Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins ...Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.展开更多
Objective To characterize carbapenem (CPM)-non-susceptible Klebsiella pneumoniae (K. pneumoniae) and carbape-nemase produced by these strains isolated from Beijing Children's Hospital based on a five-year surveil...Objective To characterize carbapenem (CPM)-non-susceptible Klebsiella pneumoniae (K. pneumoniae) and carbape-nemase produced by these strains isolated from Beijing Children's Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 (53.1%) strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 (96.8%) and 3 (3.2%) IMP-producing isolates, respectively. 65 (36.3%) strains carried the blaNDM_1 gene. 6 (3.4%) strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 (NDM-1) producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children's Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.展开更多
Aim: To identify, analyse and control the outbreak of Carbapenamase producing Klebsiella pneumoniae. Objectives: 1) To detect multidrug resistant K. pneumoniae at the earliest and isolate patients. 2) To find out the ...Aim: To identify, analyse and control the outbreak of Carbapenamase producing Klebsiella pneumoniae. Objectives: 1) To detect multidrug resistant K. pneumoniae at the earliest and isolate patients. 2) To find out the predisposing causes for the occurrence of this outbreak. 3) To break the chain of infection transmission. 4) To reduce the risk of Hospital acquired infections. Methods: This retrospective study along with the surveillance was conducted from January 2017 to March 2017 at HCG multispecialty cancer hospital, Bangalore, India. Results: Total 15 patients were diagnosed with KPC infection during the first month of the study period. Those affected were mostly Male patients (73%), admitted in ICU (73%) for further treatment. In our study, the incidence of KPC infection was mostly found with bloodstream infections (60%), mostly seen in those with central lines (80%) followed by patients on ventilatory support (66%). Before the outbreak of KPC infection, all the patients (100%) had already been treated with higher antibiotics including Carbapenems. In our study, only nine out of fifteen patients (60%) could be salvaged with treatment and were discharged. Conclusions: Hospital Infection Control Committee’s regular screening and the training of healthcare professionals are vital for the control of the outbreak.展开更多
Background: Klebsiella pneumoniae is one of the most frequent opportunistic pathogens causing a range of infections and being resistant for beta-lactamases (ESBL) and Carbapenemases. Aim: The aim of the present study ...Background: Klebsiella pneumoniae is one of the most frequent opportunistic pathogens causing a range of infections and being resistant for beta-lactamases (ESBL) and Carbapenemases. Aim: The aim of the present study was to determine the antimicrobial resistance patterns and molecular characterization establishing the phenotypes and genotypes associated with drug resistance, an antibiogram of genotypically positive isolates for resistance of Klebsiella pneumoniae in clinical isolates at MRRH. Materials and Methods: A laboratory-based descriptive cross-sectional study that was conducted from September 2018 to May 2019 at MRRH. Klebsiella pneumoniae was identified by cultural and biochemical methods. Antibiotic sensitivity test was performed by modified Kirby-Bauer disc diffusion technique. ESBL production in Klebsiella pneumoniae was tested by double-disc synergy test, Carbapenemase production by MHT, Boronic Acid or EDTA test using Meropenem phenotypically and both resistance confirmed genotypically by Multiplex PCR. Results: Out of 1055 clinical isolates, 298 (28.2%) were found positive for Klebsiella.spp, 175 isolates were subcultured among which 22 (12.57%) were K. pneumoniae based on API 20E. Overall Sensitivity patterns of these Klebsiella pneumoniae isolates to Ceftriaxone, (Amoxicillin/Clavulanate), Gentamicin, Cefepime, Ciprofloxacin, Cefoxitin, Nitrofurantoin, Cefuroxime, piperacillin/tazobactam, Meropenem, Ceftazidime and cefotaxime were 72.7%, 63.7%, 54.5%, 45.5%, 31.8%, 31.8%, 27.3%, 27.3%, 22.7%, 22.7%, 18.2%, 9.1%, 9.1% respectively. ESBL producing K. pneumoniae was found at 68.18% (15/22) phenotypically. Genotypically;the ESBL genes were blaCTX-M (100%), blaSHV (80%) and blaTEM (100;47%);8/15 (73.3%) had CTX-M, SHV, TEM, 4/15 (26.67%) CTX-M, TEM, 3/15 (20.00%) CTX-M and SHV. Carbapenemase producing K. pneumoniae was found at 31.82% (7/22) phenotypically;1/7 (14.28%) by MHT, 4/7 (57.14%) Boronic acid test and 2/7 (28.58%) EDTA test. Genotypically;3/4 [(75%) 42.86%] had OXA-48, 1/4 [(25%) 14.28%] OXA-48 and KPC gene, 1/2 [(50%) 14.28%] KPC and VIM, 1/2 [(50%) 14.28%] KPC and KPC gene [(100%) 14.28%]. Conclusion/Recommendations: DDS to be used for ESBL production, MHT, Boronic Acid test and EDTA tests using Meropenem/or Imipenem for Carbapenemase-production routinely.展开更多
