Characterization of Carbapenemases, Extended spectrum beta-lactamases, AmpC, Quinolone resistance and Aminoglycoside resistance determinants in Carbapenem -resistant Enterobacteriaceae clinical isolates in Mainland, China

Volume 6, Issue 3, June 2021     |     PP. 213-241      |     PDF (1229 K)    |     Pub. Date: June 8, 2021
DOI: 10.54647/cm32509    91 Downloads     3389 Views  


Huijuan Chen, College of Life Sciences & Bio-Engineering, Beijing University of Technology, Beijing 100124, China; Institute of Radiation Medicine, Beijing 100850, China.
Qiqi Liu, Institute of Radiation Medicine, Beijing 100850, China.
Gang Wu, College of Animal Science and Technology, Guangxi University, Nanning 530005, China
Shengqi Wang, College of Life Sciences & Bio-Engineering, Beijing University of Technology, Beijing 100124, China; Institute of Radiation Medicine, Beijing 100850, China.

Carbapenem-reistant enterobacteriaceae (CRE) have been significant increasing recently and are highly endemic in China. Several studies demonstrated the prevalence of antibiotic resistance determinants (ARD) in CRE clinical isolates, but there was no comprehensive overview based on ARDs among CRE clinical isolates in Mainland, China. The objectives of this study was assess the prevalence and distribution pattern of carbapenemase genes, ESBL genes, AmpC-encoding genes, aminoglycoside resistant genes and PMQR among CRE clinical isolates in Mainland, China. A systematic literature review was performed by searching different electronic databases including: Pubmed, Embase, CNKI, Wanfang and CQVIP. A random effect model was used to perform the meta-analysis based on comprehensive meta-analysis software.43 studies were included in this meta-analysis. The pooled prevalence of Carbapenemase genes, ESBL genes, AmpC-encoding genes, aminoglycoside resistance genes and PMQR genes in CRE clinical isolates of Mainland, China were 73.3% (95% CI=63.4-81.3), 81.8% (95%CI =74.3-87.4), 32.7% (95% CI=18.6-50.9), 60.6% (95% CI=47.4-72.4) and 70.8% (95%CI= 60.9-79), respectively. KPC (26.1%, 95%CI=18.1-36.1) was the most common type in Carbapenemase genes, followed by NDM (18.4%, 95% CI=12.2-26.7). KPC-2 (26.6%, 95% CI=18.3-36.9), NDM-1 (14%, 95% CI=9.4-20.1), IMP-4 (10.6%, 95% CI=6.6-16.6), VIM-1 (6.1%, 95% CI=3.3-11.3) and OXA-1 (9.8%, 95%CI=3.1-27.3) were the predominant type of a wide range of KPC, NDM, IMP, VIM and OXA variant genes. CTX-M-15 (32.2%, 95%CI= 20.1-47.1), SHV-12 (23.2%, 95% CI=16.5-31.5) and TEM-1 (54.5%, 95%CI=40-68.2) were the main type of CTX-M, SHV and TEM-1 variant genes. CMY-42 (17.1%, 95% CI=5.0-44.7), aac(6’)-Ib (49.0%, 95% CI=36.4-61.6) and aac(6’)-Ib-cr (37.5%, 95% CI=25.5-51.4) was the most frequently type of AmpC-encoding, aminoglycoside resistance and PMQR genes, respectively. KPC-2, TEM-1, CMY-42, aac(6’)-Ib and aac(6’)-Ib-cr were the most common type of Carbapenemase genes, ESBL genes, AmpC-encoding genes, aminoglycoside resistance genes and PMQR genes.

