Emergence of multiple carbapenemase-producing organisms in single patients: an increasing threat to treatment of infection

Emergence of multiple carbapenemase-producing organisms in single patients: an increasing threat... Sir, The global spread of carbapenemase-producing organisms (CPOs) poses a growing threat to health services worldwide. The coexistence of various CPOs in single patients has been reported.1–4 Recently, a study was conducted on a hospitalized patient from whom five CPOs were identified. The patient was a male in his 80s and he was admitted to the respiratory ICU (RICU) with lung and urinary tract infections in autumn 2014 and died 10 months later. While in the RICU he received multiple antibiotics, including piperacillin/tazobactam, ceftazidime, minocycline, moxifloxacin, meropenem and imipenem. This study did not require formal ethical approval, because we have only analysed the characteristics of clinical isolates that were collected during routine bacteriological analyses and no human participants were involved in this study. All data were anonymously analysed. All clinical isolates were identified by VITEK® MS (bioMérieux SA, Marcy-l’Étoile, France). The MICs of commonly used antimicrobial agents (listed in Table 1) were determined by Etest (AB bioMérieux, Solna, Sweden). The modified Hodge test was performed to detect carbapenemase producers for the isolates that exhibited non-susceptibility to carbapenems. These isolates were also screened for common carbapenemase genes by multiplex PCR amplification and subsequent amplicon sequencing. Clinical isolates that exhibited non-susceptibility to carbapenems in combination with either positive modified Hodge test results or positive PCR results were identified as CPOs. PFGE was performed to analyse the genetic relatedness of CPOs. The size and incompatibility types of blaOXA-48-carrying plasmids were analysed by S1-PFGE, Southern blotting and multiple PCR. Table 1 Characteristics of carbapenemase-producing Gram-negative organisms from the same patient Isolate no.  Species  Source  Isolation date (dd/mm/yyyy)  PFGE type  Carbapenemase(s)  MIC (mg/L)   CTX  CAZ  FEP  TZP  IPM  MEM  ETP  AMK  CIP  IRA001  A. baumannii  sputum  18/10/2014  ABA1  OXA-23, OXA-51  >64  >64  >64  >128  >16  >16  >8  >64  >4  IRP001  P. aeruginosa  sputum  05/11/2014  PAE1  VIM-1  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR1247  K. pneumoniae  urine  04/02/2015  X  KPC-2, OXA-48  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR5690  K. pneumoniae  urine  04/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5691  K. pneumoniae  sputum  19/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5692  K. pneumoniae  sputum  22/07/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5693  K. pneumoniae  sputum  25/08/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR53017  E. coli  urine  01/07/2015  E  OXA-48  >64  16  >64  64  <1  <1  >8  >64  >4  IR5283  E. cloacae  sputum  21/08/2015  N/A  OXA-48  >64  4  16  64  8  4  4  >64  >4  Isolate no.  Species  Source  Isolation date (dd/mm/yyyy)  PFGE type  Carbapenemase(s)  MIC (mg/L)   CTX  CAZ  FEP  TZP  IPM  MEM  ETP  AMK  CIP  IRA001  A. baumannii  sputum  18/10/2014  ABA1  OXA-23, OXA-51  >64  >64  >64  >128  >16  >16  >8  >64  >4  IRP001  P. aeruginosa  sputum  05/11/2014  PAE1  VIM-1  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR1247  K. pneumoniae  urine  04/02/2015  X  KPC-2, OXA-48  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR5690  K. pneumoniae  urine  04/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5691  K. pneumoniae  sputum  19/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5692  K. pneumoniae  sputum  22/07/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5693  K. pneumoniae  sputum  25/08/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR53017  E. coli  urine  01/07/2015  E  OXA-48  >64  16  >64  64  <1  <1  >8  >64  >4  IR5283  E. cloacae  sputum  21/08/2015  N/A  OXA-48  >64  4  