Background Carbapenems are used to treat severe infections caused by multi-drug-resistant organisms, however, the emergence of carbapenem-resistant bacterial isolates is becoming an increasing therapeutic challenge. S...Background Carbapenems are used to treat severe infections caused by multi-drug-resistant organisms, however, the emergence of carbapenem-resistant bacterial isolates is becoming an increasing therapeutic challenge. Since the first Klebsiella (K.) pneumoniae carbapenemase (KPC)-producing K. pneumoniae was reported in 2001, KPC-producing isolates have been found increasingly, specially in Enterobacteriaceae. The aim of this study was to characterize the mechanisms of a carbapenem-resistant Proteus (P.) mirabilis. Methods A carbapenem-resistant P. mirabilis isolate was recovered from pleural drainage fluid of a patient admitted to surgical intensive care unit. Antimicrobial susceptibility testing of the isolate was performed by disk diffusion according to Clinical and Laboratory Standards Institute guidelines, and subsequent minimal inhibitory concentrations were determined with the E-test. Amplification of the blaKPC gene generated a positive band and the PCR products were sequenced subsequently. The plasmid of the isolate was extracted and was successfully transformed into Escherichia (E.) coli DH5a. Results The P. mirabilis isolate was resistant to all detected antimicrobial agents except tigecycline. KPC-2 was confirmed by DNA sequence analysis. The transformant E. coil was resistant to carbapenems. Further study demonstrated that upstream and downstream regions of b/aKPC-2 were identical to that observed in K. pneumoniae submitted to GenBank from China in 2007. Conclusion Carbapenem resistance in the P. mirabilis isolate in this study is mainly due to production of KPC-2.展开更多
Background: Klebsiellapneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred fr...Background: Klebsiellapneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred from August 4, 2014, to March 17, 2015. The aim of this study was to analyze the epidemiology and molecular characteristics of the K. pneumoniae strains isolated during the outbreak. Methods: Nonduplicate carbapenem-resistant K. pneumoniae isolates were screened for blanc," and multiple other resistance determinants using polymerase chain reaction. Subsequent studies included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, analysis of plasmids, and genetic organization ofblaKPC-2 locus. Results: Seventeen blaKPC-2-positive K. pneumoniae were identified. A wide range of resistant determinants was detected. Most isolates (88.2%) coharbored blaKPC-2 and rmtB in addition to other resistance genes, including biaSHV-1, blaTEM-1, and aac(3)-lla. The blaKPC-2 and rmtB genes were located on the conjugative IncFIB-type plasmid. Genetic organization of blaKPC-2 locus in most strains was consistent with that of the plasmid pKP048. Four types (A l, A2, A3, and B) were detected by PFGE, and Type A1, an ST11, was the predominant PFGE type. A novel K. pneumoniae sequence type (ST1883) related to STI 1 was discovered. Conclusions: These isolates in our study appeared to be clonal and STI 1 K. pneumoniae was the predominant clone attributed to the outbreak. Coharbing of blaKPC-2 and rmtB, which were located on a transferable plasmid, in clinical K. pneumoniae isolates may lead to the emergence of a new pattern of drug resistance.展开更多
The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses serious threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive ge...The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses serious threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host–blaKPC-carrying plasmid(Clade 3.1+3.2–IncFIIpHN7A8,Clade 3.1+3.2–IncFIIpHN7A8:IncR,and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.展开更多