Carbapenemases, ESBL, AmpC, Aminoglycosides, Fluoroquinolones, Carbapenem-resistant enterobacteriaceae

Cite this paper
Huijuan Chen, Qiqi Liu, Gang Wu, Shengqi Wang, Characterization of Carbapenemases, Extended spectrum beta-lactamases, AmpC, Quinolone resistance and Aminoglycoside resistance determinants in Carbapenem -resistant Enterobacteriaceae clinical isolates in Mainland, China , SCIREA Journal of Clinical Medicine. Volume 6, Issue 3, June 2021 | PP. 213-241. 10.54647/cm32509


[ 1 ] Willyard, C. The drug-resistant bacteria that pose the greatest health threats. Nature 2017, 543(7643), 15.
[ 2 ] van Duin, D.; Doi, Y. The global epidemiology of carbapenemase-producing Enterobacter iaceae. Virulence 2017, 8(4), 460-469.
[ 3 ] Zhang, Y.; Wang, Q.; Yin, Y.; Chen, H.; Jin, L.; Gu, B.; Xie, L.; Yang, C.; Ma, X.; Li, H.; Li, W.; Zhang, X.; Liao, K.; Man, S.; Wang, S.; Wen, H.; Li, B.; Guo, Z.; Tian, J.; Pei, F.; Liu, L.; Zhang, L.; Zou, C.; Hu, T.; Cai, J.; Yang, H.; Huang, J.; Jia, X.; Huang, W.; Cao, B.; Wang, H. Epidemiology of Carbapenem-Resistant Enterobac teriaceae Infections: Report from the China CRE Network. Antimicrob Agents Chemother. 2018, 62(2)piie, 01882-17.
[ 4 ] Zhang, R.; Liu, L.; Zhou, H.; Chan, E.W.; Li, J.; Fang, Y.; Li, Y.; Liao, K.; Chen, S. Nationwide Surveillance of Clinical Carbapenem-resistant Enterobacteriaceae (CRE) Strains in China. EBioMedicine. 2017, 19, 98-106.
[ 5 ] Xiao, Y.H.; Wang, J.; Li, Y.; MOH National Antimicrobial Resistance Investigation Net. Bacterial resistance surveillance in China: a report from Mohnarin 2004-2005. Eur J Clin Microbiol Infect Dis 2008, 27(8), 697-708.
[ 6 ] Hu, F.P.; Guo, Y.; Zhu, D.M.; Wang, F.; Jiang, X.F.; Xu, Y.C.; Zhang, X.J.; Zhang, C.X.; Ji, P.; Xie, Y.; Kang, M.; Wang, C.Q.; Wang, A.M.; Xu, Y.H.; Shen, J.L.; Sun, Z.Y.; Chen, Z.J.; Ni, Y.X.; Sun, J.Y.; Chu, Y.Z.; Tian, S.F.; Hu, Z.D.; Li, J.; Yu, Y.S.; Lin, J.; Shan, B.; Du, Y.; Han, Y.; Guo, S.; Wei, L.H.; Wu, L.; Zhang, H.; Kong, J.; Hu, Y.J.; Ai, X.M.; Zhuo, C.; Su, D.H.; Yang, Q.; Jia, B.; Huang, W. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. Clin Microbiol Infect. 2016, 22 Suppl 1,S9-14.
[ 7 ] Logan, L.K.; Renschler, J.P.; Gandra, S.; Weinstein, R.A.; Laxminarayan, R.; Centers for Disease Control Prevention Epicenters Program. Carbapenem-resistant Enterobacteriaceae in children, United States, 1999–2012. Emerg Infect Dis 2015, 21, 2014–21.
[ 8 ] Montagnani, C.; Prato, M.; Scolfaro, C.; Colombo, S.; Esposito, S.; Tagliabue, C.; LoVecchio, A.; Bruzzese, E.; Loy, A.; Cursi, L.; Vuerich, M.; deMartino, M.; Galli, L.; Italian Society of Pediatric Infectious Diseases. Carbapenem-resistant Enterobacteriaceae infections in children: an Italian Retrospective Multicenter Study. Pediatr Infect Dis J 2016, 35, 862–8.
