Frontiers of Medicine

, Volume 12, Issue 2, pp 182–188 | Cite as

Prevalence and drug resistance characteristics of carbapenem-resistant Enterobacteriaceae in Hangzhou, China

  • Yan Yang
  • Jian Chen
  • Di Lin
  • Xujian Xu
  • Jun Cheng
  • Changgui Sun
Research Article


With the abuse of antimicrobial agents in developing countries, increasing number of carbapenem-resistant Enterobacteriaceae (CRE) attracted considerable public concern. A retrospective study was conducted based on 242 CRE strains from a tertiary hospital in Hangzhou, China to investigate prevalence and drug resistance characteristics of CRE in southeast China. Bacterial species were identified. Antimicrobial susceptibility was examined by broth microdilution method or epsilometer test. Resistant β-lactamase genes were identified by polymerase chain reaction and sequencing. Genotypes were investigated by phylogenetic analysis. Klebsiella pneumoniae and Escherichia coli were the most prevalent types of species, with occurrence in 71.9% and 21.9% of the strains, respectively. All strains exhibited high resistance (> 70%) against β-lactam antibiotics, ciprofloxacin, trimethoprim–sulfamethoxazole, and nitrofurantoin but exhibited low resistance against tigecycline (0.8%) and minocycline (8.3%). A total of 123 strains harbored more than two kinds of β-lactamase genes. blaKPC-2, blaSHV-11, blaTEM-1, and blaCTX-M-14 were the predominant genotypes, with detection rates of 60.3%, 61.6%, 43.4%, and 16.5%, respectively, and were highly identical with reference sequences in different countries, indicating potential horizontal dissemination. IMP-4 was the most frequent class B metallo-lactamases in this study. In conclusion, continuous surveillance and effective prevention should be emphasized to reduce spread of CRE.


Enterobacteriaceae carbapenem β-lactamase genes phylogenetic analysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This work was supported by a grant from the Medical Science Foundation of Nanjing Military Command (No. 10Z037). The authors are grateful to Prof. A.A. Medeiros (The Miriam Hospital, Providence, RI, USA) for the Enterobacter cloacae IMI-1 strain, Prof. G. A. Jacoby (Massachusetts General Hospital, Boston, MA, USA) for the Klebsiella pneumoniae IMP-4 strain, and Prof. Rong Zhang (Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China) for the Klebsiella pneumoniae KPC-2 strain.