16  64  8  4  4  >64  >4  CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; TZP, piperacillin/tazobactam; IPM, imipenem; MEM, meropenem; ETP, ertapenem; AMK, amikacin; CIP, ciprofloxacin; N/A, not applicable. In total, five species of CPO were isolated from sputum and urine samples from the patient, including OXA-23- and OXA-51-producing Acinetobacter baumannii, VIM-1-producing Pseudomonas aeruginosa, KPC-2- and OXA-48-producing Klebsiella pneumoniae, OXA-48-producing Escherichia coli and OXA-48-producing Enterobacter cloacae (Table 1 and Figure 1). PFGE results revealed that the 14 A. baumannii isolates belonged to the same clone (ABA1), and the 9 P. aeruginosa also belonged to the same clone (PAE1). The A. baumannii ABA1 and P. aeruginosa PAE1 were persistent in sputum specimens during the hospitalization (Figure 1). Meanwhile, OXA-48-producing K. pneumoniae clone A was isolated from his sputum and urine during the last 3 months of his hospitalization. During this same period, OXA-48-producing E. coli and E. cloacae were also identified (Figure 1). Plasmid analysis revealed that the OXA-48-producing K. pneumoniae, E. coli and E. cloacae had the same ∼60 kb IncL/M blaOXA-48-carrying plasmid. In addition, blaKPC-2 was found to coexist in OXA-48-producing K. pneumoniae IR1247, which had no genetic relatedness to OXA-48-producing type A K. pneumoniae (Table 1). Figure 1 View largeDownload slide Time of isolation and duration of carriage of CPOs. The x-axis indicates the patient’s stay in hospital broken down by month. The numbers of different CPOs are indicated on the y-axis. IRA001, A. baumannii producing OXA-23 and OXA-51; IRP001, P. aeruginosa producing VIM-1; IR1247, K. pneumoniae producing KPC-2 and OXA-48; IR5690, K. pneumoniae producing OXA-48 (PFGE type A); IR53017, E. coli producing OXA-48; IR5283, E. cloacae producing OXA-48. The black and grey shading indicate isolation of CPOs from sputum and urine samples, respectively. Figure 1 View largeDownload slide Time of isolation and duration of carriage of CPOs. The x-axis indicates the patient’s stay in hospital broken down by month. The numbers of different CPOs are indicated on the y-axis. IRA001, A. baumannii producing OXA-23 and OXA-51; IRP001, P. aeruginosa producing VIM-1; IR1247, K. pneumoniae producing KPC-2 and OXA-48; IR5690, K. pneumoniae producing OXA-48 (PFGE type A); IR53017, E. coli producing OXA-48; IR5283, E. cloacae producing OXA-48. The black and grey shading indicate isolation of CPOs from sputum and urine samples, respectively. Our hospital is one of the largest tertiary hospitals in China, with about 4000 beds. In our hospital, common carbapenemases such as KPC, OXA-48 and NDM have been widespread in Enterobacteriaceae.5–7 Our previous study confirmed that an E. coli isolate acquired a carbapenem resistance phenotype by acquiring a blaNDM-1-carrying plasmid in vivo.7 In this study, the OXA-48-producing K. pneumoniae clone A, which caused a nosocomial outbreak in the RICU of our hospital,5 was persistent in sputum specimens of the patient. This patient acquired the K. pneumoniae clone in hospital and was part of the outbreak. Then, OXA-48-producing E. coli and E. cloacae, which have not been detected in China, were isolated from urine and sputum one after the other (Table 1 and Figure 1). All OXA-48-producing enterobacterial species carried blaOXA-48-coding plasmids of the same size and incompatibility type (∼60 kb, IncL/M). Therefore, the E. coli and E. cloacae may have acquired the blaOXA-48-carrying plasmid in vivo from the OXA-48-producing K. pneumoniae and then exhibited the carbapenem resistance phenotype. These phenomena indicated the active transfer of drug resistance plasmids and their important role in mediating carbapenem resistance. The coexistence of KPC and other carbapenemases in K. pneumoniae has been reported worldwide, such as with IMP, VIM and NDM.8–10 In this study, K. pneumoniae co-producing KPC and OXA-48 was identified, which, to the best of