Background Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia (E.) coil has been reported in China since 2008.However,there is no information about the molecular epidemiology of KPC-producing E.coil i...Background Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia (E.) coil has been reported in China since 2008.However,there is no information about the molecular epidemiology of KPC-producing E.coil in China.In this study,we aimed to investigate the sequence type (ST) and characteristics of KPC-producing E.coil isolates in China.Methods Three carbapenem-resistant isolates of E.coil (E1,E2,and E3) from one teaching hospital in Hangzhou covering a one year period were analyzed.Antibiotic susceptibility was determined by Etest.Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used for epidemiological analysis.The genetic structure around blaKPC,the major plasmid incompatibility typing,and the identification of 3-lactamase gene types were performed by PCR and the positive products were subsequently sequenced.Plasmids were analyzed by transformation,restriction,and Southern blotting.Results PFGE demonstrated that patterns of isolates E1 and E2 were clonally-related and designated as patterns A1 and A2; pattern of isolate E3 was different and designated as pattern B.MLST analysis showed that the three isolates displayed one common sequence type ST131.The identification of bla gene types by PCR and sequencing showed that blaKPC-2,blaCTX-M-14,and blaTEM-1 were detected in all three isolates.All three isolates carried a KPC-2-encoding plasmid of the IncN replicon.Plasmid analysis and hybridization experiments showed that the isolates were found simultaneously to carry two or four plasmids.The blaKPc-2 gene in E1 and E2 was located in a plasmid with size of ca.50 kb.However,the blaKPC-2 gene in E3 was located in a plasmid with size of ca.130 kb.Conclusions E.coil ST131 with KPC-2 β-1actamase has emerged in China,which enlarges the geographical area where the ST131 KPC-oroducing E.coil strains have diffused.展开更多
基金supported by the National Natural Science Foundation of China(No.31771189)the Wuhan Health Commission(No.WX18C17 and No.WX19Q31)the Natural Science Foundation of Hubei Province,China(No.2017CFA065 and No.WJ2019H378).
文摘Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.
基金supported by Scientific Research Project of Beijing Children's Hospital(2012MS08)Beijing Municipal Science and Technology Project(D131100005313014)
文摘Objective To characterize carbapenem (CPM)-non-susceptible Klebsiella pneumoniae (K. pneumoniae) and carbape-nemase produced by these strains isolated from Beijing Children's Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 (53.1%) strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 (96.8%) and 3 (3.2%) IMP-producing isolates, respectively. 65 (36.3%) strains carried the blaNDM_1 gene. 6 (3.4%) strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 (NDM-1) producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children's Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.
文摘Aim: To identify, analyse and control the outbreak of Carbapenamase producing Klebsiella pneumoniae. Objectives: 1) To detect multidrug resistant K. pneumoniae at the earliest and isolate patients. 2) To find out the predisposing causes for the occurrence of this outbreak. 3) To break the chain of infection transmission. 4) To reduce the risk of Hospital acquired infections. Methods: This retrospective study along with the surveillance was conducted from January 2017 to March 2017 at HCG multispecialty cancer hospital, Bangalore, India. Results: Total 15 patients were diagnosed with KPC infection during the first month of the study period. Those affected were mostly Male patients (73%), admitted in ICU (73%) for further treatment. In our study, the incidence of KPC infection was mostly found with bloodstream infections (60%), mostly seen in those with central lines (80%) followed by patients on ventilatory support (66%). Before the outbreak of KPC infection, all the patients (100%) had already been treated with higher antibiotics including Carbapenems. In our study, only nine out of fifteen patients (60%) could be salvaged with treatment and were discharged. Conclusions: Hospital Infection Control Committee’s regular screening and the training of healthcare professionals are vital for the control of the outbreak.