[ 9 ] Nabarro, LEB.; Shankar, C.; Pragasam, A.K.; Mathew, G.; Jeyaseelan, V.; Veeraraghavan, B.; Verghese, V.P. Clinical and bacterial risk factors for mortality in children with carbapenem-resistant Enterobacteriaceae bloodstream infections in India. Pediatr Infect Dis J 2017, 36, e161–6.
[ 10 ] Patel, G.; Huprikar, S.; Factor, S.H.; Jenkins, S.G.; Calfee, D.P. Outcomes of carbapenem-resistant Klebsiella pneumonia infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008, 29(12), 1099–1106.
[ 11 ] Ivanov, I.; Sabtcheva, S.; Dobreva, E.; Todorova, B. Prevalence of carbapenemase genes among 16S Enterobacteriaceae isolate from cancer patients. Probl. Infect. Parasit. Dis 2014, 42(1), 10-13.
[ 12 ] Zasowski, E.J.; Rybak, J.M.; Rybak, M.J. The β-Lactams Strike Back: Ceftazidime-Avib actam. Pharmacotherapy 2015, 35(8), 755-70.
[ 13 ] Livermore, D.M.; Mushtaq, S.; Warner, M.; Zhang, J.C.; Maharjan, S.; Doumith, M.; Woodford, N. Activity of aminoglycosides,including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother. 2011, 66(1), 48-53.
[ 14 ] Zhanel, G.G.; Lawrence, C.K.; Adam, H.; Schweizer, F.; Zelenitsky, S.; Zhanel, M.; Lagacé-Wiens, PRS.; Walkty, A.; Denisuik, A.; Golden, A.; Gin, A.S.; Hoban, D.J.; Lynch, J.P3rd.; Karlowsky, J.A. Imipenem-relebactam and MeropenemVaborbac-tam: Two Novel Carbapenem-β -Lactamase Inhibitor Combinations. Drugs 2018, 78(1), 65-98.
[ 15 ] Petty, L.A.; Henig, O.; Patel, T.S.; Pogue, J.M.; Kaye, K.S. Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae. Infect Drug Resist. 2018, 11, 1461-1472.
[ 16 ] Li, Y.; Shen, H.; Zhu, C.; Yu, Y. Carbapenem-resistant Klebsiella pneumonia infections among ICU admission patients in central China: prevalence and prediction model. Biomed Res Int. 2019, 9767313.
[ 17 ] Higgins, J.P.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ 2003, 327, 557-60.
[ 18 ] Higgins, J.P.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002, 21(11), 1539-58.
[ 19 ] Melsen, W.G.; Bootsma, M.C.; Rovers, M.M.; Bonten, M.J. The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses. Clin Microbiol Infect. 2014, 20(2), 123-9.
[ 20 ] Zhao, D.; Zuo, Y.; Wang, Z.; Li, J. Characterize carbapenem-resistant Klebsiella pneumoniae isolates for nosocomial pneumonia and their Gram-negative bacteria neighbors in the respiratory tract. Mol Biol Rep 2019, 46(1),609-616.
[ 21 ] Fang, L.; Lu, X.; Xu, H. Epidemiology and risk factors for carbapenem-resistant Enterobacteriaceae colonisation and infections: case-controlled study from an academic medical center in a southern area of China. Pathog Dis 2019, 77(4) pii, 5529390.
[ 22 ] Cai, Y.; Chen, C.; Zhao, M.; Yu, X.; Lan, K.; Liao, K.; Guo, P.; Zhang, W.; Ma, X.; He, Y.; Zeng, J.; Chen, L.; Jia, W.; Tang, Y.W.; Huang, B. High Prevalence of Metallo-β-Lactamase -Producing Enterobacter cloacae From Three Tertiary Hospitals in China. Front Microbiol. 2019, 10, 1610.
