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VOLUME 29 , ISSUE 1 ( January, 2025 ) > List of Articles

Original Article

Clinical Predispositions, Features, and Outcomes of Infections with Carbapenem-resistant Enterobacterales among Critical Care Patients

Ahmed R El-Karamany Shoala, Yasser Nassar, Amani A El-Kholy, Noha S Soliman, Alia Abdel-Fattah, Helmy El-Ghawaby

Keywords : Carbapenemase, Carbapenem-resistant Enterobacterales, NDM gene, Outcome, OXA-48 gene, Risk factors

Citation Information : Shoala AR, Nassar Y, El-Kholy AA, Soliman NS, Abdel-Fattah A, El-Ghawaby H. Clinical Predispositions, Features, and Outcomes of Infections with Carbapenem-resistant Enterobacterales among Critical Care Patients. Indian J Crit Care Med 2025; 29 (1):36-44.

DOI: 10.5005/jp-journals-10071-24876

License: CC BY-NC 4.0

Published Online: 30-12-2024

Copyright Statement:  Copyright © 2025; The Author(s).


Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) infections pose a significant global public health threat. We aimed to assess the risk variables, clinical characteristics, and outcomes of CRE-caused infections in criticalcare patients. Patients and methods: This prospective study enrolled 181 adult patients infected with Enterobacterales in the intensive care unit (ICU). Patients underwent clinical assessment and monitoring throughout their ICU stay. Carbapenem resistance was identified through antibiotic susceptibility testing and multiplex molecular detection of carbapenemase-encoding genes. Results: The mean age of patients was 67.99 ± 12.89 years, with 71.3% being males. Of 181 patients, 111 (61.3%) were found to have CRE infections, including 39 Klebsiella pneumoniae and 31 Escherichia coli isolates. The CRE isolates showed the predominance of the OXA-48 (74.8%), followed by the NewDelhi Metallobetalactamase (NDM) carbapenemase genes (20.7%). The risk factors associated with CRE infection included high sequential organ failure assessment (SOFA) score, prolonged length of stay (LOS) in ICU, prior use of broad-spectrum antimicrobials, hemodialysis, plasma exchange, and prolonged mechanical ventilation. Carbapenem-resistant Enterobacterales infections significantly required longer LOS, more need for mechanical ventilation, and exhibited lower rates of bacterial elimination than carbapenem-susceptible Enterobacterales (CSE) infections. The type of resistance gene did not significantly influence the mortality rate among CRE patients. The successful treatment of OXA-48-positive CRE showed a strong correlation with tigecycline and colistin antibiotics. Conclusion: Carbapenem-resistant Enterobacterales infection in ICU patients was associated with adverse outcomes. Identification of high-risk patients is essential for early diagnosis and appropriate management. Therefore, it is crucial to improve infection control methods and implement antimicrobial stewardship to avoid spreading infections.

