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
Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacte...Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].展开更多
Objective The aim of our study is to investigate the prevalence of Carbapenem-resistant Klebsiella pneumoniae （CRKP） and the genetic characteristics of the class 1 integron in CRKP on multi-drug resistance. Methods...Objective The aim of our study is to investigate the prevalence of Carbapenem-resistant Klebsiella pneumoniae （CRKP） and the genetic characteristics of the class 1 integron in CRKP on multi-drug resistance. Methods Clinical Klebsiella pneumoniae strains were collected from multiple departments of a hospital in central China. CRKP strains were identified among the isolates, and antibiotics susceptibility of CRKP strains was analyzed. The polymerase chain reaction （PCR） was adopted to amplify the class 1 integron variable area. The integron genetic structure was analyzed with enzyme digestion and DNA sequencing technology. The relation between class 1 integron and drug resistance was analyzed statistically. Results Totally 955 strains of Klebsiella pneumoniae were isolated from varied sites of the hospital, and 117（12.3%） of them were identified as CRKP, with a separation rate of 8.9% （26/292） in 2013, 11.3% （38/336） in 2014 and 16.2% （53/327） in 2015, which shows an increasing trend by year. 44.4% （52/117） of CRKP strains were separated from specimen of ICU, and 61.5% （72/117） were from sputum. Over 95% CRKP strains were resistant to ampicillin/sulbactam, aztreonam, imipenem, meropenem Ceftazidme,Cefotaxime,Cefepime,and Piperacillin, while relatively low resistant rates were found in Tigecycline （12.8%） and colistin （35.9%）. The class 1 integron was detected in 77.8% （91/117） of CRKP strains. Class 1 integron of CRKP was significantly correlated with the antibiotic resistance to the tobramycin, gentamicin and amikacin （all P〈0.01）. The gene cassette analysis of variable area of class 1 integron showed that aadA2 accounts for 64.8% （59/91）, aacA4-catB8-aadA1 23.1% （21/91）, and aadA2-dfrA25 12.1% （11/91）. Conclusions CRKP has an increasing trend in a clinical setting in China, and most of them were resistant to multiple antibiotics. Class 1 integron in CRKP has strong ability to capture the genes resistant to aminoglycosides antibiotics from environment, with the aadA2 gene as the most popular one.展开更多
Background:Achromobacter xylosoxidans(A.xylosoxidans)subspecies strains are known to be opportunistic environmental inhabitants.Among the two species,A.xylosoxidans ssp.xylosoxidans is more commonly reported cause of ...Background:Achromobacter xylosoxidans(A.xylosoxidans)subspecies strains are known to be opportunistic environmental inhabitants.Among the two species,A.xylosoxidans ssp.xylosoxidans is more commonly reported cause of nosocomial infections colonizing the hospital environment and medical devices,while A.xylosoxidans ssp.denitrificans(AD)strains are widely distributed in the abiotic environment.The present retrospective observational study was aimed at understanding the occurrence of AD infections in the Bareilly region,and to look into the effective herbal and conventional antimicrobial resistance profile of the strains identified at the laboratory.Methods:The present retrospective study analysed Clinical Microbiology laboratory data of Indian veterinary research Institute.The data for the last 14 years(2011-2024)was retrieved,tabulated and analysed using MS Excel program to determine significance of occurrence,and variation in antimicrobial resistance of the strains isolated from different sources usingχ2 and odds ratio analysis.Results:The study revealed that AD was detectable as a potential pathogen not only from environmental samples but also from 51 clinical cases(either as pure culture or mixed infection),and also from healthy humans and animals.The pathogen was most commonly associated with deaths in animals and birds due to septicaemia and was isolated is single pathogen from blood samples.It was also detected as single pathogen from cases of abortions,metritis,and urinary tract infections.However,from cases of haemorrhagic enteritis,diarrhoea,mastitis,wound infections,pyoderma and abscesses,and middle ear infections AD was isolated in association of one or more potentially pathogenic bacteria.Of the 80 isolates in the study,68 had multiple drug resistance,and 21 produced metallo-β-lactamases responsible for resistance against most