our knowledge, has not been previously reported, indicating the strong ability of K. pneumoniae to integrate exogenous resistance genes. Furthermore, five CPOs were isolated from the patient. Although the coexistence of various CPOs in single patients has been reported worldwide,1–4 to the best of our knowledge, this is the first time five species of CPO have been isolated from the same patient. The diverse combinations of various carbapenemases co-harboured in K. pneumoniae and the increasing number of multiple CPOs coexisting in the same patient present an alarming trend in the development of bacterial resistance and will create a lot of difficulties in hospital infection control and public health. In this study, multiple CPOs have been identified in a single patient. The patient acquired the OXA-48-producing strain of K. pneumoniae during an outbreak in the hospital with likely subsequent transmission of the blaOXA-48 gene to other species. In addition, non-fermentative CPOs have also been recovered from this patient. Further research must be carried out to explore which patients tend to carry multiple CPOs and how to prevent the phenomenon from expanding. Funding This study was supported by the Special Key Project of Biosafety Technologies for the National Major Research & Development Program of China (2017YFC1200800). Transparency declarations None to declare. References 1 Tijet N, Richardson D, MacMullin G et al.   Characterization of multiple NDM-1-producing Enterobacteriaceae isolates from the same patient. Antimicrob Agents Chemother  2015; 59: 3648– 51. Google Scholar CrossRef Search ADS PubMed  2 Ding B, Hu F, Yang Y et al.   Four carbapenem-resistant Gram-negative species carrying distinct carbapenemases in a single patient. J Clin Microbiol  2015; 53: 1031– 3. Google Scholar CrossRef Search ADS PubMed  3 Huang YM, Zhong LL, Zhang XF et al.   NDM-1-producing Citrobacter freundii, Escherichia coli, and Acinetobacter baumannii identified from a single patient in China. Antimicrob Agents Chemother  2015; 59: 5073– 7. Google Scholar CrossRef Search ADS PubMed  4 Yu F, Wang S, Lv J et al.   Coexistence of OXA-48-producing Klebsiella pneumoniae and Escherichia coli in a hospitalized patient who returned from Europe to China. Antimicrob Agents Chemother  2017; 61: e02580–16. Google Scholar CrossRef Search ADS PubMed  5 Guo L, An J, Ma Y et al.   Nosocomial outbreak of OXA-48-producing Klebsiella pneumoniae in a Chinese hospital: clonal transmission of ST147 and ST383. PLoS One  2016; 11: e0160754. Google Scholar CrossRef Search ADS PubMed  6 Yang J, Ye L, Guo L et al.   A nosocomial outbreak of KPC-2-producing Klebsiella pneumoniae in a Chinese hospital: dissemination of ST11 and emergence of ST37, ST392 and ST395. Clin Microbiol Infect  2013; 19: E509– 15. Google Scholar CrossRef Search ADS PubMed  7 An J, Guo L, Zhou L et al.   NDM-producing Enterobacteriaceae in a Chinese hospital, 2014–2015: identification of NDM-producing Citrobacter werkmanii and acquisition of blaNDM-1-carrying plasmid in vivo in a clinical Escherichia coli isolate. J Med Microbiol  2016; 65: 1253– 9. Google Scholar CrossRef Search ADS PubMed  8 Wang Y, Cao W, Zhu X et al.   Characterization of a novel Klebsiella pneumoniae sequence type 476 carrying both blaKPC-2 and blaIMP-4. Eur J Clin Microbiol Infect Dis  2012; 31: 1867– 72. Google Scholar CrossRef Search ADS PubMed  9 Steinmann J, Kaase M, Gatermann S et al.   Outbreak due to a Klebsiella pneumoniae strain harbouring KPC-2 and VIM-1 in a German university hospital, July 2010 to January 2011. Euro Surveill  2011; 16: pii=19944. 10 Kumarasamy K, Kalyanasundaram A. Emergence of Klebsiella pneumoniae isolate co-producing NDM-1 with KPC-2 from India. J Antimicrob Chemother  2012; 67: 243– 4. Google Scholar CrossRef Search ADS PubMed  © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Antimicrobial Chemotherapy Oxford University Press

Emergence of multiple carbapenemase-producing organisms in single patients: an increasing threat to treatment of infection

