Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Prevalence of Carbapenem-Resistant Enterobacterales and Their Diverse Resistance Mechanisms

  • Sohyeong Kim (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan) ;
  • Sang Rae Kim (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan) ;
  • Xianglan Xuan (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan) ;
  • Yujin Park (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan) ;
  • Seung Jun Roh (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan) ;
  • Sunghyun Kim (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
  • Received : 2024.05.31
  • Accepted : 2024.06.24
  • Published : 2024.09.30
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Abstract

This review provides an overview of carbapenem-resistant Enterobacterales (CRE) studies. CRE, called superbugs, has a high mortality rate and an increased resistance rate in several countries. The bacteria representing CRE are Klebsiella species and Escherichia spp., and they cause urinary tract infections (UTIs) and bloodstream infections (BSIs). CRE acquires resistance due to several mechanisms, typically divided into carbapenemase-producing (CP)-CRE and non-CP-CRE. Furthermore, although there are several antibiotics developed to treat CRE, they have their limitations; thus, antibiotic combination therapies or novel treatments are being developed. Therefore, since research on CRE and the use of appropriate antibiotics is important, some CRE-resistant mechanisms that enhance them are discussed. This review article was written using information obtained from Google Scholar and the National Center for Biotechnology Information website.

Keywords

Acknowledgement

This paper was supported by a research fund from the Catholic University of Pusan and by the BB21plus fund by Busan Metropolitan City and Busan Techno Park.

