Video:Carbapenem-resistant enterobacteriaceae

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Carbapenem-resistant enterobacteriaceae (Tutorial)
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Description

Carbapenem-resistant Enterobacteriaceae are drugs of last resort for such infections. They are resistant because they produce an commensals and infectious agents. The bacteria can kill up to half of patients who get bloodstream infections.[1][2] Several antimicrobial drugs have been tested for the effective treatment of CRE, 90 percent of bacterial isolates are susceptible to fosfomycin.[3][4][5]

Presentation

In terms of the presentation, we find that the location of the infection determines the symptoms. In pneumonia (lungs) you would find: cough,fever, shortness of breath and nausea.[6][3]

Complications

Among the possible complications of Carbapenem-resistant enterobacteriaceae are the following:kidney infection, lung abscess and sepsis.[7]

Cause 1

Three major classes of enzymes are involved in carbapenem resistance:[3] class A carbapenemases, class B metallo-Beta-lactamases (MBL), and class D Beta-lactamases (OXA). The four known groups of class A carbapenemases are: SME , IMI , GES , and KPC .[8] At the UVA Medical Center, a transfer mechanism of KPC-dependent carbapenem resistance was discovered in the transmission of a plasmid carrying the transposon (Tn4401), which contains the KPC gene, to several bacteria including Enterobacter cloacae, Klebsiella oxytoca, E. coli, and Citrobacter freundii.[9]

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Cause 2

Class B metallo-Beta-lactamases are found largely in Gram-negative bacteria and environmental bacteria. The subclasses of MBL enzymes are B1, B2, and B3. MBLs have diverse enzymatic functions and have the ability to hydrolyze Beta-lactam antibiotics.[3]

Cause 3

Class D Beta-lactamases, which hydrolyze oxacillin, provide a good example of the variety of ways that can be used to transfer resistance. The blaOXA genes which encode OXA Beta-lactamases are found on both chromosomes and plasmids, and they have their natural reservoir in environmental bacteria and deep-sea microflora. Insertions in the vicinity of these genes have been shown to increase the strength of their promoters and increase resistance. Because of these characteristics, a wide geographic dissemination of OXA carbapenemase resistance in particular has occurred.[8]

Risk factors

Hospitals are primary transmission sites for CRE-based infections. Up to 75 percent of hospital admissions attributed to CRE were from long-term care facilities or from another hospital.[10]

Mechanism 1

In general, carbapenem, a Beta-lactam antibiotic, targets cells by inhibiting transpeptidases. This prevents synthesis of peptidoglycan, a necessary structural component, leading to cell lysis. Resistance to carbapenem among Gram-negative bacteria in general can be acquired through several mechanisms.[11][12] On such mechanism is the active transport of carbapenem drugs out of the cell, augmented drug efflux, which has been observed in some resistant species.[11][13]

Mechanism 2

Another mechanism of resistance is mutation in or loss of outer membrane porins, preventing antibiotics from entering the cells.[14] Changes within the porin protein gene cause a frameshift, altering the porin structure and function.[14] Changes in the porin protein hinder the diffusion of carbapenem and other antibiotics into the periplasm.[15]

Mechanism 3

CRE produce carbapenemases, a form of β-lactamase.[16] These enzymes cleave the β-lactam ring, an essential component of β-lactam antibiotics that are recognized by and bound to PBPs. Carbapenemases are divided into different classes, depending on the structure of the enzyme and the mechanism by which they hydrolyze the β-lactam ring. [17][18][19]