of theβ-lactam antibiotics,including cephalosporins and carbapenems.The most effective antibiotic was gentamicin,inhibiting 90.67%of the isolates,followed by tigecycline(85.00%),ciprofloxacin(80.77%),piperacillin tazobactam(80.65%);other antibiotics were effective against less than 80%of the isolates.Among the herbal antimicrobials,cinnamaldehyde,cinnamon oil,carvacrol,and ajowan oil inhibited 98.41%,85.07%,85.00%,and 83.75%of the isolates,respectively.Conclusion:The study concluded that in the Bareilly region in India,multiple-drug-resistance AD may be an emerging pathogen prevalent in environment and apparently healthy animals.More studies are warranted to understand the AD strains at molecular level to understand their zoonotic potential and circulation in the environment.展开更多
Antimicrobial resistance(AMR)has become a critical global public health challenge in the 21st century.Since the initial isolation of a blaNDM-1-carrying and carbapenem-resistant Klebsiella pneumoniae from an Indian ho...Antimicrobial resistance(AMR)has become a critical global public health challenge in the 21st century.Since the initial isolation of a blaNDM-1-carrying and carbapenem-resistant Klebsiella pneumoniae from an Indian hospital in 2009[1],the escalating prevalence of New Delhi metallo-β-lactamase(NDM)-encoding genes(blaNDM)has transformed carbapenem resistance into a worldwide phenomenon,transcending national and regional boundaries[2].Up to 90 distinct NDM variants have been reported globally according to the NCBI GenBank Pathogens database.Plasmidmediated horizontal gene transfer(HGT),which occurs both within and across bacterial species,has significantly accelerated the global dissemination of blaNDM-related genes and the associated resistance[3].Carbapenem-resistant pathogens were responsible for 200,000 deaths globally in 2019[4].Although NDM-1 has been relatively well characterized[5],the epidemiological profiles of other NDM variants require continued surveillance and indepth investigation.The novel NDM-9 variant(GenBank accession no.KC999080)was first identified in 2013 from a clinically significant isolate of Klebsiella pneumoniae ST107 strain PPH1303 with a high level of resistance to carbapenems recovered from the urine culture of a pediatric patient in Beijing,China,who had acute lymphocytic leukemia and had undergone allogeneic stem cell transplantation[6].展开更多
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
Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(S...Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].展开更多
Objective To analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae(CRE)bloodstream infection(BSI)in patients with hematological diseases and to explore prognostic risk factors.M...Objective To analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae(CRE)bloodstream infection(BSI)in patients with hematological diseases and to explore prognostic risk factors.Methods This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022.The clinical features,carbapenemase test results,antimicrobial treatments,and outcomes were analyzed.Results A total of 120 patients developed CRE BSI.Escherichia coli(58/120,48.3%)was the most prevalent Enterobacteriaceae,followed by Klebsiella pneumoniae(52/120,43.3%).A total of 93 CRE strains were tested for carbapenemase,of which 75 strains produced carbapenemase(metalloenzyme:51 strains;serine enzyme:24 strains).The 30-day mortality rate after BSI was 24.2%(29/120).Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics(7.8%vs 36.2%,P<0.001).Moreover,initiating active therapy within 24 h of BSI onset significantly reduced mortality(15.0%us 33.3%,P=0.019).The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization(12 h:14.5%vs 34.1%,P=0.012;24 h:40.8%vs 65.9%,P=0.008).Multivariate analysis revealed that septic shock(HR=24.436,95%CI 4.148-143.966,P<0.001)and pulmonary infection(HR=9.346,95%CI 2.718-32.140,P<0.001)were independent risk factors for death within 30 days.Appropriate therapy was initiated within 24 h(HR=0.225,95%CI 0.059-0.851,P=0.028),and treatment with the ceftazidimeavibactam-containing regimen(HR=0.082,95%CI 0.018-0.362,P=0.001)significantly reduced mortality.Conclusion The prognosis of CRE BSI in patients with hematological diseases is poor.Timely,appropriatetherapyandd receipt of a ceftazidimeavibactamcontaining regimen can improve survival and prognosis.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
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
Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pne...Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.展开更多
Introduction:Salmonella 4,[5],12:i:-,a globally emerging pathogen with multidrug resistance(MDR),is spreading in China.Nationwide data on the antimicrobial resistance(AMR)and genomic characteristics of Salmonella 4,[5...Introduction:Salmonella 4,[5],12:i:-,a globally emerging pathogen with multidrug resistance(MDR),is spreading in China.Nationwide data on the antimicrobial resistance(AMR)and genomic characteristics of Salmonella 4,[5],12:i:-from human sources in China are scarce.This study aimed to characterize the prevalence,genetic diversity,and AMR profiles of Salmonella 4,[5],12:i:-in China.Methods:All information,including geographical data,antimicrobial susceptibility test results,and whole-genome sequences,was extracted from the Chinese Pathogen Identification Network database from 2017 to 2023.Antimicrobial resistance phenotypes of 2,736 human-derived isolates were determined,and genomic analysis was applied to assess their genetic heterogeneity.Additionally,resistance genes were detected.Results:Salmonella 4,[5],12:i:-strains exhibited varying levels of resistance to the tested antibiotics,with an overall resistance rate of 98.83%,MDR rate of 87.98%,and cefotaxime resistance of 25.91%.An increasing trend was observed for resistance to key antibiotics and AMR determinants from 2020–2023.Whole-genome analysis revealed five clades with high genetic diversity(A–E),with 97.33%belonging to ST34.Clade D carried a significant proportion of ESBL genes.Moreover,we identified 15 meropenemresistant isolates primarily harboring widely distributed plasmids containing multiple resistance genes,including blaNDM-5 and blaOXA-10.Conclusion:Salmonella 4,[5],12:i:-is highly sporadic in China but remains phylogenetically linked to the prevalent MDR clone with a distinct resistance profile worldwide.The emergence of elevated resistance to third-generation cephalosporins and sharp rise in carbapenem resistance,coupled with the detection of plasmid-mediated resistance determinants,suggests the evolution of endemic MDR clones circulating within China.These findings emphasize the need for enhanced surveillance,stricter regulations on antibiotic use in agriculture,comprehensive risk factor surveys,and targeted interventions to prevent outbreaks.展开更多
The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health.Carbapenem‐resistant Enterobacteriaceae(CRE),particularly those producing New Delhi Metallo‐β...The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health.Carbapenem‐resistant Enterobacteriaceae(CRE),particularly those producing New Delhi Metallo‐β‐lactamase(NDM‐CRE),are prevalent in livestock and have acquired resistance to nearly all commonly used β‐lactam antibiotics.This study evaluated the efficacy of the antimicrobial peptide BMAP‐27B,a derivative of the cathelicidin family,against NDM‐CRE strains in food animals.BMAP‐27B showed potent antibacterial activity and rapid bactericidal effects against CRE,as well as comparable effects against human carbapenem‐resistant Acinetobacter baumannii.Furthermore,BMAP‐27B effectively penetrated and cleared biofilms formed by virulent strains of Escherichia coli and Klebsiella pneumoniae.Mechanistic studies indicated that BMAP‐27B exerts its antibacterial activity by disrupting bacterial membranes and inhibiting bacterial energy metabolism.BMAP‐27B effectively enhances the efficacy of carbapenems against NDM‐positive isolates by inhibiting efflux pump activity and chelating Zn^(2+) to inhibit NDM proteases,thus reversing carbapenem resistance in NDM‐CRE.Importantly,BMAP‐27B maintained excellent antimicrobial stability under extreme pH changes and high salt concentrations,along with resistance to serum and protease degradation.Investigations revealed that BMAP‐27B also shows ideal biocompatibility and therapeutic efficacy in vivo.In summary,the highly potent antibacterial activity of BMAP‐27B,along with its potential role as a broadspectrum antibiotic adjuvant,makes it a promising candidate for combating infections caused by foodborne NDM‐CRE and preventing pathogen transmission at the animal‐human‐environment interface.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
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
