90 different types of microbes were detected and,73 samples had only a single type of bacteria.In contrast,49,29,3,4,1,and 2 samples had 2,3,4,5,6 and 7 types of bacteria,respectively.The most common bacteria detected in urine of UTI cases was Escherichia coli(52 samples),in 20 cases as the single type of bacteria,other 34 types of bacteria were detected in pure form in 53 cases.From 128 urine samples of apparently healthy people,88 types of microbes were detected either singly or in association with others,from 64 urine samples only a single type of bacteria was detected while 34,13,3,11,2 and 1 sample yielded 2,3,4,5,6 and seven types of microbes,respectively.In the urine of apparently healthy humans too,E.coli was the most common bacteria,(10 samples)followed by Staphylococcus haemolyticus(9),S.intermedius(5),and S.aureus(5),and similar types of bacteria also dominated in cases of mixed occurrence,E.coli was detected in 26,S.aureus in 22 and S.haemolyticus in 19 urine samples,respectively.G+ve bacteria isolated from urine samples’irrespective of health status were more often(P<0.01)resistant than G−ve bacteria to ajowan oil,holy basil oil,cinnamaldehyde,and cinnamon oil,but more susceptible to sandalwood oil(P<0.01).However,for antibiotics,G+ve were more often susceptible than G−ve bacteria to cephalosporins,doxycycline,and nitrofurantoin.Conclusion:The study concludes that to understand the role of good and bad bacteria in the urinary tract microbiome more targeted studies are needed to discern the isolates at the pathotype level.Further,the study suggests the use of antibiotics by observing good antibiotic stewardship following antibiotic susceptibility testing only.
文摘Background: Carbapenem resistant extended spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae (K. pneumoniae) is increasing worldwide. Carbapenem resistance (CR) has been attributed not only to production of carbapenemases but also to permeability barriers due to outer membrane proteins (OmpK35 and OmpK36) disruption. Objective: Phenotypic detection of CR among ESBL producing K. pneumoniae isolates, followed by the evaluation of the role of ompK35 and ompK36 gene expression among carbapenem resistant K. pneumoniae (CR-KP) isolates. Methods: 100 ESBL producing K. pneumoniae isolates were included in this study. Minimum inhibitory concentration (MIC) of imipenem was performed for all isolates by broth microdilution method. For CR-KP isolates, phenotypic detection of K. pneumoniae carbapenemase (KPC), metallo-β-lactamase (MBL) and AmpC enzymes was performed followed by Realtime qRT-PCR to detect and quantify ompK35 and ompK36 gene expression. Results: 42% of our isolates were carbapenem resistant, and all of them were KPC producers either singly or in combination with MBL and/or AmpC production. Reduced expression of both ompK35 and ompK36 was detected in (52.38%) of CR-KP isolates, while reduced expression of ompK36 or ompK35 alone was found in (2.38%) and (33.33%) respectively. Twenty of 42 CR-KP isolates (47.62%), showing reduced ompK35 and ompK36 expression, exhibited high level resistance (HLR) (>32 μg/ml) to imipenem. There was a significant correlation between reduced expression of ompK36 and increase MIC values (p < 0.05). The combined production of MBL or AmpC together with reduced expression of ompK35 and/or ompK36 resulted in significant increase in imipenem MIC (p < 0.05). Conclusion: The combined OmpK35/OmpK36 loss resulted in HLR. However OmpK36 seems to play a major role in those strains. Imipenem MIC was markedly increased among K. pneumoniae showing carbapenemase and/or AmpC production together with loss of OmpK35 and/or OmpK36.