References

  1. Baek YH, Shin KS. Carbapenemase-producing enterobacterales: Epidemiology, detection, and treatment. Biomedical Science Letters. 2023. 29: 109-120.
  2. Blais J, Lopez S, Li C, Ruzin A, Ranjitkar S, Dean CR, Leeds JA, Casarez A, Simmons RL, Reck F. In vitro activity of lys228, a novel monobactam antibiotic, against multidrug-resistant enterobacteriaceae. Antimicrobial Agents and Chemotherapy. 2018. 62: 10.1128/aac. 00552-00518.
  3. Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, Westblade LF. Carbapenemase-producing organisms: A global scourge. Clinical Infectious Diseases. 2018. 66: 1290-1297.
  4. Codjoe FS, Donkor ES. Carbapenem resistance: A review. Medical Sciences. 2017. 6: 1.
  5. Colclough AL, Alav I, Whittle EE, Pugh HL, Darby EM, Legood SW, McNeil HE, Blair JM. Rnd efflux pumps in gram-negative bacteria; regulation, structure and role in antibiotic resistance. Future Microbiology. 2020. 15: 143-157.
  6. Courvalin P. Transfer of antibiotic resistance genes between gram-positive and gram-negative bacteria. Antimicrobial Agents and Chemotherapy. 1994. 38: 1447-1451.
  7. Dang B, Mao D, Luo Y. Complete nucleotide sequence of incp-1β plasmid pdtc28 reveals a non-functional variant of the bla ges-type gene. PLoS One. 2016. 11: e0154975.
  8. Fernandez L, Hancock RE. Adaptive and mutational resistance: Role of porins and efflux pumps in drug resistance. Clinical Microbiology Reviews. 2012. 25: 661-681.
  9. Garg A, Garg J, Kumar S, Bhattacharya A, Agarwal S, Upadhyay G. Molecular epidemiology & therapeutic options of carbapenem-resistant gram-negative bacteria. Indian Journal of Medical Research. 2019. 149: 285-289.
  10. Garza-Gonzalez E, Bocanegra-Ibarias P, Bobadilla-del-Valle M, Ponce-de-Leon-Garduno LA, Esteban-Kenel V, Silva-Sanchez J, Garza-Ramos U, Barrios-Camacho H, Lopez-Jacome LE, Colin-Castro CA. Drug resistance phenotypes and genotypes in mexico in representative gram-negative species: Results from the infivar network. PLoS One. 2021. 16: e0248614.
  11. Goodman K, Simner P, Tamma P, Milstone A. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant enterobacteriaceae (cre). Expert Review of Anti-Infective Therapy. 2016. 14: 95-108.
  12. Jamal AJ, Mataseje LF, Williams V, Leis JA, Tijet N, Zittermann S, Melano RG, Mulvey MR, Katz K, Allen VG. Genomic epidemiology of carbapenemase-producing enterobacterales at a hospital system in toronto, ontario, canada, 2007 to 2018. Antimicrobial Agents and Chemotherapy. 2021. 65: 10.1128/aac. 00360-00321.
  13. Ji S, Lv F, Du X, Wei Z, Fu Y, Mu X, Jiang Y, Yu Y. Cefepime combined with amoxicillin/clavulanic acid: A new choice for the kpc-producing K. pneumoniae infection. International Journal of Infectious Diseases. 2015. 38: 108-114.
  14. Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The "old" and the "new" antibiotics for mdr gram-negative pathogens: For whom, when, and how. Front Public Health. 2019. 7: 151.
  15. Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: An overview. Cold Spring Harbor Perspectives in Medicine. 2016. 6: a027029.
  16. Lee C-M, Lai C-C, Chiang H-T, Lu M-C, Wang L-F, Tsai T-L, Kang M-Y, Jan Y-N, Lo Y-T, Ko W-C. Presence of multidrug-resistant organisms in the residents and environments of long-term care facilities in taiwan. Journal of Microbiology, Immunology and Infection. 2017. 50: 133-144.
  17. Lin DM, Koskella B, Lin HC. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World Journal of Gastrointestinal Pharmacology and Therapeutics. 2017. 8: 162.
  18. Liu B, Trout REL, Chu G-H, McGarry D, Jackson RW, Hamrick JC, Daigle DM, Cusick SM, Pozzi C, De Luca F, Benvenuti M, Mangani S, Docquier J-D, Weiss WJ, Pevear DC, Xerri L, Burns CJ. Discovery of taniborbactam (vnrx-5133): A broad-spectrum serine- and metallo-β-lactamase inhibitor for carbapenem-resistant bacterial infections. Journal of Medicinal Chemistry. 2020. 63: 2789-2801.
  19. Lomovskaya O, Sun D, Rubio-Aparicio D, Nelson K, Tsivkovski R, Griffith DC, Dudley MN. Vaborbactam: Spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in enterobacteriaceae. Antimicrobial Agents and Chemotherapy. 2017. 61: 10.1128/aac. 01443-01417.
  20. Lutgring JD. Carbapenem-resistant enterobacteriaceae: An emerging bacterial threat. Seminars in Diagnostic Pathology. 2019. 36: 182-186.
  21. Lutgring JD, Limbago BM. The problem of carbapenemaseproducing-carbapenem-resistant-enterobacteriaceae detection. Journal of Clinical Microbiology. 2016. 54: 529-534.
  22. Ma J, Song X, Li M, Yu Z, Cheng W, Yu Z, Zhang W, Zhang Y, Shen A, Sun H. Global spread of carbapenem-resistant enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy. Microbiological Research. 2023. 266: 127249.
  23. Mmatli M, Mbelle NM, Maningi NE, Osei Sekyere J. Emerging transcriptional and genomic mechanisms mediating carbapenem and polymyxin resistance in enterobacteriaceae: A systematic review of current reports. Msystems. 2020. 5: 10.1128/msystems.00783-00720.
  24. Muscarella LF. Risk of transmission of carbapenem-resistant enterobacteriaceae and related "superbugs" during gastrointestinal endoscopy. World Journal of Gastrointestinal Endoscopy. 2014. 6: 457.
  25. Nicolau DP. Carbapenems: A potent class of antibiotics. Expert Opinion on Pharmacotherapy. 2008. 9: 23-37.
  26. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: Past, present, and future. Antimicrobial Agents and Chemotherapy. 2011. 55: 4943-4960.
  27. Perovic O, Ismail H, Quan V, Bamford C, Nana T, Chibabhai V, Bhola P, Ramjathan P, Swe Swe-Han K, Wadula J. Carbapenem-resistant enterobacteriaceae in patients with bacteraemia at tertiary hospitals in south africa, 2015 to 2018. European Journal of Clinical Microbiology & Infectious Diseases. 2020. 39: 1287-1294.