文摘Background: Klebsiella pneumoniae is one of the most frequent opportunistic pathogens causing a range of infections and being resistant for beta-lactamases (ESBL) and Carbapenemases. Aim: The aim of the present study was to determine the antimicrobial resistance patterns and molecular characterization establishing the phenotypes and genotypes associated with drug resistance, an antibiogram of genotypically positive isolates for resistance of Klebsiella pneumoniae in clinical isolates at MRRH. Materials and Methods: A laboratory-based descriptive cross-sectional study that was conducted from September 2018 to May 2019 at MRRH. Klebsiella pneumoniae was identified by cultural and biochemical methods. Antibiotic sensitivity test was performed by modified Kirby-Bauer disc diffusion technique. ESBL production in Klebsiella pneumoniae was tested by double-disc synergy test, Carbapenemase production by MHT, Boronic Acid or EDTA test using Meropenem phenotypically and both resistance confirmed genotypically by Multiplex PCR. Results: Out of 1055 clinical isolates, 298 (28.2%) were found positive for Klebsiella.spp, 175 isolates were subcultured among which 22 (12.57%) were K. pneumoniae based on API 20E. Overall Sensitivity patterns of these Klebsiella pneumoniae isolates to Ceftriaxone, (Amoxicillin/Clavulanate), Gentamicin, Cefepime, Ciprofloxacin, Cefoxitin, Nitrofurantoin, Cefuroxime, piperacillin/tazobactam, Meropenem, Ceftazidime and cefotaxime were 72.7%, 63.7%, 54.5%, 45.5%, 31.8%, 31.8%, 27.3%, 27.3%, 22.7%, 22.7%, 18.2%, 9.1%, 9.1% respectively. ESBL producing K. pneumoniae was found at 68.18% (15/22) phenotypically. Genotypically;the ESBL genes were blaCTX-M (100%), blaSHV (80%) and blaTEM (100;47%);8/15 (73.3%) had CTX-M, SHV, TEM, 4/15 (26.67%) CTX-M, TEM, 3/15 (20.00%) CTX-M and SHV. Carbapenemase producing K. pneumoniae was found at 31.82% (7/22) phenotypically;1/7 (14.28%) by MHT, 4/7 (57.14%) Boronic acid test and 2/7 (28.58%) EDTA test. Genotypically;3/4 [(75%) 42.86%] had OXA-48, 1/4 [(25%) 14.28%] OXA-48 and KPC gene, 1/2 [(50%) 14.28%] KPC and VIM, 1/2 [(50%) 14.28%] KPC and KPC gene [(100%) 14.28%]. Conclusion/Recommendations: DDS to be used for ESBL production, MHT, Boronic Acid test and EDTA tests using Meropenem/or Imipenem for Carbapenemase-production routinely.
文摘Background Carbapenems are used to treat severe infections caused by multi-drug-resistant organisms, however, the emergence of carbapenem-resistant bacterial isolates is becoming an increasing therapeutic challenge. Since the first Klebsiella (K.) pneumoniae carbapenemase (KPC)-producing K. pneumoniae was reported in 2001, KPC-producing isolates have been found increasingly, specially in Enterobacteriaceae. The aim of this study was to characterize the mechanisms of a carbapenem-resistant Proteus (P.) mirabilis. Methods A carbapenem-resistant P. mirabilis isolate was recovered from pleural drainage fluid of a patient admitted to surgical intensive care unit. Antimicrobial susceptibility testing of the isolate was performed by disk diffusion according to Clinical and Laboratory Standards Institute guidelines, and subsequent minimal inhibitory concentrations were determined with the E-test. Amplification of the blaKPC gene generated a positive band and the PCR products were sequenced subsequently. The plasmid of the isolate was extracted and was successfully transformed into Escherichia (E.) coli DH5a. Results The P. mirabilis isolate was resistant to all detected antimicrobial agents except tigecycline. KPC-2 was confirmed by DNA sequence analysis. The transformant E. coil was resistant to carbapenems. Further study demonstrated that upstream and downstream regions of b/aKPC-2 were identical to that observed in K. pneumoniae submitted to GenBank from China in 2007. Conclusion Carbapenem resistance in the P. mirabilis isolate in this study is mainly due to production of KPC-2.
