Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Carbapenemase-Producing Enterobacterales: Epidemiology, Detection, and Treatment

  • Yun Hee Baek (Department of Microbiology, Chungbuk National University College of Medicine) ;
  • Kyeong Seob Shin (Department of Laboratory Medicine, Chungbuk National University College of Medicine)
  • Received : 2023.09.11
  • Accepted : 2023.09.21
  • Published : 2023.09.30
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Abstract

Recently, the explosive increase of carbapenemase-producing Enterobacterales (CPE) in the worldwide poses a serious threat. The purpose of this study is to investigate epidemiology, detection, and treatment of CPE. Three main carbapenemase are reported worldwide, which were KPC, NDM, and OXA-48-like. KPC type are mostly found in USA, China, Europe, and Latin America. NDM type are mostly found in South Asia. OXA-48-like are often seen in the Mediterranean and Northern Africa. In Korea, CPE have increased explosively since 2015. In 2021, 18,099 CPE were isolated, which were Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae in order. The CPE genotype was distributed with KPC, NDM, OXA type in order. Phenotypic detection methods include carbapenemase production tests (CPT) and differential tests of CPE. CPTs include modified Hodge test, modified carbapenem inactivation method (mCIM), Carba NP test, among which mCIM is the most widely used due to easy accessibility and accuracy. A lot of genotypic methods are being done for quick results, and commercialized kits using multiplex real-time PCR and microarray are widely used. Colistin and tigecycline are used as the first line of CPE treatment and are used in combination with second line drugs such as meropenem and fosfomycin.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF- 2021R1I1A1A01049073 to Y.H.B.).

References

  1. Barbour A, Schmidt S, Ma B, Schiefelbein L, Rand KH, Burkhardt O, et al. Clinical pharmacokinetics and pharmacodynamics of tigecycline. Clin Pharmacokinet. 2009. 48: 575-584. https://doi.org/10.2165/11317100-000000000-00000
  2. Bergen PJ, Landersdorfer CB, Zhang J, Zhao M, Lee HJ, Nation RL, et al. Pharmacokinetics and pharmacodynamics of 'old' polymyxins: what is new? Diagn Microbiol Infect Dis. 2012. 74: 213-223. https://doi.org/10.1016/j.diagmicrobio.2012.07.010
  3. Castanheira M, Farrell SE, Krause KM, Jones RN, Sader HS. Contemporary diversity of b-lactamase among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent β-lactamase groups. Antimicrob Agents Chemother. 2014. 58: 833-838. https://doi.org/10.1128/AAC.01896-13
  4. Castanheira M, Rhomberg PR, Flamm RK, Jones RN. Effect of the β-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016. 60: 5454-5458. https://doi.org/10.1128/AAC.00711-16
  5. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol. 2014. 22: 686-696. https://doi.org/10.1016/j.tim.2014.09.003
  6. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; M100-S19. Clinical and Laboratory Standards Institute, 2009, Wayne, PA.
  7. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; M100-S28. Clinical and Laboratory Standards Institute, 2018, Wayne, PA.
  8. Dodemont M, De Mendonca R, Nonhoff C, Roisin S, Denis O, et al. Performance of the Verigene Gram-negative blood culture assay for rapid detection of bacteria and resistance determinants. J Clin Microbiol. 2014. 52: 3085.
  9. Doi Y, Paterson DL. Carbapenemae-producing Enterobacteriaceae. Semin Respir Crit Care Med. 2015. 36: 74-84. https://doi.org/10.1055/s-0035-1544208
  10. Dortet L, Poirel L, Nordmann P. Rapid identification of carbapenemase types in Enterobacteriaceae and Pseudomonas spp. By using a biochemical test. Antimicrob Agents Chemother. 2012. 56: 6437-6440. https://doi.org/10.1128/AAC.01395-12
  11. Falagas ME, Marki S, Karageorgopoulos DE, Katoris AC, Mavromanolakis E, Samonis G. Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to Fosfomycin. Int J Antimicrob Agents. 2010. 35: 24-43. https://doi.org/10.1016/j.ijantimicag.2009.10.019
  12. Girlich D, Poirel L, Nordmann P. Value of the modified Hodge test for detection of emerging carbapenemases in Enterobacteriaceae. J Clin Microbiol. 2012. 50: 477-479. https://doi.org/10.1128/JCM.05247-11
  13. Girlich D, Halimi D, Zambardi G, Nordmann P. Evaluation of Etest strips for detection of KPC and metallo-carbapenemase in Enterobacteriaceae. Diagn Microbiol Infect Dis. 2013. 77: 200-201. https://doi.org/10.1016/j.diagmicrobio.2013.08.002
  14. Hong SK, Yong D, Kim K, Hong SS, Hong SG, Khosbayar T, et al. First outbreak of KPC-2-producing Klebsiella pneumoniae sequence type 258 in a hospital in South Korea. J Clin Microbiol. 2013. 51: 3877-3879. https://doi.org/10.1128/JCM.01730-13