  28. Porreca AM, Sullivan KV, Gallagher JC. The epidemiology, evolution, and treatment of kpc-producing organisms. Current Infectious Disease Reports. 2018. 20: 1-12.
  29. Potter RF, D'Souza AW, Dantas G. The rapid spread of carbapenem-resistant enterobacteriaceae. Drug Resistance Updates. 2016. 29: 30-46.
  30. Queenan AM, Bush K. Carbapenemases: The versatile β-lactamases. Clinical Microbiology Reviews. 2007. 20: 440-458.
  31. Queenan AM, Shang W, Flamm R, Bush K. Hydrolysis and inhibition profiles of β-lactamases from molecular classes a to d with doripenem, imipenem, and meropenem. Antimicrobial Agents and Chemotherapy. 2010. 54: 565-569.
  32. Rahman MS, Koh Y-S. A novel antibiotic agent, cefiderocol, for multidrug-resistant gram-negative bacteria. Journal of Bacteriology and Virology. 2020. 50: 218-226.
  33. Shankar C, Nabarro LE, Anandan S, Veeraraghavan B. Minocycline and tigecycline: What is their role in the treatment of carbapenem-resistant gram-negative organisms? Microbial Drug Resistance. 2017. 23: 437-446.
  34. Shields RK, Doi Y. Aztreonam combination therapy: An answer to metallo-β-lactamase-producing gram-negative bacteria? Clinical Infectious Diseases. 2019. 71: 1099-1101.
  35. Shin SY, Bae IK, Kim J, Jeong SH, Yong D, Kim JM, Lee K. Resistance to carbapenems in sequence type 11 Klebsiella pneumoniae is related to dha-1 and loss of ompk35 and/or ompk36. Journal of Medical Microbiology. 2012. 61: 239-245.
  36. Shirley M. Ceftazidime-avibactam: A review in the treatment of serious gram-negative bacterial infections. Drugs. 2018. 78: 675-692.
  37. Silver LL. Fosfomycin: Mechanism and resistance. Cold Spring Harbor Perspectives in Medicine. 2017. 7: a025262.
  38. Suay-Garcia B, Perez-Gracia MT. Present and future of carbapenem-resistant enterobacteriaceae (cre) infections. Antibiotics (Basel). 2019. 8.
  39. Tamma PD, Goodman KE, Harris AD, Tekle T, Roberts A, Taiwo A, Simner PJ. Comparing the outcomes of patients with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant enterobacteriaceae bacteremia. Clinical Infectious Diseases. 2017. 64: 257-264.
  40. Tawfick MM, Alshareef WA, Bendary HA, Elmahalawy H, Abdulall AK. The emergence of carbapenemase bla ndm genotype among carbapenem-resistant enterobacteriaceae isolates from egyptian cancer patients. European Journal of Clinical Microbiology & Infectious Diseases. 2020. 39: 1251-1259.
  41. Tilahun M, Kassa Y, Gedefie A, Ashagire M. Emerging carbapenem-resistant enterobacteriaceae infection, its epidemiology and novel treatment options: A review. Infection and Drug Resistance. 2021. 4363-4374.
  42. Tompkins K, van Duin D. Treatment for carbapenem-resistant enterobacterales infections: Recent advances and future directions. European Journal of Clinical Microbiology & Infectious Diseases. 2021. 40: 2053-2068.
  43. Tsai Y-K, Liou C-H, Fung C-P, Lin J-C, Siu LK. Single or in combination antimicrobial resistance mechanisms of Klebsiella pneumoniae contribute to varied susceptibility to different carbapenems. PLoS One. 2013. 8: e79640.
  44. Tsilipounidaki K, Athanasakopoulou Z, Muller E, Burgold-Voigt S, Florou Z, Braun SD, Monecke S, Gatselis NK, Zachou K, Stefos A. Plethora of resistance genes in carbapenem-resistant gram-negative bacteria in greece: No end to a continuous genetic evolution. Microorganisms. 2022. 10: 159.
  45. Van Duin D, Arias CA, Komarow L, Chen L, Hanson BM, Weston G, Cober E, Garner OB, Jacob JT, Satlin MJ. Molecular and clinical epidemiology of carbapenem-resistant enterobacterales in the USA (crackle-2): A prospective cohort study. The Lancet Infectious Diseases. 2020. 20: 731-741.
  46. Walsh T. The emergence and implications of metallo-β-lactamases in gram-negative bacteria. Clinical Microbiology and Infection. 2005. 11: 2-9.
  47. Wang Q, Wang X, Wang J, Ouyang P, Jin C, Wang R, Zhang Y, Jin L, Chen H, Wang Z. Phenotypic and genotypic characterization of carbapenem-resistant enterobacteriaceae: Data from a longitudinal large-scale cre study in china (2012-2016). Clinical Infectious Diseases. 2018. 67: S196-S205.
  48. Weston N, Sharma P, Ricci V, Piddock LJ. Regulation of the acrab-tolc efflux pump in enterobacteriaceae. Research in Microbiology. 2018. 169: 425-431.
  49. Wu JY, Srinivas P, Pogue JM. Cefiderocol: A novel agent for the management of multidrug-resistant gram-negative organisms. Infectious Diseases and Therapy. 2020. 9: 17-40.
  50. Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z. Ndm metallo-β-lactamases and their bacterial producers in health care settings. Clinical Microbiology Reviews. 2019. 32: 10.1128/cmr.00115-00118.
  51. Yang Y, Wu P, Livermore D. Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. Antimicrobial Agents and Chemotherapy. 1990. 34: 755-758.
  52. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, Alberti S, Bush K, Tenover FC. Novel carbapenem-hydrolyzing β-lactamase, kpc-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. 2001. 45: 1151-1161.
  53. Zhang Y, Wang Q, Yin Y, Chen H, Jin L, Gu B, Xie L, Yang C, Ma X, Li H. Epidemiology of carbapenem-resistant enterobacteriaceae infections: Report from the china cre network. Antimicrobial Agents and Chemotherapy. 2018. 62: 10.1128/aac.01882-01817.
  54. Zou X, Jin S, Chen L, Li J, Zhang X, Zhou H, Li X, Huang H. Antibacterial activity of eravacycline against carbapenem-resistant gram-negative isolates in china: An in vitro study. Infection and Drug Resistance. 2023. 2271-2279.