[ 23 ] Miao, M.; Wen, H.; Xu, P.; Niu, S.; Lv, J.; Xie, X.; Mediavilla, J.R.; Tang, Y.W.; Kreiswirth, B,N.; Zhang, X.; Zhang, H.; Du, H.; Chen, L. Genetic Diversity of Carbapenem-Resistant Enterobacteriaceae (CRE) Clinical Isolates From a Tertiary Hospital in Eastern China. Front Microbiol 2019, 9, 3341.
[ 24 ] Zhou, S.D.; Liu, C.L.; Sun, J.; Jia, L.; Li, Y.; Cao, H.Y.; Yan, H.J.; Sun, J. Resistance genes of carbapenem-resistant enterobacteriaceae in a hospital. Chin J Infect Control 2019, 18(6), 495-504
[ 25 ] Zhang, B.R.; Bi, R.R.; Kong, Z.Y.; Ma, P.; Gu, B. Drug resistance and genotypes of carbapenemase in carbapenem-resistant Enterobacteriaceae strains in Suqian region,China. Chin J Clin Lab Sci 2018, 9, 667-671.
[ 26 ] Bi, R.; Kong, Z.; Qian, H.; Jiang, F.; Kang, H.; Gu, B.; Ma, P. High Prevalence of blaNDM Variants among Carbapenem- Resistant Escherichia coli in Northern Jiangsu Province, China. Front. Microbiol 2018, 9, 2704.
[ 27 ] Jia, X.; Dai, W.; Ma, W.; Yan, J.; He, J.; Li, S.; Li, C.; Yang, S.; Xu, X.; Sun, S.; Shi, J.; Zhang, L. Carbapenem-Resistant E. cloacae in Southwest China: Molecular Analysis of Resistance and Risk Factors for Infections Caused by NDM-1-Producers. Front Microbiol 2018, 9, 658.
[ 28 ] Gong, X.; Zhang, J.; Su, S.; Fu, Y.; Bao, M.; Wang, Y.; Zhang, X. Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the Eastern region of Heilongjiang Province, China. BMC Infect Dis 2018, 18(1), 417.
[ 29 ] Ye, Y.; Xu, L.; Han, Y.; Chen, Z.; Liu, C.; Ming, L. Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates. Exp Ther Med 2018, 15(1), 1143-1149.
[ 30 ] Tian, X.; Sun, S.; Jia, X.; Zou, H.; Li, S.; Zhang, L. Epidemiology of and risk factors for infection with extended-spectrum β-lactamase-producing carbapenem-resistant Enterobacteriaceae: results of a double case-control study. Infect Drug Resist 2018, 11, 1339-1346.
[ 31 ] Tian, D.; Pan, F.; Wang, C.; Sun, Y.; Zhang, H. Resistance phenotype and clinical molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae among pediatric patients in Shanghai. Infect Drug Resist 2018, 11, 1935-1943.
[ 32 ] Dong, F.; Zhang, Y.; Yao, K.; Lu, J.; Guo, L.; Lyu, S.; Yang, Y.; Wang, Y.; Zheng, H.; Song, W.; Liu, G. Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections in a Chinese Children's Hospital: Predominance of New Delhi Metallo-β-Lactamase-1. Microb Drug Resist 2018, 24(2), 154-160.
[ 33 ] Zhang, X.; Chen, D.; Xu, G.; Huang, W.; Wang, X. Molecular epidemiology and drug resistant mechanism in Carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China. PLoS One 2018, 13(3), e0194000.
[ 34 ] Liu, L.; Feng, Y.; Tang, G.; Lin, J.; Huang, W.; Qiao, F.; Zong, Z. Carbapenem-resistant Isolates of the Klebsiella pneumoniae Complex in Western China: The Common ST11 and the Surprising Hospital-specific Types. Clin Infect Dis 2018, 67(suppl_2), S263-S265.
[ 35 ] Ding, H.; Wu, D.Y.; Jiang, L.L.; Li, A.F.; Li, G.X.; Zhao, Z.G. Characteristics of carbapenem -resistance Enterobacteriaceae infection in our hospital and genotypic analysis of carbapenemase genes. Chinese Journal of General Practice 2017, 15(9), 1549-1552.