  15. Jacoby GA, Munoz-Price LS. The new beta-lactamases. N Engl J Med. 2005. 352: 380.
  16. Jeong SH, Lee KM, Lee J, Bae IK, Kim JS, Kim HS, et al. Clonal and horizontal spread of the blaOXA-232 gene among Enterobacteriaceae in a Korean hospital. Diagn Microbiol Infect Dis. 2015. 82: 70-77. https://doi.org/10.1016/j.diagmicrobio.2015.02.001
  17. Johansson A, Ekelof J, Giske CG, Sundqvist M. The detection and verification of carbapenemases using ertapenem and matrix assisted laser desorption ionization-time of flight. BMC Microbiol. 2014. 14: 89-96. https://doi.org/10.1186/1471-2180-14-89
  18. Kim MN, Yong D, An D, Chung HS, Woo JH, Lee K, et al. Nosocomial clustering of NDM-1 producing Klebsiella pneumoniae sequence type 340 strains in four patients at a South Korean tertiary care hospital. J Clin Microbiol. 2012. 50: 1433-1436. https://doi.org/10.1128/JCM.06855-11
  19. Kimura S, Ishii Y, Yamaguchi K. Evaluation of dipicolinic acid for detection of IMP-or VIM-type metallo-β-lactamase-producing Pseudomonas aeruginosa clinical isolates. Diagn Microbiol Infect Dis. 2005. 53: 241-244. https://doi.org/10.1016/j.diagmicrobio.2005.05.017
  20. Korea Disease Control and Prevention Agency (KDCPA). 2022. National antimicrobial resistance surveillance in Korea, 2021 Annual report. https:/www.kdca.go.kr/nohas.
  21. Landman D, Salvani JK, Bratu S, Quale J. Evaluation of techniques for detection of carbapenem-resistant Klebsiella pneumoniae in stool surveillance cultures. J Clin Microbiol. 2005. 43: 5639-5641. https://doi.org/10.1128/JCM.43.11.5639-5641.2005
  22. Lebreton F, Corey BW, McFlheny CL, Iovleva A, Preston L, Margulieux KR, et al. Charactererization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of Citrobacter koseri. Antimicrob Agents and Chemother. 2021. 65: e0015021.
  23. Lee C, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: Epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016. 7: 1-30. https://doi.org/10.3389/fmicb.2016.00895
  24. Lee K, Lim YS, Yong D, Yum J, Chong Y. Evaluation of the Hodge Test and the imipenem-EDTA double disk synergy test for differentiating metallo-β-lactamase producing isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol. 2003. 41: 4623-4629. https://doi.org/10.1128/JCM.41.10.4623-4629.2003
  25. Lee K, Kim CK, Yong D, Jeong SH, Yum YH, Seo YH, et al. Improved performance of the modified Hodge test with MacConkey agar for screening carbapenemase-producing Gram-negative bacilli. J Microbiol Methods. 2010. 83: 149-152. https://doi.org/10.1016/j.mimet.2010.08.010
  26. Lutgring JD, Limbago BM. The problem of carbapenemas-producing-carbapenem-resistant Enterobacteriaceae detection. J Clin Microbiol. 2016. 54: 529-534. https://doi.org/10.1128/JCM.02771-15
  27. Maltezou HC. Metallo-β-lactamase in Gram negative bacteria: introducing the era of pan-resistance? Int J Antimicrob Agents. 2009. 33: 405. e1-7. https://doi.org/10.1016/j.ijantimicag.2008.09.003
  28. Mammina C, Bonura C, Di Bernardo F, Aleo A, Fascina T, Sodano C, et al. Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011. Euro Surveill. 2012. 17: 20248.
  29. Mathers AJ, Stoesser N, Sheppard AE, Pankhurst L, Giess A, Yeh AJ, et al. Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae at a single institution: insights into endemicity from whole-genome sequencing. Antimicrob Agents Chemother. 2015. 59: 1656-1663. https://doi.org/10.1128/AAC.04292-14
  30. Monteiro J, Widen RH, Pignatari AC, Kubasek C, Siberts S, et al. Rapid detection of carbapenemase genes by multiplex realtime PCR. J Antimicrob Chemother. 2012. 67: 906.