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© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Abstract

Sir, The global spread of carbapenemase-producing organisms (CPOs) poses a growing threat to health services worldwide. The coexistence of various CPOs in single patients has been reported.1–4 Recently, a study was conducted on a hospitalized patient from whom five CPOs were identified. The patient was a male in his 80s and he was admitted to the respiratory ICU (RICU) with lung and urinary tract infections in autumn 2014 and died 10 months later. While in the RICU he received multiple antibiotics, including piperacillin/tazobactam, ceftazidime, minocycline, moxifloxacin, meropenem and imipenem. This study did not require formal ethical approval, because we have only analysed the characteristics of clinical isolates that were collected during routine bacteriological analyses and no human participants were involved in this study. All data were anonymously analysed. All clinical isolates were identified by VITEK® MS (bioMérieux SA, Marcy-l’Étoile, France). The MICs of commonly used antimicrobial agents (listed in Table 1) were determined by Etest (AB bioMérieux, Solna, Sweden). The modified Hodge test was performed to detect carbapenemase producers for the isolates that exhibited non-susceptibility to carbapenems. These isolates were also screened for common carbapenemase genes by multiplex PCR amplification and subsequent amplicon sequencing. Clinical isolates that exhibited non-susceptibility to carbapenems in combination with either positive modified Hodge test results or positive PCR results were identified as CPOs. PFGE was performed to analyse the genetic relatedness of CPOs. The size and incompatibility types of blaOXA-48-carrying plasmids were analysed by S1-PFGE, Southern blotting and multiple PCR. Table 1 Characteristics of carbapenemase-producing Gram-negative organisms from the same patient Isolate no.  Species  Source  Isolation date (dd/mm/yyyy)  PFGE type  Carbapenemase(s)  MIC (mg/L)   CTX  CAZ  FEP  TZP  IPM  MEM  ETP  AMK  CIP  IRA001  A. baumannii  sputum  18/10/2014  ABA1  OXA-23, OXA-51  >64  >64  >64  >128  >16  >16  >8  >64  >4  IRP001  P. aeruginosa  sputum  05/11/2014  PAE1  VIM-1  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR1247  K. pneumoniae  urine  04/02/2015  X  KPC-2, OXA-48  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR5690  K. pneumoniae  urine  04/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5691  K. pneumoniae  sputum  19/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5692  K. pneumoniae  sputum  22/07/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5693  K. pneumoniae  sputum  25/08/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR53017  E. coli  urine  01/07/2015  E  OXA-48  >64  16  >64  64  <1  <1  >8  >64  >4  IR5283  E. cloacae  sputum  21/08/2015  N/A  OXA-48  >64  4  16  64  8  4  4  >64  >4  Isolate no.  Species  Source  Isolation date (dd/mm/yyyy)  PFGE type  Carbapenemase(s)  MIC (mg/L)   CTX  CAZ  FEP  TZP  IPM  MEM  ETP  AMK  CIP  IRA001  A. baumannii  sputum  18/10/2014  ABA1  OXA-23, OXA-51  >64  >64  >64  >128  >16  >16  >8  >64  >4  IRP001  P. aeruginosa  sputum  05/11/2014  PAE1  VIM-1  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR1247  K. pneumoniae  urine  04/02/2015  X  KPC-2, OXA-48  >64  >64  >64  >128  >16  >16  >8  >64  >4  IR5690  K. pneumoniae  urine  04/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5691  K. pneumoniae  sputum  19/06/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5692  K. pneumoniae  sputum  22/07/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR5693  K. pneumoniae  sputum  25/08/2015  A  OXA-48  >64  4  2  >128  2  2  >8  >64  >4  IR53017  E. coli  urine  01/07/2015  E  OXA-48  >64  16  >64  64  <1  <1  >8  >64  >4  IR5283  E. cloacae  sputum  21/08/2015  N/A  OXA-48  >64  4  16  64  8  4  4  >64  >4  CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; TZP, piperacillin/tazobactam; IPM, imipenem; MEM, meropenem; ETP, ertapenem; AMK, amikacin; CIP, ciprofloxacin; N/A, not applicable. In total, five species of CPO were isolated from sputum and urine samples from the patient, including OXA-23- and OXA-51-producing Acinetobacter baumannii, VIM-1-producing Pseudomonas aeruginosa, KPC-2- and OXA-48-producing Klebsiella pneumoniae, OXA-48-producing Escherichia coli and OXA-48-producing Enterobacter cloacae (Table 1 and Figure 1). PFGE results revealed that the 14 A. baumannii isolates belonged to the same clone (ABA1), and the 9 P. aeruginosa also belonged to the same clone (PAE1). The A. baumannii ABA1 and P. aeruginosa PAE1 were persistent in sputum specimens during the hospitalization (Figure 1). Meanwhile, OXA-48-producing K. pneumoniae clone A was isolated from his sputum and urine during the last 3 months of his hospitalization. During this same period, OXA-48-producing E. coli and E. cloacae were also identified (Figure 1). Plasmid analysis revealed that the OXA-48-producing K. pneumoniae, E. coli and E. cloacae had the same ∼60 kb IncL/M blaOXA-48-carrying plasmid. In addition, blaKPC-2 was found to coexist in OXA-48-producing K. pneumoniae IR1247, which had no genetic relatedness to OXA-48-producing type A K. pneumoniae (Table 1). Figure 1 View largeDownload slide Time of isolation and duration of carriage of CPOs. The x-axis indicates the patient’s stay in hospital broken down by month. The numbers of different CPOs are indicated on the y-axis. IRA001, A. baumannii producing OXA-23 and OXA-51; IRP001, P. aeruginosa producing VIM-1; IR1247, K. pneumoniae producing KPC-2 and OXA-48; IR5690, K. pneumoniae producing OXA-48 (PFGE type A); IR53017, E. coli producing OXA-48; IR5283, E. cloacae producing OXA-48. The black and grey shading indicate isolation of CPOs from sputum and urine samples, respectively. Figure 1 View largeDownload slide Time of isolation and duration of carriage of CPOs. The x-axis indicates the patient’s stay in hospital broken down by month. The numbers of different CPOs are indicated on the y-axis. IRA001, A. baumannii producing OXA-23 and OXA-51; IRP001, P. aeruginosa producing VIM-1; IR1247, K. pneumoniae producing KPC-2 and OXA-48; IR5690, K. pneumoniae producing OXA-48 (PFGE type A); IR53017, E. coli producing OXA-48; IR5283, E. cloacae producing OXA-48. The black and grey shading indicate isolation of CPOs from sputum and urine samples, respectively. Our hospital is one of the largest tertiary hospitals in China, with about 4000 beds. In our hospital, common carbapenemases such as KPC, OXA-48 and NDM have been widespread in Enterobacteriaceae.5–7 Our previous study confirmed that an E. coli isolate acquired a carbapenem resistance phenotype by acquiring a blaNDM-1-carrying plasmid in vivo.7 In this study, the OXA-48-producing K. pneumoniae clone A, which caused a nosocomial outbreak in the RICU of our hospital,5 was persistent in sputum specimens of the patient. This patient acquired the K. pneumoniae clone in hospital and was part of the outbreak. Then, OXA-48-producing E. coli and E. cloacae, which have not been detected in China, were isolated from urine and sputum one after the other (Table 1 and Figure 1). All OXA-48-producing enterobacterial species carried blaOXA-48-coding plasmids of the same size and incompatibility type (∼60 kb, IncL/M). Therefore, the E. coli and E. cloacae may have acquired the blaOXA-48-carrying plasmid in vivo from the OXA-48-producing K. pneumoniae and then exhibited the carbapenem resistance phenotype. These phenomena indicated the active transfer of drug resistance plasmids and their important role in mediating carbapenem resistance. The coexistence of KPC and other carbapenemases in K. pneumoniae has been reported worldwide, such as with IMP, VIM and NDM.8–10 In this study, K. pneumoniae co-producing KPC and OXA-48 was identified, which, to the best of our knowledge, has not been previously reported, indicating