[ 36 ] Luo, Y.; Luo, R.; Ding, H.; Ren, X.; Luo, H.; Zhang, Y.; Ye, L.; Cui, S. Characterization of Carbapenem-Resistant Escherichia coli Isolates Through the Whole-Genome Sequencing Analysis. Microb Drug Resist 2018, 24(2), 175-180.
[ 37 ] Liang, W.J.; Liu, H.Y.; Duan, G.C.; Zhao, Y.X.; Chen, S.Y.; Yang, H.Y.; Xi, Y.L. Emergence and mechanism of carbapenem-resistant Escherichia coli in Henan, China, 2014. J Infect Public Health 2018, 11(3), 347-351.
[ 38 ] Yan, J.; Pu, S.; Jia, X.; Xu, X.; Yang, S.; Shi, J.; Sun, S.; Zhang, L. Multidrug Resistance Mechanisms of Carbapenem Resistant Klebsiella pneumoniae Strains Isolated in Chongqing, China. Ann Lab Med 2017, 37(5), 398-407.
[ 39 ] Rui, Z.; Dehua, L.; Hua, N.; Yue, F.; Yunmin, X.; L, J.H. Carbapenemase-producing Enterobacteriaceae in Yunnan province, China. Jpn J Infect Dis. 2016, 69(6), 528-530.
[ 40 ] Wang, Q.; Chen, H.; Zhang, Y.; Xian, H.; Liu, Y.; Li, H.; Chen, H.; Wang, X.; Wang, R.; Zhao, C.; Cao, B.; Wang, H. Risk factors and clinical outcomes for carbapenem-resistant Enterobacteriaceae nosocomial infections. Eur J Clin Microbiol Infect Dis 2016, 35(10),1679-89.
[ 41 ] Cheng, L.; Cao, X.L.; Zhang, Z.F.; Ning, M.Z.; Xu, X.J.; Zhou, W.; Chen, J.H.; Zhang, J.H.; Shen, H.; Zhang, K. Clonal dissemination of KPC-2 producing Klebsiella pneumoniae ST11 clone with high prevalence of oqxAB and rmtB in a tertiary hospital in China: results from a 3-year period. Ann Clin Microbiol Antimicrob 2016, 15, 1.
[ 42 ] Huang, W.Z.; Pan, X.N.; Zhang, Q.; Huang, C.Y.; Lao, S.X.; Ning, T. Research on genotypes of carbapenem-resistant enterobacteriaceae in children. Journal of GuangXi Medical University 2016, 33(2), 232-235.
[ 43 ] Yu, J.; Tan, K.; Rong, Z.; Wang, Y.; Chen, Z.; Zhu, X.; Wu, L.; Tan, L.; Xiong, W.; Sun, Z.; Chen, L. Nosocomial outbreak of KPC-2 and NDM-1-producing Klebsiella pneumoniae in a neonatal ward: a retrospective study. BMC Infect Dis 2016, 16(1), 563.
[ 44 ] Cui, L.; Zhao, J.; Lu, J. Molecular characteristics of extended spectrum β-lactamase and carbapenemase genes carried by carbapenem-resistant Enterobacter cloacae in a Chinese university hospital. Turk J Med Sci 2015, 45(6), 1321-8.
[ 45 ] PU, S.L.; Xu, X.Y.; Shi, J.; Zhang, L.P. Characterization of resistance genes and epidemiology of Carbapenem-non susceptible Enterobacter cloacae. J Third Mil Med Univ. 2015, 37(14), 1442-1448.
[ 46 ] Jin, Y.; Shao, C.; Li, J.; Fan, H.; Bai, Y.; Wang, Y. Outbreak of multidrug resistant NDM-1-producing Klebsiella pneumoniae from a neonatal unit in Shandong Province, China. PLoS One 2015, 10(3), e0119571.