  31. Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemase. Lancet Infect Dis. 2013. 13: 785-796. https://doi.org/10.1016/S1473-3099(13)70190-7
  32. Naas T, Cuzon G, Villegas MV, Lartigue MF, Quinn JP, Nordmann P. Genetic structures at the origin of acquisition of the β-lactamase blaKPC gene. Antimicrob Agents Chemother. 2008. 52: 1257-1263. https://doi.org/10.1128/AAC.01451-07
  33. Naparstek L, Carmeli Y, Navon-Venezia S, Banin E. Biofilm formation and susceptibility to gentamicin and colistin of extremely drug-resistant KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother. 2014. 69. 1027-1034. https://doi.org/10.1093/jac/dkt487
  34. Navarro-San Fransisco FC, Mora-Rillo M, Romero-Gomez MP, Moreno-Ramos F, Rico-Nieto A, Ruiz-Carrascoso G, et al. Bacteremia due to OXA-48-carbapenemase-producing Enterobacteriaceae; a major clinical challenge. Clin Microbiol Infect. 2013. 19: e72-e79. https://doi.org/10.1111/1469-0691.12091
  35. Nordmann P, Poirel L. Emerging carbapenemase in Gram-negative aerobes. Clin Microbiol Infect. 2002. 8: 321-331. https://doi.org/10.1046/j.1469-0691.2002.00401.x
  36. Nordmann P, Poirel P, Dortet L. Rapid detection of carbapenemasproducing Enterobacteriaceae. Emerg Infect Dis. 2012. 18: 1503-1507. https://doi.org/10.3201/eid1809.120355
  37. Nordmann P, Poirel L. The difficult-to control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect. 2014. 20: 821-830. https://doi.org/10.1111/1469-0691.12719
  38. Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin Infect Dis. 2007. 45: 1179.
  39. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother. 2012. 67: 1597.
  40. Potron A, Poirel L, Rondinaud E, Nordmann P. Intercontinental spread of OXA-48 β-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011. Euro Surveill. 2013. 18: 20549.
  41. Qin S, Fu Y, Zhang Q, Qi H, Wen JG, Xu H, et al. High incidence and endemic spread NDM-1 positive Enterobacteriaceae in Henan Province, China. Antimicrob Agents Chemother. 2014. 58: 4275-4282. https://doi.org/10.1128/AAC.02813-13
  42. Queenan AM, Bush K. Carbapenemases: the versatile betalactamases. Clin Microbiol Rev. 2007. 20: 440.
  43. Rhee JY, Park YK, Shin JY, Choi JY, Lee MY, Peck KR, et al. KPC-producing extreme drug-resistant Klebsiella pneumoniae isolate form a patient with diabetes mellitus and chronic renal failure on hemodialysis in South Korea. Antimicrob Agents Chemother. 2010. 54: 2278-2279. https://doi.org/10.1128/AAC.00011-10
  44. Rodriguez-Bano J, Gutierrez-Gutierrez B, Machuca I, Pascual A. Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clin Microbiol Rev. 2018. 31: e00079-17.
  45. Stuart JC, Leverstein-Van Hall MA. Duch Working Party on the Detection of Highly Resistant Microorganisms. Guideline for phenotypic screening and confirmation of carbapenemase in Enterobacteriaceae. Int J Antimicrob Agents. 2010. 36: 205-210. https://doi.org/10.1016/j.ijantimicag.2010.05.014
  46. Tangden T, Hickman RA, Forsberg P, Lagerback P, Giske CG, Cars O. Evaluation of double-and triple-antibiotic combination for VIM- and NDM-producing Klebsiella pneumoniae by in vitro time-kill experiments. Antimicrob Agents Chemother. 2014. 58: 1757-1762. https://doi.org/10.1128/AAC.00741-13
  47. Tzouvelekis LS, Markogiannakis A, Psicholgiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae; an evolving crisis of global dimensions. Clin Microbiol Rev. 2012. 25: 682-707. https://doi.org/10.1128/CMR.05035-11
  48. van der Zwaluw K, de Haan A, Pluister GN, Blltsma HJ, de Neeling AJ, Schouls LM. The carbapenem inactivation method (CIM), a simple and low-cost alternative for the Carba NP test to asses phenotypic carbapenemase activity in gram-negative rods. PLoS One. 2015. 10: e0123690.
  49. Vasso S, Cunningham SA, Kohner PC, Mandrekar JN, Lolans K, Hayden MK, et al. Rapid and direct real-time detection of blaKPC and blaNDM from surveillance samples. J Clin Microbiol. 2013. 51: 3609-36012. https://doi.org/10.1128/JCM.01731-13
  50. Walther-Rasmussen J, Hoiby N. OXA-type carbapenemases. J Antimicrob Chemother. 2006. 57: 373.
  51. Walther-Rasmussen J, Hoiby N. Class A carbapenemases. J Antimicrob Chemother. 2007. 60: 470.
  52. Wang X, Zhang F, Zhao C, Wang Z, Nichols WW, Testa R, et al. In vitro activities of ceftazidime-avibactam and aztreonam-avibactam against 373 gram-negative bacilli collected in 2011 and 2012 from 11 teaching hospitals in China. Antimicrob Agents Chemother. 2014. 58: 1774-1778. https://doi.org/10.1128/AAC.02123-13
  53. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001. 45: 1151.
  54. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-β-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009. 53: 5046.
  55. Yoon EJ, Kim JO, Kim D, Lee H, Yang JW, Lee KJ, et al. Klebsiella pneumoniae carbapenemase producers in South Korea between 2013 and 2015. Front Microbiol. 2018. 9: 1-8. https://doi.org/10.3389/fmicb.2018.00001