the strong ability of K. pneumoniae to integrate exogenous resistance genes. Furthermore, five CPOs were isolated from the patient. Although the coexistence of various CPOs in single patients has been reported worldwide,1–4 to the best of our knowledge, this is the first time five species of CPO have been isolated from the same patient. The diverse combinations of various carbapenemases co-harboured in K. pneumoniae and the increasing number of multiple CPOs coexisting in the same patient present an alarming trend in the development of bacterial resistance and will create a lot of difficulties in hospital infection control and public health. In this study, multiple CPOs have been identified in a single patient. The patient acquired the OXA-48-producing strain of K. pneumoniae during an outbreak in the hospital with likely subsequent transmission of the blaOXA-48 gene to other species. In addition, non-fermentative CPOs have also been recovered from this patient. Further research must be carried out to explore which patients tend to carry multiple CPOs and how to prevent the phenomenon from expanding. Funding This study was supported by the Special Key Project of Biosafety Technologies for the National Major Research & Development Program of China (2017YFC1200800). Transparency declarations None to declare. References 1 Tijet N, Richardson D, MacMullin G et al.   Characterization of multiple NDM-1-producing Enterobacteriaceae isolates from the same patient. Antimicrob Agents Chemother  2015; 59: 3648– 51. Google Scholar CrossRef Search ADS PubMed  2 Ding B, Hu F, Yang Y et al.   Four carbapenem-resistant Gram-negative species carrying distinct carbapenemases in a single patient. J Clin Microbiol  2015; 53: 1031– 3. Google Scholar CrossRef Search ADS PubMed  3 Huang YM, Zhong LL, Zhang XF et al.   NDM-1-producing Citrobacter freundii, Escherichia coli, and Acinetobacter baumannii identified from a single patient in China. Antimicrob Agents Chemother  2015; 59: 5073– 7. Google Scholar CrossRef Search ADS PubMed  4 Yu F, Wang S, Lv J et al.   Coexistence of OXA-48-producing Klebsiella pneumoniae and Escherichia coli in a hospitalized patient who returned from Europe to China. Antimicrob Agents Chemother  2017; 61: e02580–16. Google Scholar CrossRef Search ADS PubMed  5 Guo L, An J, Ma Y et al.   Nosocomial outbreak of OXA-48-producing Klebsiella pneumoniae in a Chinese hospital: clonal transmission of ST147 and ST383. PLoS One  2016; 11: e0160754. Google Scholar CrossRef Search ADS PubMed  6 Yang J, Ye L, Guo L et al.   A nosocomial outbreak of KPC-2-producing Klebsiella pneumoniae in a Chinese hospital: dissemination of ST11 and emergence of ST37, ST392 and ST395. Clin Microbiol Infect  2013; 19: E509– 15. Google Scholar CrossRef Search ADS PubMed  7 An J, Guo L, Zhou L et al.   NDM-producing Enterobacteriaceae in a Chinese hospital, 2014–2015: identification of NDM-producing Citrobacter werkmanii and acquisition of blaNDM-1-carrying plasmid in vivo in a clinical Escherichia coli isolate. J Med Microbiol  2016; 65: 1253– 9. Google Scholar CrossRef Search ADS PubMed  8 Wang Y, Cao W, Zhu X et al.   Characterization of a novel Klebsiella pneumoniae sequence type 476 carrying both blaKPC-2 and blaIMP-4. Eur J Clin Microbiol Infect Dis  2012; 31: 1867– 72. Google Scholar CrossRef Search ADS PubMed  9 Steinmann J, Kaase M, Gatermann S et al.   Outbreak due to a Klebsiella pneumoniae strain harbouring KPC-2 and VIM-1 in a German university hospital, July 2010 to January 2011. Euro Surveill  2011; 16: pii=19944. 10 Kumarasamy K, Kalyanasundaram A. Emergence of Klebsiella pneumoniae isolate co-producing NDM-1 with KPC-2 from India. J Antimicrob Chemother  2012; 67: 243– 4. Google Scholar CrossRef Search ADS PubMed  © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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Journal of Antimicrobial ChemotherapyOxford University Press

Published: Feb 1, 2018

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