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  1. Sikora A, Zahra F. Nosocomial Infections. Treasure Island (FL): StatPearls Publishing; 2024. PMID: 32644738.
  2. Diene SM, Rolain JM. Investigation of antibiotic resistance in the genomic era of multidrug-resistant Gram-negative bacilli, especially Enterobacteriaceae, Pseudomonas and Acinetobacter. Expert Rev Anti Infect Ther 2013;11(3):277–296. DOI: 10.1586/eri.13.1. PMID: 23458768.
  3. Abou-assy RS, Aly MM, Amashah RH, Jastaniah SD, Al Deen HM. Epidemiology of carbapenem resistance Enterobacterales in Saudi Arabia: A systematic review. J Contemp Med Sci 2022;8(1):18–26. DOI: 10.22317/jcms.v8i1.1168.
  4. Savard P, Perl TM. Combating the spread of carbapenemases in Enterobacteriaceae: a battle that infection prevention should not lose. Clin Microbiol Infect 2014;20(9):854–861. DOI: 10.1111/1469-0691.12748.
  5. Nordmann P, Cornaglia G. Carbapenemase-producing Enterobacteriaceae: A call for action! Clin Microbiol Infect 2012;18(5):411–412. DOI: 10.1111/j.1469-0691.2012.03795.x.
  6. Dos Santos GS, Solidônio EG, Costa MC, Melo RO, de Souza IF, Silva G, et al. Study of the Enterobacteriaceae Group CESP (Citrobacter, Enterobacter, Serratia, Providencia, Morganella and Hafnia): A review. In: Méndez-Vilas A (Ed). The Battle Against Microbial Pathogens: Basic Science, Technological Advances and Educational Programs. Recife: Fideral University of Pernambuco; 2015. pp. 794–805.
  7. Alotaibi BS, Tantry BA, Farhana A, Alammar MA, Shah NN, Mohammed AH, et al. Resistance pattern in Mostly Gram-negative bacteria causing urinary tract infections. Infect Disord Drug Targets 2023;23(2):e280922209238. DOI: 10.2174/1871526522666220928115043.
  8. Segagni Lusignani L, Presterl E, Zatorska B, Van den Nest M, Diab-Elschahawi M. Infection control and risk factors for acquisition of carbapenemase-producing Enterobacteriaceae. A 5 year (2011–2016) case-control study. Antimicrob Resist Infect Control 2020;9(1):18. DOI: 10.1186/s13756-019-0668-2.
  9. Kotb S, Lyman M, Ismail G, Abd El Fattah M, Girgis SA, Etman A, et al. Epidemiology of Carbapenem-resistant Enterobacteriaceae in Egyptian intensive care units using National Healthcare-associated Infections Surveillance Data, 2011-2017. Antimicrob Resist Infect Control 2020;9(1):2. DOI: 10.1186/s13756-019-0639-7.
  10. Nicolas-Chanoine MH, Vigan M, Laouénan C, Robert J; “E-carb Study Group”. Risk factors for carbapenem-resistant Enterobacteriaceae infections: A French case-control-control study. Eur J Clin Microbiol Infect Dis 2019;38(2):383–393. DOI: 10.1007/s10096-018-3438-9.
  11. Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol 2016;37(10):1219–1225. DOI: 10.1017/ice.2016.153.
  12. Ahn JY, Ahn SM, Kim JH, Jeong SJ, Ku NS, Choi JY, et al. Clinical characteristics and associated factors for mortality in patients with carbapenem-resistant Enterobacteriaceae bloodstream infection. Microorganisms 2023;11(5):1121. DOI: 10.3390/microorganisms11051121.
  13. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing, 32nd edition. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2022.
  14. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011;70(1):119–123. DOI: 10.1016/j.diagmicrobio.2010.12.002.
  15. Dawson B, Trapp RG. Basic and Clinical Biostatistics, 4th edition. New York: McGraw-Hill Professional; 2004. pp. 438–438. EISBN13: 9780071781329.
  16. CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019.
  17. Amer WH, Khalil HS, Abd EL, Wahab MA. Risk factors, phenotypic and genotypic characterization of carbapenem resistant Enterobacteriaceae in Tanta University Hospitals, Egypt. Int J Infect Control 2016;12(2). DOI: 10. 3396/ijic.v12i2.15905.