Introduction:Carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a significant global public health threat.The dissemination of resistance is accelerated by plasmids harboring multiple carbapenemase genes,posing a p...Introduction:Carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a significant global public health threat.The dissemination of resistance is accelerated by plasmids harboring multiple carbapenemase genes,posing a particular challenge to the limited treatment options,including ceftazidimeavibactam.Methods:In this study,a CRKP strain,KpBSI024,was isolated from a patient with bloodstream infection in the intensive care unit of a tertiary hospital in China.The whole-genome sequencing combined with bioinformatic analysis was used to investigate the structural features of plasmids and associated resistance genes.In addition,conjugation experiments were conducted to assess the transferability of the resistance plasmid.Results:KpBSI024 exhibited resistance to carbapenems and ceftazidime-avibactam and was identified as sequence type ST1514.Whole-genome sequencing revealed that two carbapenemase genes,bla_(KPC-2) and bla_(IMP-4),coexisted on a 53 kb IncP6-type plasmid.This plasmid exhibited a complex structure,likely formed through multiple recombination events mediated by IS26 between plasmids of different Inc types.Although the resistance plasmid encodes a type IV secretion system,it lacks a relaxase gene and is therefore non-self-transmissible;however,it could be transferred at low frequency to Escherichia coli with the assistance of a conjugative plasmid.The growth of the transconjugants was not affected by the acquisition of the resistance plasmid,and they displayed resistance profiles to carbapenems and ceftazidime-avibactam similar to the donor strain.Conclusions:The coexistence of bla_(KPC-2) and bla_(IMP-4) on an IncP-type plasmid in a clinical K.pneumoniae isolate highlights the critical role of recombination events in the dissemination of resistance genes.The emergence of such multidrug-resistant plasmids underscores the urgent need for genomic surveillance and the development of innovative antimicrobial strategies to control the spread of highrisk resistance plasmids.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 bla_(NDM) poses a significant threat ...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 bla_(NDM) 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
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Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].
基金Supported by the Fund of Hubei 2011 Cooperative Innovation Center(2011JH-2013CXTT01)
文摘Objective The aim of our study is to investigate the prevalence of Carbapenem-resistant Klebsiella pneumoniae （CRKP） and the genetic characteristics of the class 1 integron in CRKP on multi-drug resistance. Methods Clinical Klebsiella pneumoniae strains were collected from multiple departments of a hospital in central China. CRKP strains were identified among the isolates, and antibiotics susceptibility of CRKP strains was analyzed. The polymerase chain reaction （PCR） was adopted to amplify the class 1 integron variable area. The integron genetic structure was analyzed with enzyme digestion and DNA sequencing technology. The relation between class 1 integron and drug resistance was analyzed statistically. Results Totally 955 strains of Klebsiella pneumoniae were isolated from varied sites of the hospital, and 117（12.3%） of them were identified as CRKP, with a separation rate of 8.9% （26/292） in 2013, 11.3% （38/336） in 2014 and 16.2% （53/327） in 2015, which shows an increasing trend by year. 44.4% （52/117） of CRKP strains were separated from specimen of ICU, and 61.5% （72/117） were from sputum. Over 95% CRKP strains were resistant to ampicillin/sulbactam, aztreonam, imipenem, meropenem Ceftazidme,Cefotaxime,Cefepime,and Piperacillin, while relatively low resistant rates were found in Tigecycline （12.8%） and colistin （35.9%）. The class 1 integron was detected in 77.8% （91/117） of CRKP strains. Class 1 integron of CRKP was significantly correlated with the antibiotic resistance to the tobramycin, gentamicin and amikacin （all P〈0.01）. The gene cassette analysis of variable area of class 1 integron showed that aadA2 accounts for 64.8% （59/91）, aacA4-catB8-aadA1 23.1% （21/91）, and aadA2-dfrA25 12.1% （11/91）. Conclusions CRKP has an increasing trend in a clinical setting in China, and most of them were resistant to multiple antibiotics. Class 1 integron in CRKP has strong ability to capture the genes resistant to aminoglycosides antibiotics from environment, with the aadA2 gene as the most popular one.