文摘Background: Multi-drug resistant and Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections present a significant challenge in hospital ICU settings worldwide and the threat posed is worse in developing countries including Kenya. Despite the limited treatment options, there is inadequate comprehensive data on factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at hospitals. This study therefore aimed to address this gap and determined risk factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at MOI Teaching and Referral Hospital, Kenya. Methods: Through cross-sectional study design, a total of 132 ICU admitted patients were purposively enrolled in this study between July 2019 and July 2020. Demographic and risk factors associated with MDR and CR Acinobacter baumannii were collected using structured questionnaire. Descriptive statistics and bivalent analysis were used for data analysis obtained. Level of statistical significance was 95% confidence interval (CI) for all analysis. Results: Bivariable analysis showed that employed participants were 3.4 times more likely to have A. baumannii compared to the unemployed (cOR = 3.38, 95%, CI: 1.09 - 10.43, p = 0.035). Patients who were having high BMI were likely to be infected by A. baumannii compared to those who had normal/low BMI (aOR = 11.2, 95%, CI: 3.57 - 21.11, p = 0.004). Those who were aged ≥ 50 years were 21 times more likely to be carbapenem-resistant Acinetobacter baumannii, COR = 21.0, 95% CI: 1.83 - 240.52, p = 0.011. Those who stayed in ICU for more than 30 days were 16 times more likely to be carbapenem-resistant Acinetobacter baumannii compared to those who had been admitted (COR = 16.0, 95% CI: 1.45 - 176.45, p = 0.019). Conclusion: Increased length of hospital stay, obesity and marital status were the factors found to be significantly associated with A. baumannii infections among ICU admitted patients. On the other hand, gender, age, level of education, occupation, referral status and presence of infection were found to have no significant association with A. baumannii infections among ICU admitted patients. All patients admitted to the intensive care units should be screened for colonization with A. baumannii, owing to the poor treatment outcomes associated with carriage of this multidrug resistant pathogen. Proper infection control in the ICU settings should be upheld to mitigate the spread of A. baumannii in the intensive care units.
基金This work was supported by the National Key Research and Development Program of China(2017YFC1200200)Major Infectious Diseases Such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects(2018ZX10712-001)+2 种基金the National Natural Science Foundation of China(81902030)Shenzhen Basic Research Key projects(JCYJ20200109144220704)Shenzhen Basic Research projects(JCYJ20190807144409307).
文摘Acinetobacter baumannii is a frequent cause of nosocomial infections.Here we report an intermittent outbreak caused by the emerging carbapenem-resistant A.baumannii(CRAB)clone ST457 and assess the effectiveness of patient screening for outbreak control.CRAB isolates were collected from 74 patients admitted to the respiratory intensive care unit of a tertiary hospital between May 2018 and March 2019.Fourteen CRAB isolates were assigned to ST457,and 13 belonged to an outbreak clone,as determined by phylogenomic analysis.Strict patient screening was started at the respiratory intensive care unit on May 2019,through which a ST457-positive patient transferred from the intensive care unit was detected.No positive patients were detected within 3months onwards.The results of this study highlight the importance of rigorous infection prevention and control measures,combined with patient screening,in controlling the CRAB outbreak.
基金supported by the Laboratory of Lingnan Modern Agriculture Project(NT2021006)National Natural Science Foundation of China(32273054).
文摘Carbapenem is one of the few available drugs to treat multidrug-resistance Gram-negative bacteria infections.Recently,the plasmid-mediated spread of the carbapenem resistance gene blaNDM poses a significant threat to public health,requiring global monitoring and surveillance.Here,we used both short-read(n=2461)and long-read(n=546)sequencing data to characterize the global distribution of bla_(NDM).We analyzed the replicon type of bla_(NDM)-positive plasmids and found that the dominant plasmid type was different in diverse geographical locations.Although bla_(NDM)gene has been transferred across diverse countries,its genetic backgrounds are highly conserved,and the mobile genetic element ISAba125,IS5,and IS26 may play an important role in the mobilization of bla_(NDM).A significant association was observed between host origin and gene presence/deletion variation on IncX3 plasmid,which may be a key factor in the bacterial adaption to diverse hosts.In this study,we analyzed the diversity,distribution and transmission of bla_(NDM)-positive plasmids from a global perspective,and emphasize the importance of plasmid analysis for understanding the evolution and adaptation of bla_(NDM)-positive plasmids and their co-evolution with bacterial genomes(resistome).