  18. El-Gazzar AM, Matta AM, Fouad NA, Azab MS. Phenotypic and genotypic detection of Klebsiella pneumoniae carbapenemase and New Delhi metallo-β-lactamase of Enterobacterales in Benha University Hospitals. Egypt J Med Microbiol 2016;25:19–24. DOI: 10.12816/0036805.
  19. El Defrawy I, Salem D, Ali G, Gamal D, Dabaa EE, Diab M, et al. Carbapenemase producing Enterobacterales clinical isolates from a tertiary care hospital in Egypt. Beni-Suef Univ J Basic Appl Sci 2023;12:98. DOI: 10.1186/s43088-023-00437-x.
  20. Ali A, Mohamed T. Detection and characterization of carbapenem resistant Enterobacteriaceae in Sohag University Hospitals. Eur Respir J 2019;54:PA2905. DOI: 10.1183/13993003.congress-2019. PA2905.
  21. Raheel A, Azab H, Hessam W, Abbadi S, Ezzat A. Detection of carbapenemase enzymes and genes among carbapenem-resistant Enterobacteriaceae isolates in Suez Canal University Hospitals in Ismailia, Egypt. Microb Infect Dis 2020;1(1):24–33. DOI: 10.21608/mid.2020.25702.1007.
  22. Zowawi HM, Sartor AL, Balkhy HH, Walsh TR, Al Johani SM, AlJindan RY et al. 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;58:3085–3090. DOI: 10.1128/aac.02050-13.
  23. Mathlouthi N, Al-Bayssari C, El Salabi A, Bakour S, Gwierif SB, Zorgani AA et al. Carbapenemases and extended-spectrum β-lactamases producing Enterobacteriaceae isolated from Tunisian and Libyan hospitals. J Infect Dev Ctries 2016;10(07):718–727. DOI: 10.3855/jidc.7426.
  24. Xu Y, Gu B, Huang M, Liu H, Xu T, Xia W, et al. Epidemiology of carbapenem resistant Enterobacteriaceae (CRE) during 2000-2012 in Asia. J Thorac Dis 2015;7(3):376–385. DOI: 10.3978/j.issn.2072-1439.2014.12.33. PMID: 25922715.
  25. Mitgang EA, Hartley DM, Malchione MD, Koch M, Goodman JL. Review and mapping of carbapenem-resistant Enterobacterales in Africa: Using diverse data to inform surveillance gaps. Int J Antimicrob Agents 2018;52(3):372–384. DOI: 10.1016/j.ijantimicag.2018. 05.019.
  26. Ssekatawa K, Byarugaba DK, Wampande E, Ejobi F. A systematic review: The current status of carbapenem resistance in East Africa. BMC Res Notes 2018;11(1):629. DOI: 10.1186/s13104-018-3738-2.
  27. El-Kholy AA, Girgis SA, Shetta MAF, Abdel-Hamid D, Elmanakhly A. Molecular characterization of multidrug-resistant Gram-negative pathogens in three tertiary hospitals in Cairo, Egypt. Eur J Clin Microbiol Infect Dis 2020;39:987–992. DOI: 10.1007/s10096-020-03812-z.
  28. Al Khamis M, AlMusa Z, Hashhoush M, Alsaif N, Salam A, Atta M. Carbapenem-resistant Enterobacteriaceae: A retrospective review of presentation, treatment, and clinical outcomes in a tertiary care referral hospital. Cureus 2022;14(7):e27094. DOI: 10.7759/cureus.27094.
  29. Kishk RM, Azab M, Hassan R, Dessouki O. Molecular Detection of bla OXA-48 carbapenemase in uropathogenic Klebsiella pneumoniae strains from Suez Canal University Hospital. EJMM 2019;28(3):71–77. DOI: 10.21608/EJMM.2019.283029.
  30. Shaker O, Gomaa H, ElMasry S, Abdel Halim R, Abdelrahman A, Kamal J. Evaluation of combined use of temocillin disk and mastdisks inhibitor combination set against polymerase chain reaction for detection of carbapenem-resistant Enterobacteriaceae. Maced J Med Sci 2018;6(2):242–247. DOI: 10. 3889/oamjms.2018.090.
  31. Shawky AM, Tolba TM, Hamouda HM. Emergence of New Delhi metallo beta lactamase blaNDM-1 and oxacillinases blaOXA-48 Producing Klebsiella pneumoniae in an Egyptian hospital. Egypt J Microbiol 2019;54:25–37. DOI: 10.21608/ejm.2019.12395.1096.
  32. El-Kholy A, El-Mahallawy HA, Elsharnouby N, Abdel Aziz M, Helmy AM, Kotb R. Landscape of multidrug-resistant gram-negative infections in Egypt: Survey and literature review. Infect Drug Resist 2021;24(14):1905–1920. DOI: 10.2147/idr.s298920.
