1. Antimicrobial Resistant Enterobacteriaceae
Educational Slide Set
HPSC
October 2014

2. Presentation Outline What are Enterobacteriaceae?
What do we mean by the term ‘antimicrobial resistant Enterobacteriaceae’?
What do we know about antimicrobial resistant Enterobacteriaceae in Ireland & Europe?
Why is this important?
How can we help prevent the spread of antimicrobial resistant Enterobacteriaceae?
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

3. What are Enterobacteriaceae?
A collective term used to describe many of the different types of bacteria, which are normally found in the gut/bowel/enteric tract:
E. coli
Klebsiella spp.
Proteus mirabilis
Enterobacter cloacae
Their presence mostly represents a state of ‘carriage’/colonisation’
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

4. Enterobacteriaceae
In a vulnerable person, they can cause infection: e.g., presence of wound, invasive device, critical illness, immunocompromise
Common causes of community-acquired and healthcare-associated infections (HCAI):
Urinary tract infections (UTI) – cystitis, pyelonephritis
Wound and surgical site infections
Healthcare-associated pneumonia
Bloodstream infections (BSI)
Septic shock
Potentially fatal infections in vulnerable patients
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

5. How do we treat infections caused by Enterobacteriaceae?
Sometimes the immune system can’t control infection on its own: ANTIMICROBIALS may be needed to kill the Enterobacteriaceae
Three major antimicrobial classes are commonly used for treating infections caused by Enterobacteriaceae:
Beta (β) lactams
Fluoroquinolones – ciprofloxacin, ofloxacin
Aminoglycosides – gentamicin, tobramycin, amikacin
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

6. What are β lactams? Penicillin Amoxicillin Flucloxacillin
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
What are β lactams?
Penicillin
Amoxicillin
Flucloxacillin
Piperacillin-tazobactam
Co-amoxiclav
A large family of antimicrobials
sharing the common property of a
β lactam ring
Over the years, more sophisticated
types of β lactams developed to
overcome bacteria developing
resistance to each type
No new types of β lactams developed
in recent decades and no new types
expected to be available in the next
decade
β lactam ring
Cefuroxime
3rd generation
cephalosporins:
Cefotaxime
Ceftriaxone
Ceftazidime
β lactam ring
Aztreonam
(acts on Gram-negative
aerobic bacteria only)
β lactam ring
Meropenem
Ertapenem
β lactam ring
β lactams bind to proteins on the bacterial cell wall and kill bacteria by disrupting cell wall synthesis

7. What are carbapenems?
A group of powerful “last resort” β lactam antimicrobials (e.g., meropenem)
Carbapenems must be reserved for treatment of:
Severe infection in critically ill patients
Infections caused by Enterobacteriaceae with resistance to other antimicrobial classes
Carbapenems should generally only be prescribed on the advice of an infection specialist: clinical microbiologist or infectious diseases physician
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

8. How do Enterobacteriaceae become resistant to β lactams?
Enterobacteriaceae acquire the gene to produce enzymes ‘β lactamases’ which destroy β lactam antimicrobials
The more powerful the β lactamase enzyme, the more types of β lactam antimicrobial it can destroy
Penicillinases
Extended-spectrum
β lactamases
Carbapenemases
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

9. What are ESBLs? Extended Spectrum β Lactamases
Enzymes produced by Enterobacteriaceae, which destroy most β lactams, including 3rd generation cephalosporins
The remaining β lactam which is reliable for treating ESBL infection is a carbapenem (e.g., meropenem)
The gene for making ESBLs is carried on mobile genes (plasmids), which are easily swapped between different types of Enterobacteriaceae
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

10. What are carbapenemases?
Even more broadly-acting enzymes produced by Enterobacteriaceae, which destroy VIRTUALLY ALL β lactams, including carbapenems
This leaves few antimicrobials available to treat infection caused by these bacteria
The gene for making carbapenemases is also easily swapped between different types of Enterobacteriaceae
Also known as carbapenemase-producing or carbapenem resistant Enterobacteriaceae ‘CRE’
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

11. What do we mean by multi-drug resistant (MDR) Enterobacteriaceae?
Term used when Enterobacteriaceae have become resistant to at least two different antimicrobial classes:
Resistant to β lactams mainly due to production of either ESBLs and/or carbapenemases
AND
Resistant to a fluoroquinolone (e.g., ciprofloxacin)
AND/OR
Resistant to an aminoglycoside (e.g., gentamicin)
There are extremely limited treatment options for infection caused by MDR-Enterobacteriaceae
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