[ 47 ] Li, B.; Xu, X.H.; Zhao, Z.C.; Wang, M.H.; Cao, Y.P. High prevalence of metallo-β-lactamase among carbapenem-resistant Klebsiella pneumoniae in a teaching hospital in China. Can J Microbiol.2014, 60(10), 691-5.
[ 48 ] Jian, Z.; Li, Y.; Liu, W.; Li, H.; Zhang, Y.; Li, Y.; Gu, X.; Peng, W. Detection of the novel IMP-38 among carbapenemase-producing Enterobacteriaceae in a university hospital, China.J Infect Dev Ctries. 2014, 8(8), 1044-8.
[ 49 ] Hu, L.; Zhong, Q.; Shang, Y.; Wang, H.; Ning, C.; Li, Y.; Hang, Y.; Xiong, J.; Wang, X.; Xu, Y.; Qin, Z.; Parsons, C.; Wang, L.; Yu, F. The prevalence of carbapenemase genes and plasmid-mediated quinolone resistance determinants in carbapenem-resistant Enterobacteriaceae from five teaching hospitals in central China. Epidemiol Infect 2014, 142(9), 1972-7.
[ 50 ] Zhang, C.M.; Xu, X.Y.; Pu, S.L.; Huang, S.; Sun, J.; Yang, S.; Zhang, L. Characterization of carbapenemases, extended spectrum beta-lactamases, quinolone resistance and aminoglycoside resistance determinants in carbapenem-non-susceptible Escherichia coli from a teaching hospital in Chongqing, Southwest China. Infect Genet Evol 2014, 27, 271-276.
[ 51 ] Liu, Y.; Wan, L.G.; Deng, Q.; Cao, X.W.; Yu, Y.; Xu, Q.F. First description of NDM-1-, KPC-2-, VIM-2- and IMP-4- producing Klebsiella pneumoniae strains in a single Chinese teaching hospital. Epidemiol Infect 2015, 143(2), 376-84.
[ 52 ] 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 in Wenzhou, southern China. Jpn J Infect Dis 2013, 66(2), 96-102.
[ 53 ] Dong, F.; Song, W.Q.; Xu, X.W.; Xu, H.; Liu, X.Q.; Chang, M. Analysis of carbapenemase genotypes in carbapenem-non susceptible Enterobacteriaceae strains isolated from pediatric patients. Chin J Infect Chemother 2013, 13(4), 270-273.
[ 54 ] Li, H.; Zhang, J.; Liu, Y.; Zheng, R.; Chen, H.; Wang, X.; Wang, Z.; Cao, B.; Wang, H. Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: predominance of KPC-2 enzyme. Diagn Microbiol Infect Dis 2014, 78(1), 63-5.
[ 55 ] 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, 1-7.
[ 56 ] Hu, F.; Chen, S.; Xu, X.; Guo, Y.; Liu, Y.; Zhu, D.; Zhang, Y. Emergence of carbapenem-resistant clinical Enterobacteriaceae isolates from a teaching hospital in Shanghai, China. J Med Microbiol 2012, 61(Pt 1), 132-6.
[ 57 ] Hu, Y.Y.; Cai, J.C.; Zhang, R.; Zhou, H.W.; Sun, Q.; Chen, G.X. Emergence of Proteus mirabilis harboring blaKPC-2 and qnrD in a Chinese Hospital. Antimicrob Agents Chemother 2012, 56(5), 2278-82.
[ 58 ] Huang, S.; Dai, W.; Sun, S.; Zhang, X.; Zhang, L. Prevalence of plasmid-mediated quinolone resistance and aminoglycoside resistance determinants among carbapeneme non-susceptible Enterobacter cloacae. PLoS One 2012, 7(10), e47636.