  1. 1.
    Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present, and future. Antimicrob Agents Chemother 2011; 55(11): 4943–4960CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Zhou T, Zhang X, Guo M, Ye J, Lu Y, Bao Q, Chi W. Phenotypic and molecular characteristics of carbapenem-non-susceptible Enterobacteriaceae from a teaching hospital inWenzhou, southern China. Jpn J Infect Dis 2013; 66(2): 96–102CrossRefPubMedGoogle Scholar
  3. 3.
    Pollett S, Miller S, Hindler J, Uslan D, Carvalho M, Humphries RM. Phenotypic and molecular characteristics of carbapenem-resistant Enterobacteriaceae in a health care system in Los Angeles, California, from 2011 to 2013. J Clin Microbiol 2014; 52(11): 4003–4009CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Schwaber MJ, Lev B, Israeli A, Solter E, Smollan G, Rubinovitch B, Shalit I, Carmeli Y. Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention. Clin Infect Dis 2011; 52(7): 848–855CrossRefPubMedGoogle Scholar
  5. 5.
    El-Herte RI, Kanj SS, Matar GM, Araj GF. The threat of carbapenem-resistant Enterobacteriaceae in Lebanon: an update on the regional and local epidemiology. J Infect Public Health 2012; 5(3): 233–243CrossRefPubMedGoogle Scholar
  6. 6.
    Xu Y, Gu B, Huang M, Liu H, Xu T, Xia W, Wang T. Epidemiology of carbapenem resistant Enterobacteriaceae (CRE) during 2000–2012 in Asia. J Thorac Dis 2015; 7(3): 376–385PubMedPubMedCentralGoogle Scholar
  7. 7.
    Hu FP, Zhu DM, Wang F, Jiang XF, Yang Q, Huang WX, Jia B, Xu YH, Shen JL, Xu YC, Zhang XJ, Hu YJ, Ai XM, Zhang ZX, Ji P, Shan B, Du Y, Zhuo C, Su DH, Wang CQ, Wang AJ, Ni YX, Sun JY, Sun ZY, Chen ZJ, Wei LH, Wu L, Zhang H, Kong Q. CHINET surveillance of distribution and susceptibility of carbapenemresistant Enterobacteriaceae isolates in 2010. Chin J Infect Chemother (Zhongguo Gan Ran Yu Hua Liao Za Zhi) 2013; 13(1): 1–7 (in Chinese)Google Scholar
  8. 8.
    Dai W, Sun S, Yang P, Huang S, Zhang X, Zhang L. Characterization of carbapenemases, extended spectrum β-lactamases and molecular epidemiology of carbapenem-non-susceptible Enterobacter cloacae in a Chinese hospital in Chongqing. Infect Genet Evol 2013; 14: 1–7CrossRefPubMedGoogle Scholar
  9. 9.
    Rasmussen BA, Bush K, Keeney D, Yang Y, Hare R, O’Gara C, Medeiros AA. Characterization of IMI-1 β-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae. Antimicrob Agents Chemother 1996; 40(9): 2080–2086PubMedPubMedCentralGoogle Scholar
  10. 10.
    Clinical and Laboratory Standards Institute. Performance standards for antimiembial susceptibility testing; twenty-fourth informational supplement. CLSI document M100–S25. Wayne, PA: CLSI, 2015Google Scholar
  11. 11.
    Zowawi HM, Sartor AL, Balkhy HH, Walsh TR, Al Johani SM, AlJindan RY, Alfaresi M, Ibrahim E, Al-Jardani A, Al-Abri S, Al Salman J, Dashti AA, Kutbi AH, Schlebusch S, Sidjabat HE, Paterson DL. Molecular characterization of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in the countries of the Gulf cooperation council: dominance of OXA-48 and NDM producers. Antimicrob Agents Chemother 2014; 58(6): 3085–3090CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Queenan AM, Bush K. Carbapenemases: the versatile β-lactamases. Clin Microbiol Rev 2007; 20(3): 440–458CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Dallenne C, Da Costa A, Decre D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. J Antimicrob Chemother 2010; 65(3): 490–495CrossRefPubMedGoogle Scholar
  14. 14.
    Perez-Perez FJ, Hanson ND. Detection of plasmid-mediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol 2002; 40(6): 2153–2162CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nordmann P, Poirel L, Carrer A, Toleman MA, Walsh TR. How to detect NDM-1 producers. J Clin Microbiol 2011; 49(2): 718–721CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol Med 2012; 18(5): 263–272CrossRefPubMedGoogle Scholar
  17. 17.
    Castanheira M, Sader HS, Deshpande LM, Fritsche TR, Jones RN. Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials tested against serine carbapenemase- and metallo-β- lactamase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program. Antimicrob Agents Chemother 2008; 52(2): 570–573CrossRefPubMedGoogle Scholar
  18. 18.
    Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant Gram-negative organisms: extended-spectrum β- lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc 2011; 86(3): 250–259CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Stokes HW, Gillings MR. Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens. FEMS Microbiol Rev 2011; 35(5): 790–819CrossRefPubMedGoogle Scholar
  20. 20.
    Partridge SR. Analysis of antibiotic resistance regions in Gramnegative bacteria. FEMS Microbiol Rev 2011; 35(5): 820–855CrossRefPubMedGoogle Scholar
  21. 21.
    Liu H, Wang Y, Wang G, Xing Q, Shao L, Dong X, Sai L, Liu Y, Ma L. The prevalence of Escherichia coli strains with extended spectrum beta-lactamases isolated in China. Front Microbiol 2015; 6: 335PubMedPubMedCentralGoogle Scholar
  22. 22.
    An S, Chen J, Wang Z, Wang X, Yan X, Li J, Chen Y, Wang Q, Xu X, Li J, Yang J, Wang H, Gao Z. Predominant characteristics of CTX-M-producing Klebsiella pneumoniae isolates from patients with lower respiratory tract infection in multiple medical centers in China. FEMS Microbiol Lett 2012; 332(2): 137–145CrossRefPubMedGoogle Scholar
  23. 23.
    Abdallah HM, Wintermans BB, Reuland EA, Koek A, al Naiemi N, Ammar AM, Mohamed AA, Vandenbroucke-Grauls CM. Extendedspectrum β-lactamase- and carbapenemase-producing enterobacteriaceae isolated from Egyptian patients with suspected blood stream infection. PLoS One 2015; 10(5): e0128120CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Memariani M, Najar Peerayeh S, Zahraei Salehi T, Shokouhi Mostafavi SK. Occurrence of SHV, TEM and CTX-M β-lactamase genes among enteropathogenic Escherichia coli strains isolated from children with diarrhea. Jundishapur J Microbiol 2015; 8(4): e15620CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Giske CG, Fröding I, Hasan CM, Turlej-Rogacka A, Toleman M, Livermore D, Woodford N, Walsh TR. Diverse sequence types of Klebsiella pneumoniae contribute to the dissemination of blaNDM-1 in India, Sweden, and the United Kingdom. Antimicrob Agents Chemother 2012; 56(5): 2735–2738CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Pereira PS, de Araujo CFM, Seki LM, Zahner V, Carvalho-Assef APDA, Asensi MD. Update of the molecular epidemiology of KPC-2-producing Klebsiella pneumoniae in Brazil: spread of clonal complex 11 (ST11, ST437 and ST340). J Antimicrob Chemother 2013; 68(2): 312–316CrossRefPubMedGoogle Scholar
  27. 27.
    Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol 2014; 22(12): 686–696CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kim SY, Shin J, Shin SY, Ko KS. Characteristics of carbapenemresistant Enterobacteriaceae isolates from Korea. Diagn Microbiol Infect Dis 2013; 76(4): 486–490CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  1. 1.Department of Clinical Laboratory ScienceThe 117th Hospital of PLAHangzhouChina

Personalised recommendations