基金grants from Hunan Development and Reform Investment from the Development and Reform Commission of the Hunan Province,the Natural Science Foundation of the Hunan Province
文摘Background: Klebsiellapneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred from August 4, 2014, to March 17, 2015. The aim of this study was to analyze the epidemiology and molecular characteristics of the K. pneumoniae strains isolated during the outbreak. Methods: Nonduplicate carbapenem-resistant K. pneumoniae isolates were screened for blanc," and multiple other resistance determinants using polymerase chain reaction. Subsequent studies included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, analysis of plasmids, and genetic organization ofblaKPC-2 locus. Results: Seventeen blaKPC-2-positive K. pneumoniae were identified. A wide range of resistant determinants was detected. Most isolates (88.2%) coharbored blaKPC-2 and rmtB in addition to other resistance genes, including biaSHV-1, blaTEM-1, and aac(3)-lla. The blaKPC-2 and rmtB genes were located on the conjugative IncFIB-type plasmid. Genetic organization of blaKPC-2 locus in most strains was consistent with that of the plasmid pKP048. Four types (A l, A2, A3, and B) were detected by PFGE, and Type A1, an ST11, was the predominant PFGE type. A novel K. pneumoniae sequence type (ST1883) related to STI 1 was discovered. Conclusions: These isolates in our study appeared to be clonal and STI 1 K. pneumoniae was the predominant clone attributed to the outbreak. Coharbing of blaKPC-2 and rmtB, which were located on a transferable plasmid, in clinical K. pneumoniae isolates may lead to the emergence of a new pattern of drug resistance.
基金supported by the National Natural Science Foundation of China(Grant No.31770870)the National Science and Technology Major Projects of China(Grant No.2018ZX10302-301-004-003).
文摘The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses serious threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host–blaKPC-carrying plasmid(Clade 3.1+3.2–IncFIIpHN7A8,Clade 3.1+3.2–IncFIIpHN7A8:IncR,and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.
基金This study was supported by the grants from the National Natural Science Foundation of China (No.81171615) and the Natural Science Foundation of Zhejiang Province (No.Y2100355).
文摘Background Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia (E.) coil has been reported in China since 2008.However,there is no information about the molecular epidemiology of KPC-producing E.coil in China.In this study,we aimed to investigate the sequence type (ST) and characteristics of KPC-producing E.coil isolates in China.Methods Three carbapenem-resistant isolates of E.coil (E1,E2,and E3) from one teaching hospital in Hangzhou covering a one year period were analyzed.Antibiotic susceptibility was determined by Etest.Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used for epidemiological analysis.The genetic structure around blaKPC,the major plasmid incompatibility typing,and the identification of 3-lactamase gene types were performed by PCR and the positive products were subsequently sequenced.Plasmids were analyzed by transformation,restriction,and Southern blotting.Results PFGE demonstrated that patterns of isolates E1 and E2 were clonally-related and designated as patterns A1 and A2; pattern of isolate E3 was different and designated as pattern B.MLST analysis showed that the three isolates displayed one common sequence type ST131.The identification of bla gene types by PCR and sequencing showed that blaKPC-2,blaCTX-M-14,and blaTEM-1 were detected in all three isolates.All three isolates carried a KPC-2-encoding plasmid of the IncN replicon.Plasmid analysis and hybridization experiments showed that the isolates were found simultaneously to carry two or four plasmids.The blaKPc-2 gene in E1 and E2 was located in a plasmid with size of ca.50 kb.However,the blaKPC-2 gene in E3 was located in a plasmid with size of ca.130 kb.Conclusions E.coil ST131 with KPC-2 β-1actamase has emerged in China,which enlarges the geographical area where the ST131 KPC-oroducing E.coil strains have diffused.