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References

  1. ↑ Gall, Elizabeth; Long, Anna (March 2020). "Carbapenem-Resistant Enterobacteriaceae". Making Healthcare Safer III: A Critical Analysis of Existing and Emerging Patient Safety Practices [Internet]. Agency for Healthcare Research and Quality (US).
  2. ↑ "CDC: Action needed now to halt spread of deadly bacteria: Data show more inpatients suffering infections from bacteria resistant to all or nearly all antibiotics" (Press release). The Centers for Disease Control. March 5, 2013. Archived from the original on December 20, 2017. Retrieved March 5, 2013. During just the first half of 2012, almost 200 hospitals and long-term acute-care facilities treated at least one patient infected with these bacteria.
  3. ↑ 3.0 3.1 3.2 3.3 Sattar, Saud Bin Abdul; Nguyen, Andrew D.; Sharma, Sandeep (2024). "Bacterial Pneumonia". StatPearls. StatPearls Publishing.
  4. ↑ Morrill, Haley J.; Pogue, Jason M.; Kaye, Keith S.; LaPlante, Kerry L. (5 May 2015). "Treatment Options for Carbapenem-Resistant Enterobacteriaceae Infections". Open Forum Infectious Diseases. 2 (2): ofv050. doi:10.1093/ofid/ofv050. ISSN 2328-8957. Archived from the original on 25 February 2024. Retrieved 13 September 2024.
  5. ↑ Falagas, Matthew E; Kastoris, Antonia C; Kapaskelis, Anastasios M; Karageorgopoulos, Drosos E (January 2010). "Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum β-lactamase producing, Enterobacteriaceae infections: a systematic review". The Lancet Infectious Diseases. 10 (1): 43–50. doi:10.1016/S1473-3099(09)70325-1.
  6. ↑ "About Carbapenem-resistant Enterobacterales". Enterobacterales (carbapenem-resistance). 14 May 2024. Archived from the original on 10 August 2024. Retrieved 2 September 2024.
  7. ↑ Bandick, Rasmus G.; Mousavi, Soraya; Bereswill, Stefan; Heimesaat, Markus M. (17 September 2020). "Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae". European Journal of Microbiology and Immunology. 10 (3): 115–124. doi:10.1556/1886.2020.00022.
  8. ↑ 8.0 8.1 Pfeifer, Yvonne; Cullik, Angela; Witte, Wolfgang (1 August 2010). "Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens". International Journal of Medical Microbiology. 300 (6): 371–379. doi:10.1016/j.ijmm.2010.04.005. ISSN 1438-4221. Retrieved 29 September 2024.
  9. ↑ Mathers, AJ; Cox, HL; Kitchel, B; Bonatti, H; Brassinga, AK; Carroll, J; Scheld, WM; Hazen, KC; Sifri, CD (2011). "Molecular Dissection of an Outbreak of Carbapenem-Resistant Enterobacteriaceae Reveals Intergenus KPC Carbapenemase Transmission through a Promiscuous Plasmid". mBio. 2 (6): e00204–11. doi:10.1128/mBio.00204-11. PMC 3202755. PMID 22045989.
  10. ↑ Perez, F; Van Duin, D (2013). "Carbapenem-resistant Enterobacteriaceae: A menace to our most vulnerable patients". Cleveland Clinic Journal of Medicine. 80 (4): 225–33. doi:10.3949/ccjm.80a.12182. PMC 3960994. PMID 23547093.
  11. ↑ 11.0 11.1 Suay-García, Beatriz; Pérez-Gracia, María Teresa (19 August 2019). "Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections". Antibiotics (Basel, Switzerland). 8 (3): 122. doi:10.3390/antibiotics8030122. ISSN 2079-6382. Archived from the original on 26 August 2024. Retrieved 15 September 2024.
  12. ↑ Armstrong, Tom; Fenn, Samuel Jacob; Hardie, Kim R. (2021). "JMM Profile: Carbapenems: a broad-spectrum antibiotic". Journal of Medical Microbiology. 70 (12). doi:10.1099/jmm.0.001462. Archived from the original on 20 September 2024. Retrieved 18 September 2024.
  13. ↑ Papp-Wallace, Krisztina M.; Endimiani, Andrea; Taracila, Magdalena A.; Bonomo, Robert A. (November 2011). "Carbapenems: Past, Present, and Future". Antimicrobial Agents and Chemotherapy. 55 (11): 4943–4960. doi:10.1128/AAC.00296-11. ISSN 0066-4804. Archived from the original on 2024-09-20. Retrieved 2024-09-20.
  14. ↑ 14.0 14.1 Little, ML; Qin, X; Zerr, DM; Weissman, SJ (2012). "Molecular diversity in mechanisms of carbapenem resistance in paediatric Enterobacteriaceae". International Journal of Antimicrobial Agents. 39 (1): 52–57. doi:10.1016/j.ijantimicag.2011.09.014. PMC 3237943. PMID 22055532.
  15. ↑ Logan, LK (2012). "Carbapenem-resistant enterobacteriaceae: an emerging problem in children". Clinical Infectious Diseases. 55 (6): 852–859. doi:10.1093/cid/cis543. PMID 22700827.
  16. ↑ Shin, So Youn; Bae, Il Kwon; Kim, Juwon; Jeong, Seok Hoon; Yong, Dongeun; Kim, June Myung; Lee, Kyungwon (2012). "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. 61 (2): 239–245. doi:10.1099/jmm.0.037036-0. ISSN 1473-5644.
  17. ↑ Nordmann, Patrice; et al. (May 2012). "Carbapenem resistance in Enterobacteriaceae: here is the storm!". Trends in Molecular Medicine. 18 (5): 263–272. doi:10.1016/j.molmed.2012.03.003. PMID 22480775.
  18. ↑ Queenan, Anne Marie; Karen Bush (July 2007). "Carbapenemases: the Versatile β-Lactamases". Clinical Microbiology Reviews. 20 (3): 440–458. doi:10.1128/CMR.00001-07. PMC 1932750. PMID 17630334.
  19. ↑ Patel, Gopi; Bonomo (March 2013). ""Stormy waters ahead": global emergence of carbapenemases". Frontiers in Microbiology. 4: 48. doi:10.3389/fmicb.2013.00048. PMC 3596785. PMID 23504089.
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