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CP-CRE and the non-KPCs

CP-CRE and the non-KPCs. DJ Shannon, MPH Antimicrobial Resistance Epidemiologist Infectious Disease Epidemiology Epidemiology Resource Center Indiana State Department of Health. Overview. Definitions Review of antibiotic resistance CRE and CP-CRE CP-CRE data

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CP-CRE and the non-KPCs

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  1. CP-CRE and the non-KPCs DJ Shannon, MPH Antimicrobial Resistance Epidemiologist Infectious Disease Epidemiology Epidemiology Resource Center Indiana State Department of Health

  2. Overview • Definitions • Review of antibiotic resistance • CRE and CP-CRE • CP-CRE data • A closer look at the non-KPCs • Colonization screening overview

  3. Definitions • Multidrug-resistant organism (MDRO): an organism that is resistant to one or more agent in at least three classes of antibiotics – or that exhibits a classification of resistance that is of epidemiological concern (e.g. MRSA, VRE, ESBL, CRE) • Extensively drug-resistant organism (XDRO): microorganisms that are resistant to nearly all antimicrobial agents that would be considered for treatment • Pandrug-resistant organism (PDRO): microorganisms that are resistant to all antimicrobial agents that would be considered for treatment

  4. Mechanisms of Antibiotic Resistance • Antibiotic target changes • Porinmutations • Efflux pumps • Enzymatic inhibition

  5. Mechanisms of Antibiotic Resistance

  6. Antibiotic Target Changes • Bacteria can change a site that an antibiotic would normally target • This can quickly lead to resistance bacterial populations • Example: • Penicillin-binding protein modification

  7. Porin Mutations Porins are found in the outer membrane of Gram-negative bacteria Porins help transport material in and out of the cell Mutations, often a reduction in porin production, can cause resistance to antibiotics

  8. Efflux Pumps • A very efficient mechanism of antibiotic resistance • Efflux pumps actively remove antibiotics from within the cell wall • Certain types of efflux pumps can cause multidrug-resistance • Example: Efflux pumps found in Pseudomonas aerugionsa

  9. Enzymatic Inhibition • The most common mechanism of antibiotic resistance • Enzymes produced by bacteria can inactivate the antibiotic • ß-lactamases • Penicillinases • AmpCcephalosporinases • Extended-spectrum ß-lactamases (ESBL) • Carbapenemases

  10. Mobility of Carbapenemases

  11. Carbapenemases • KPC: Klebsiella pneumoniae carbapenemase • Most common in the United States • NDM: New Delhi Metallo-ß-lactamase • Most common in India • IMP: Imipenemase • Most common in Japan • VIM: Verona Integron-mediated Metallo-ß- lactamase • Most common in western Europe • OXA-48: Oxacillinase-48 • Most common in Mediterranean countries

  12. CRE: A Public Health Threat • CRE in the United States are an urgent threat • CRE infections are associated with high mortality rates • CRE confer high levels of resistance • CP-CRE have very mobile resistance genes that can easily be shared with other organisms (CPOs)

  13. Carbapenem-Resistant Enterobacteriaceae • Definition: Any Enterobacteriaceae that are not susceptible (i.e. intermediate or resistant) to a carbapenem antibiotic

  14. Carbapenem-Resistant Enterobacteriaceae • Enterobacteriaceae can be resistant to carbapenems through several resistance mechanisms • Carbapenemase productionis currently the most concerning

  15. Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae • Enterobacteriaceae isolates that demonstrate carbapenemase production via one of the following: • Positive for carbapenemase production by a phenotypic test (e.g., Carba NP, mCIM) • Positive for a carbapenemase gene marker

  16. CRE vs. CP-CRE CP-CRE !!! + ESBL Reportable

  17. Indiana CP-CRE Cases, 2016-2018 Total: 294 Total: 230 Total: 355 2018 2016 2017 Cases Average: 28 Month *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  18. State: 879 Indiana CP-CRE Cases by District, 2016-2018 District 1: 380 District 2: 30 District 3: 70 District 4: 19 District 5: 200 District 6: 90 District 7: 51 District 8: 17 District 9: 17 District 10: 5 *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  19. Indiana CP-CRE Cases, 2016-2018 879 CP-CRE cases Organisms • 664 Klebsiella pneumoniae • 70 Serratia marcescens • 53 Escherichia coli • 42 Enterobacter cloacae complex • 19 Citrobacter freundii complex • 15 Klebsiella oxytoca • 6 Citrobacter koseri • 4 Proteus mirabilis • 2 Klebsiella aerogenes • 2 Providencia rettgeri • 1 Klebsiella ozaenae • 1 Klebsiella variicola • 1 Leclercia adecarboxylata • 1 Morganella morganii Mechanisms • 804 KPC • 22 NDM • 18 VIM • 9 OXA-48-like • 2 IMP • 24 unknown *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  20. A Closer Look at the non-KPCs IMP: Imipenemase NDM: New Delhi Metallo- ß-lactamase VIM: Verona Integron-mediated Metallo-ß-lactamase • Most clinically threatening • More resistant • More mobile • Fewer antibiotics

  21. Indiana NDM cases by healthcare facility, 2016-2018 *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  22. Indiana VIM cases by healthcare facility, 2016-2018 *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  23. Indiana IMP cases by healthcare facility, 2016-2018 *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  24. A Closer Look at the non-KPCs OXA-48: Oxacillinase-48 • Less resistant* • Difficult to detect • *Unless other mechanism present

  25. Indiana OXA cases by healthcare facility, 2016-2018 *Preliminary 2018 data represents 1/1/2018 – 7/31/2018

  26. AST Profile Cheat Sheet CP-CRE bonus: If Aztreonam is resistant, think KPC – not NDM/VIM/IMP

  27. Infection Prevention Implications Healthcare Personnel Education Containment Hand hygiene Contact precautions Cohorting of residents and staff Environmental cleaning Chlorhexidine bathing • Identification • Laboratory notification • Inter-facility communication • Screening contacts of CRE patients • Active surveillance for CRE colonization • Prevention • Careful use of invasive medical devices • Antibiotic Stewardship

  28. Antibiotic Resistance Laboratory Network

  29. Response Tiers • Tier 1: Novel resistance, rare resistant organisms or pandrug-resistant organisms • Example: Candida auris • Tier 2: Known, yet uncommon, resistance mechanisms • Example: VIM-producing Enterobacteriaceae • Tier 3: Targeted, non-endemic resistance mechanism • Example: KPC-producing Enterobacteriaceae

  30. Response Tiers Photo Source: CDC

  31. What happens after colonization screening? • Contact precautions use • Indefinite use for CP-CRE • See SHEA Guidelines • Retesting • When a negative isn’t really a negative… • Patient and staff cohorting as needed • Sharing isn’t caring • To treat or not to treat?

  32. Resources Facility Guidance for Control of CRE

  33. Resources Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006

  34. Resources SHEA Expert Guidance for the Duration of Contact Precautions for Acute-Care Settings

  35. Contact Information DJ Shannon, MPH Antimicrobial Resistance Epidemiologist Infectious Disease Epidemiology Epidemiology Resource Center Indiana State Department of Health Work: 317-233-1306 Email: dshannon1@isdh.in.gov

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