基金supported by grants from CAAST-ACLH(NAHEP/CAAST/2018-19)of the ICAR-World Bank-funded National Agricultural Higher Education Project(NAHEP).
文摘Background:Achromobacter xylosoxidans(A.xylosoxidans)subspecies strains are known to be opportunistic environmental inhabitants.Among the two species,A.xylosoxidans ssp.xylosoxidans is more commonly reported cause of nosocomial infections colonizing the hospital environment and medical devices,while A.xylosoxidans ssp.denitrificans(AD)strains are widely distributed in the abiotic environment.The present retrospective observational study was aimed at understanding the occurrence of AD infections in the Bareilly region,and to look into the effective herbal and conventional antimicrobial resistance profile of the strains identified at the laboratory.Methods:The present retrospective study analysed Clinical Microbiology laboratory data of Indian veterinary research Institute.The data for the last 14 years(2011-2024)was retrieved,tabulated and analysed using MS Excel program to determine significance of occurrence,and variation in antimicrobial resistance of the strains isolated from different sources usingχ2 and odds ratio analysis.Results:The study revealed that AD was detectable as a potential pathogen not only from environmental samples but also from 51 clinical cases(either as pure culture or mixed infection),and also from healthy humans and animals.The pathogen was most commonly associated with deaths in animals and birds due to septicaemia and was isolated is single pathogen from blood samples.It was also detected as single pathogen from cases of abortions,metritis,and urinary tract infections.However,from cases of haemorrhagic enteritis,diarrhoea,mastitis,wound infections,pyoderma and abscesses,and middle ear infections AD was isolated in association of one or more potentially pathogenic bacteria.Of the 80 isolates in the study,68 had multiple drug resistance,and 21 produced metallo-β-lactamases responsible for resistance against most of theβ-lactam antibiotics,including cephalosporins and carbapenems.The most effective antibiotic was gentamicin,inhibiting 90.67%of the isolates,followed by tigecycline(85.00%),ciprofloxacin(80.77%),piperacillin tazobactam(80.65%);other antibiotics were effective against less than 80%of the isolates.Among the herbal antimicrobials,cinnamaldehyde,cinnamon oil,carvacrol,and ajowan oil inhibited 98.41%,85.07%,85.00%,and 83.75%of the isolates,respectively.Conclusion:The study concluded that in the Bareilly region in India,multiple-drug-resistance AD may be an emerging pathogen prevalent in environment and apparently healthy animals.More studies are warranted to understand the AD strains at molecular level to understand their zoonotic potential and circulation in the environment.
基金supported financially by the National Key Research and Science Program of the Ministry of Science and Technology of the People’s Republic of China(2022YFC2303900)the Beijing Natural Science Foundation(7232242).
文摘Antimicrobial resistance(AMR)has become a critical global public health challenge in the 21st century.Since the initial isolation of a blaNDM-1-carrying and carbapenem-resistant Klebsiella pneumoniae from an Indian hospital in 2009[1],the escalating prevalence of New Delhi metallo-β-lactamase(NDM)-encoding genes(blaNDM)has transformed carbapenem resistance into a worldwide phenomenon,transcending national and regional boundaries[2].Up to 90 distinct NDM variants have been reported globally according to the NCBI GenBank Pathogens database.Plasmidmediated horizontal gene transfer(HGT),which occurs both within and across bacterial species,has significantly accelerated the global dissemination of blaNDM-related genes and the associated resistance[3].Carbapenem-resistant pathogens were responsible for 200,000 deaths globally in 2019[4].Although NDM-1 has been relatively well characterized[5],the epidemiological profiles of other NDM variants require continued surveillance and indepth investigation.The novel NDM-9 variant(GenBank accession no.KC999080)was first identified in 2013 from a clinically significant isolate of Klebsiella pneumoniae ST107 strain PPH1303 with a high level of resistance to carbapenems recovered from the urine culture of a pediatric patient in Beijing,China,who had acute lymphocytic leukemia and had undergone allogeneic stem cell transplantation[6].