[ 59 ] Liu, Y.; Li, X.Y.; Wan, L.G.; Jiang, W.Y.; Li, F.Q.; Yang, J.H. Molecular characterization of the bla (KPC-2) gene in clinical isolates of carbapenem-resistant Klebsiella pneumoniae from the pediatric wards of a Chinese hospital. Can J Microbiol 2012, 58(10), 1167-73.
[ 60 ] Yang, Q.; Wang, H.; Sun, H.; Chen, H.; Xu, Y.; Chen, M. Phenotypic and genotypic characterization of Enterobacteriaceae with decreased susceptibility to carbapenems: results from large hospital-based surveillance studies in China. Antimicrob Agents Chemother 2010, 54(1), 573-7.
[ 61 ] Li, H.; Zhang, J.; Liu, Y.; Zheng, R.; Chen, H.; Wang, X.; Wang, Z.; Cao, B.; Wang, H. Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: predominance of KPC-2 enzyme. Diagn Microbiol Infect Dis 2014, 78(1), 63-5.
[ 62 ] SU, S.S.; Zhang, J.S.; Wang, Y.; Wang, Y.; Wang, Y.C,; Li, H.L.; Zhang, X.L. Mechanism of quinolone resistance of carbapenem-resistant enterobacteriaceae. Chin J Infect Control 2019 18(2), 99-104.
[ 63 ] Satlin, M.J.; Chen, L.; Patel, G.; Gomez-Simmonds, A.; Weston, G.; Kim, A.C.; Seo, S.K.; Rosenthal, M.E.; Sperber, S.J.; Jenkins, S.G.; Hamula, C.L.; Uhlemann, A.C.; Levi, M.H.; Fries, B.C.; Tang, Y.W.; Juretschko, S.; Rojtman, A.D.; Hong, T.; Mathema, B.; Jacobs, M.R.; Walsh, T.J.; Bonomo, R.A.; Kreiswirth, B.N. Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States. Antimicrob Agents Chemother.2017, 61(4) pii, e02349-16.
[ 64 ] Patel, G.; Bonomo, R.A. "Stormy waters ahead": global emergence of carbapenemases. Front Microbiol.2013, 4, 48.
[ 65 ] Nordmann, P.; Naas, T.; Poirel, L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis.2011, 17(10), 1791-8.
[ 66 ] Ito, H.; Arakawa, Y.; Ohsuka, S.; Wacharotayankun, R.; Kato, N.; Ohta, M. Plasmid-mediated dissemination of the metallo-beta –lactamase gene blaIMP among clinically isolated strains of Serratia marcescens. Antimicrob Agents Chemother.1995, 39(4), 824-9.
[ 67 ] Wang, J.T.; Wu, U.I.; Lauderdale, T.L.; Chen, M.C.; Li, S.Y.; Hsu, L.Y.; Chang, S.C. Carbapenem -nonsusceptible Enterobacteriaceae in Taiwan. PLoS One.2015, 10(3), e0121668.
[ 68 ] Walsh, T.R.; Toleman, M.A.; Poirel, L.; Nordmann, P. Metallo-beta-lactamases: the quiet before the storm? Clin Microbiol Rev 2005, 18(2), 306-25.
[ 69 ] Stewart, A.; Harris, P.; Henderson, A.; Paterson, D. Treatment of infections by OXA-48- Producing Enterobacteriaceae. Antimicrob Agents Chemother 2018, 62(11) pii, e01195-18.
[ 70 ] Wang, Q.; Wang, X.; Wang, J.; Ouyang, P.; Jin, C.; Wang, R.; Zhang, Y.; Jin, L.; Chen, H.; Wang, Z.; Zhang, F.; Cao, B.; Xie, L.; Liao, K.; Gu, B.; Yang, C.; Liu, Z.; Ma, X.; Zhang, X.; Man, S,; Li, W.; Pei, F.; Xu, X.; Jin, Y.; Ji, P.; Wang, H. Phenotypic and Genotypic Characterization of Carbapenem-resistant enterobacteriaceae: Data from a Longitudinal Large-scale CRE Study in China (2012-2016). Clin Infect Dis 2018, 67(suppl_2), S196-S205.