  33. Lee HJ, Choi JK, Cho SY, Kim SH, Park SH, Choi SM, et al. Carbapenem-resistant Enterobacteriaceae: Prevalence and risk factors in a single community-based Hospital in Korea. Infect Chemother 2016; 48(3):166–173. DOI: 10.3947/ic.2016.48.3.166. Epub 2016 Sep 8. Erratum in: Infect Chemother 2019;51(4):435–438.
  34. Yeonju L, Kang JE, Ham JY, Lee JG, Rhie SJ. Risk factors of carbapenem-resistant Enterobacteriaceae acquisition at a community-based Hospital. Korean J Clin Pharm 2020;30(2):120–126. DOI: 10.24304/kjcp.2020.30.2.120.
  35. Pérez-Galera S, Bravo-Ferrer JM, Paniagua M, Kostyanev T, de Kraker MEA, Feifel J, et al. Risk factors for infections caused by carbapenem-resistant Enterobacterales: An international matched case-control-control study (EURECA). E Clin Med 2023;57:101871. DOI: 10.1016/j.eclinm.2023.101871.
  36. Zawawi RD, Ramli R, Sidik TM, Naina-Mohamed I, Loon LC. Clinical characteristics and risk factors of carbapenem-resistant Enterobacteriaceae: A case-control study in a tertiary hospital in Malaysia. Mal J Med Health Sci 2021;17(4):189–195(eISSN 2636-9346) Available from: https://medic.upm.edu.my/upload/dokumen/2021100809531427_MJMHS_0166.pdf.
  37. Zilberberg MD, Nathanson BH, Sulham K, Fan W, Shorr AF. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis. BMC Infect Dis 2017; 17(1):279. DOI: 10.1186/s12879-017-2383-z.
  38. Guo CH, Liu YQ, Li Y, Duan XX, Yang TY, Li FY, et al. High prevalence and genomic characteristics of carbapenem-resistant Enterobacterales and colistin-resistant Enterobacteriaceae from large-scale rivers in China. Environ Pollut 2023;331(Pt 2):121869. DOI: 10.1016/j.envpol.2023.121869.
  39. Zheng X, Wang JF, Xu WL, Xu J, Hu J. Clinical and molecular characteristics, risk factors and outcomes of Carbapenem-resistant Klebsiella pneumoniae bloodstream infections in the intensive care unit. Antimicrob Resist Infect Control 2017;6:102. DOI: 10.1186/s13756-017-0256-2.
  40. Ahmed TM, Afifi SA, Ateya RM. Prevalence and characterization of carbapenem-resistant Klebsiella pneumoniae isolated from the intensive care units of Zagazig University Hospitals. EJHM 2023;92(1):5540–5545. DOI: 10.21608/ejhm.2023.306163.
  41. Bartsch SM, McKinnell JA, Mueller LE, Miller LG, Gohil SK, Huang SS, et al. Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Clin Microbiol Infect 2017;23(1):48.e9–48.e16. DOI: 10.1016/j.cmi.2016.09.003.
  42. Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: Importance of combination therapy. Clin Infect Dis 2012;55(7):943–950. DOI: 10.1093/cid/cis588.
  43. Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR, et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): A retrospective cohort study. Lancet Infect Dis 2017;17(7):726–734. DOI: 10.1016/S1473-3099(17)30228-1.
  44. Demiraslan H, Dinc G, Ahmed SS, Elmali F, Metan G, Alp E, et al. Carbapenem-resistant Klebsiella pneumoniae sepsis in corticosteroid receipt mice: Tigecycline or colistin monotherapy versus tigecycline/colistin combination. J Chemother 2014; 26(5):276–281. DOI: 10.1179/1973947813Y.0000000143. PMID: 24070112.
  45. Ghosh S. Polymyxin B plus aerosolized colistin vs polymyxin B alone in hospital-acquired pneumonia (“AEROCOL” Study): A feasibility study. Indian J Crit Care Med 2024;28(8):792–795. DOI: 10.5005/jp-journals-10071-24767.
  46. Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin monotherapy vs. combination therapy for the treatment of multidrug-resistant infections: A systematic review and meta-analysis. Indian J Crit Care Med 2021;25(2):199–206. DOI: 10.5005/jp-journals-10071-23720.
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