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Guangdong Basic and Applied Basic Research Foundation(grant number 2024A1515010319 to J.Q.)Science and Technology Program of Shenzhen(grant numbers KCXFZ20230731100901003 to J.Q.and L.L.,KJZD20230923115116032 to J.Q.,JCYJ20190809144005609 to J.Q.)+1 种基金Shenzhen Key Laboratory of Biochip(grant number ZDSYS201504301534057 to J.Q.)Shenzhen High-level Hospital Construction Fund(to J.Q.).
文摘Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].
文摘Objective To analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae(CRE)bloodstream infection(BSI)in patients with hematological diseases and to explore prognostic risk factors.Methods This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022.The clinical features,carbapenemase test results,antimicrobial treatments,and outcomes were analyzed.Results A total of 120 patients developed CRE BSI.Escherichia coli(58/120,48.3%)was the most prevalent Enterobacteriaceae,followed by Klebsiella pneumoniae(52/120,43.3%).A total of 93 CRE strains were tested for carbapenemase,of which 75 strains produced carbapenemase(metalloenzyme:51 strains;serine enzyme:24 strains).The 30-day mortality rate after BSI was 24.2%(29/120).Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics(7.8%vs 36.2%,P<0.001).Moreover,initiating active therapy within 24 h of BSI onset significantly reduced mortality(15.0%us 33.3%,P=0.019).The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization(12 h:14.5%vs 34.1%,P=0.012;24 h:40.8%vs 65.9%,P=0.008).Multivariate analysis revealed that septic shock(HR=24.436,95%CI 4.148-143.966,P<0.001)and pulmonary infection(HR=9.346,95%CI 2.718-32.140,P<0.001)were independent risk factors for death within 30 days.Appropriate therapy was initiated within 24 h(HR=0.225,95%CI 0.059-0.851,P=0.028),and treatment with the ceftazidimeavibactam-containing regimen(HR=0.082,95%CI 0.018-0.362,P=0.001)significantly reduced mortality.Conclusion The prognosis of CRE BSI in patients with hematological diseases is poor.Timely,appropriatetherapyandd receipt of a ceftazidimeavibactamcontaining regimen can improve survival and prognosis.
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.
基金supported by the National Natural Science Foundation of China(grant numbers 81991531 to M.W.,82102440 to J.J.,and 32400149 to J.Z.).
文摘Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.
文摘Introduction:Salmonella 4,[5],12:i:-,a globally emerging pathogen with multidrug resistance(MDR),is spreading in China.Nationwide data on the antimicrobial resistance(AMR)and genomic characteristics of Salmonella 4,[5],12:i:-from human sources in China are scarce.This study aimed to characterize the prevalence,genetic diversity,and AMR profiles of Salmonella 4,[5],12:i:-in China.Methods:All information,including geographical data,antimicrobial susceptibility test results,and whole-genome sequences,was extracted from the Chinese Pathogen Identification Network database from 2017 to 2023.Antimicrobial resistance phenotypes of 2,736 human-derived isolates were determined,and genomic analysis was applied to assess their genetic heterogeneity.Additionally,resistance genes were detected.Results:Salmonella 4,[5],12:i:-strains exhibited varying levels of resistance to the tested antibiotics,with an overall resistance rate of 98.83%,MDR rate of 87.98%,and cefotaxime resistance of 25.91%.An increasing trend was observed for resistance to key antibiotics and AMR determinants from 2020–2023.Whole-genome analysis revealed five clades with high genetic diversity(A–E),with 97.33%belonging to ST34.Clade D carried a significant proportion of ESBL genes.Moreover,we identified 15 meropenemresistant isolates primarily harboring widely distributed plasmids containing multiple resistance genes,including blaNDM-5 and blaOXA-10.Conclusion:Salmonella 4,[5],12:i:-is highly sporadic in China but remains phylogenetically linked to the prevalent MDR clone with a distinct resistance profile worldwide.The emergence of elevated resistance to third-generation cephalosporins and sharp rise in carbapenem resistance,coupled with the detection of plasmid-mediated resistance determinants,suggests the evolution of endemic MDR clones circulating within China.These findings emphasize the need for enhanced surveillance,stricter regulations on antibiotic use in agriculture,comprehensive risk factor surveys,and targeted interventions to prevent outbreaks.