[ 71 ] Sheng, W.H.; Badal, R.E.; Hsueh, P.R.; SMART Program. Distribution of extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases among Enterobacteriaceae isolates causing intra-abdominal infections in the Asia-Pacific region: results of the study for monitoring antimicrobial resistance trends (SMART). Antimicrob Agents Chemother 2013, 57(7), 2981-8.
[ 72 ] Jean, S.S.; Hsueh, P.R.; SMART Asia-Pacific Group. Distribution of ESBL, AmpC β-lactamases and carbapenemases among Enterobacteriaceae isolates causing intra-abdominal and urinary tract infections in the Asia-Pacific region during 2008-14: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother. 2017, 72(1), 166-171.
[ 73 ] Wilson, H.; Török, M.E. Extended-spectrum β-lactamase-producing and carbapenemase- producing Enterobacteriaceae. Microb Genom. 2018, 4(7).
[ 74 ] Philippon, A.; Arlet, G.; Jacoby, G.A. Plasmid-determined AmpC-type ß-lactamases. Antimicrob. Agents Chemother 2002, 46, 1–11.
[ 75 ] Ramirez, M.S.; Tolmasky, M.E. Aminoglycoside modifying enzymes. Drug Resist. Updat 2010, 13, 151–171.
[ 76 ] Fernández-Martínez, M.; RuizDelCastillo, B.; Lecea-Cuello, M.J.; Rodríguez-Baño, J.; Pascual, Á.; Martínez-Martínez, L.; Spanish Network for the Research in Infectious Diseases (REIPI) and the Spanish Group for Nosocomial Infections (GEIH). Prevalence of Aminoglycoside -Modifying Enzymes in Escherichia coli and Klebsiella pneumoniae Producing Extended Spectrum β-Lactamases Collected in Two Multicenter Studies in Spain. Microb Drug Resist. 2018, 24(4), 367-376.
[ 77 ] Taylor, E.; Sriskandan, S.; Woodford, N.; Hopkins, K.L. High prevalence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacteriaceae in the UK and Ireland. Int J Antimicrob Agents 2018, 52(2), 278-282.
[ 78 ] Jacoby, G.A.; Strahilevitz, J.; Hooper, D.C. Plasmid-mediated quinolone resistance. Microbiol Spectr. 2014, 2(5).
[ 79 ] Guillard, T.; Cholley, P.; Limelette, A.; Hocquet, D.; Matton, L.; Guyeux, C.; Lebreil, A.L.; Bajolet, O.; Brasme, L.; Madoux, J.; Vernet-Garnier, V.; Barbe, C.; Bertrand, X.; de Champs On Behalf Of CarbaFrEst Group C. Fluoroquinolone Resistance Mechanisms and population structure of Enterobactercloacae non-susceptible to Ertapenem in North-Eastern France. Front Microbiol. 2015, 6, 1186.
[ 80 ] Machuca, J.; Agüero, J.; Miró, E.; Conejo, MDC.; Oteo, J.; Bou, G.; González-López, J.J.; Oliver, A.; Navarro, F.; Pascual, Á.; Martínez-Martínez, L. Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC β-lactamases and/or carbapenemases in Spain. Enferm Infecc Microbiol Clin. 2017, 35(8), 487-492.
[ 81 ] Yanat, B.; Rodríguez-Martínez, J.M.; Touati, A. Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries. Eur J Clin Microbiol Infect Dis 2016, 36(3), 421-435.
[ 82 ] Chen, X.; Zhang, W.; Pan, W.; Yin, J.; Pan, Z.; Gao, S.; Jiao, X. 2012.Prevalence of qnr, aac(6')-Ib-cr, qepA, and oqxAB in Escherichia coli isolates from humans, animals, and the environment. Antimicrob Agents Chemother 2012, 56(6), 3423-7.