基金supported by a grant from the National Natural Science Foundation of China(Grants 32330004 to X.S.,and 32170130 to Y.W.)the Shanxi Fundamental Science Research Project for Chemistry&Biology(Grant No.22JHZ008 to X.S.)the Ningbo Top Medical and Health Research Program(No.2023020713 to X.S.).
文摘The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health.Carbapenem‐resistant Enterobacteriaceae(CRE),particularly those producing New Delhi Metallo‐β‐lactamase(NDM‐CRE),are prevalent in livestock and have acquired resistance to nearly all commonly used β‐lactam antibiotics.This study evaluated the efficacy of the antimicrobial peptide BMAP‐27B,a derivative of the cathelicidin family,against NDM‐CRE strains in food animals.BMAP‐27B showed potent antibacterial activity and rapid bactericidal effects against CRE,as well as comparable effects against human carbapenem‐resistant Acinetobacter baumannii.Furthermore,BMAP‐27B effectively penetrated and cleared biofilms formed by virulent strains of Escherichia coli and Klebsiella pneumoniae.Mechanistic studies indicated that BMAP‐27B exerts its antibacterial activity by disrupting bacterial membranes and inhibiting bacterial energy metabolism.BMAP‐27B effectively enhances the efficacy of carbapenems against NDM‐positive isolates by inhibiting efflux pump activity and chelating Zn^(2+) to inhibit NDM proteases,thus reversing carbapenem resistance in NDM‐CRE.Importantly,BMAP‐27B maintained excellent antimicrobial stability under extreme pH changes and high salt concentrations,along with resistance to serum and protease degradation.Investigations revealed that BMAP‐27B also shows ideal biocompatibility and therapeutic efficacy in vivo.In summary,the highly potent antibacterial activity of BMAP‐27B,along with its potential role as a broadspectrum antibiotic adjuvant,makes it a promising candidate for combating infections caused by foodborne NDM‐CRE and preventing pathogen transmission at the animal‐human‐environment interface.
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 National Key Research and Development Program of China(2024YFE0199000)the National Natural Science Foundation of China(82000011)+1 种基金Hainan Provincial Natural Science Foundation of China(825RC764)the Decision-Making Consultation Project of Shanghai Jiao Tong University(JCZXSJB2023-13).
文摘Introduction:Carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a significant global public health threat.The dissemination of resistance is accelerated by plasmids harboring multiple carbapenemase genes,posing a particular challenge to the limited treatment options,including ceftazidimeavibactam.Methods:In this study,a CRKP strain,KpBSI024,was isolated from a patient with bloodstream infection in the intensive care unit of a tertiary hospital in China.The whole-genome sequencing combined with bioinformatic analysis was used to investigate the structural features of plasmids and associated resistance genes.In addition,conjugation experiments were conducted to assess the transferability of the resistance plasmid.Results:KpBSI024 exhibited resistance to carbapenems and ceftazidime-avibactam and was identified as sequence type ST1514.Whole-genome sequencing revealed that two carbapenemase genes,bla_(KPC-2) and bla_(IMP-4),coexisted on a 53 kb IncP6-type plasmid.This plasmid exhibited a complex structure,likely formed through multiple recombination events mediated by IS26 between plasmids of different Inc types.Although the resistance plasmid encodes a type IV secretion system,it lacks a relaxase gene and is therefore non-self-transmissible;however,it could be transferred at low frequency to Escherichia coli with the assistance of a conjugative plasmid.The growth of the transconjugants was not affected by the acquisition of the resistance plasmid,and they displayed resistance profiles to carbapenems and ceftazidime-avibactam similar to the donor strain.Conclusions:The coexistence of bla_(KPC-2) and bla_(IMP-4) on an IncP-type plasmid in a clinical K.pneumoniae isolate highlights the critical role of recombination events in the dissemination of resistance genes.The emergence of such multidrug-resistant plasmids underscores the urgent need for genomic surveillance and the development of innovative antimicrobial strategies to control the spread of highrisk resistance plasmids.
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 bla_(NDM) 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).