12. What does this mean for a patient with infection?
Microbiology laboratory report for a patient who developed a wound infection caused by a MDR-Enterobacteriaceae, called Klebsiella pneumoniae
AGENT
RESULT
Amoxicillin
RESISTANT
Co-amoxiclav
Cefuroxime
Cefotaxime
Ceftazidime
Piperacillin/tazobactam
Aztreonam
Meropenem
Ciprofloxacin
Gentamicin
SUSCEPTIBLE
Tobramycin
Amikacin
Tigecycline
Colistin
Resistant to all the β lactams: including 3rd generation
cephalosporins (ESBL production) & carbapenem
(carbapenemase production = CRE)
ALSO resistant to a fluoroquinolone – ciprofloxacin
ALSO resistant to some aminoglycosides –
tobramycin & amikacin
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

13. What does this mean for the patient?
Infection caused by antimicrobial resistant Enterobacteriaceae (e.g., ESBL or CRE) more likely to result in patient harm or death than if caused by antimicrobial susceptible bacteria
Why?
Patients with ESBL/CRE infections may already be very ill or vulnerable to infection
There could be a delay in detecting that infection is caused by ESBLs or CRE = delay in starting patient on optimal antimicrobial treatment
Infections more difficult to treat because very few suitable options available – risk of toxic side effects with some drugs
Longer hospital stay, longer recovery time, delayed return to normal life/work, increased cost to patient & healthcare system
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

14. The two commonest types of Enterobacteriaceae that cause BSI are:
What do we know about antimicrobial resistant Enterobacteriaceae in Ireland & Europe?
Information on one of the most significant infection types; bloodstream infection (BSI) is collected by every microbiology laboratory & reported to the HPSC
The two commonest types of Enterobacteriaceae that cause BSI are:
E. coli
Klebsiella pneumoniae
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

15. BSI caused by Enterobacteriaceae: Ireland
2010
2011
2012
2013
Number of cases of E. coli BSI
2170
2210
2449
2530
% of E. coli BSI that were ESBL positive
6.1
7.5
8.6
10.5
% of E. coli BSI that were MDR
11.7 13
13.5
14.8
Number of cases of Klebsiella pneumoniae BSI
326
312
345
% of K. pneumoniae BSI that were ESBL positive 5
5.6
8.8
18.4
% of K. pneumoniae BSI that were MDR
2.2
3.2
5.2
Source: HPSC EARS-Net data
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

16. Based on EARS-Net data to end Q1 2014, the percentage of E
Based on EARS-Net data to end Q1 2014, the percentage of E. coli BSI in Ireland that were resistant to 3rd generation cephalosporins was 12.2%. Therefore, Ireland’s colour on the European map has turned from light green (2004) to orange (Q1 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

17. Based on EARS-Net data to end Q1 2014, the percentage of Klebsiella pneumoniae BSI in Ireland that were resistant to 3rd generation cephalosporins was 13%. Therefore, Ireland’s colour on the European map has turned from yellow (2005) to orange (Q1 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

18. Based on EARS-Net data to end Q1 2014, the percentage of Klebsiella pneumoniae BSI in Ireland that were classified as multi-drug resistant was 7%. Therefore, Ireland’s colour on the European map has changed from dark green (2005) to yellow (Q1 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

19. Based on EARS-Net data to end Q1 2014, the percentage of Klebsiella pneumoniae BSI in Ireland that were resistant to carbapenems was 1%. Therefore, Ireland’s colour on the European map remains at green (Q1 2014). However, BSI represent the most severe and less common form of Klebsiella pneumoniae infection. These organisms are implicated in many other types of infection and also can be found as part of normal colonising flora
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

20. Carbapenemase producing Enterobacteriaceae (CPE or CRE) in Ireland
2009: CRE first detected in Ireland
March 2011: Laboratory detection of CRE became notifiable
September 2011: Invasive CRE infection added to updated Notifiable Infectious Disease Regulations
2011: CRE enhanced surveillance scheme launched
2012: National Carbapenemase Producing Enterobacteriaceae Reference Laboratory Service (CPEaRLS) established at GUH
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

21. CRE in Ireland Number of confirmed carbapenemase producing (CRE) cases
Data source
2011 39
HPSC enhanced CRE surveillance
2012 32
2013 48
CPEaRLS report
Data represents reference laboratory-confirmed cases of carbapenemase-producing
Enterobacteriaceae (CRE) from clinical (sterile and non-sterile sites)
& screening (rectal swab or faeces) specimens
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

22. What is the surveillance data telling us?
Monitoring antimicrobial resistance in Enterobacteriaceae in Ireland and Europe, shows a worrying increase, particularly in the past five years
ESBL, CRE and multi-drug resistant (MDR) Enterobacteriaceae are detected with increasing frequency in acute hospitals and long-term care facilities across Ireland
Patients and residents are frequently transferred between these settings
Antimicrobial use is a major driver of antimicrobial resistance
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

23. Do we use many antimicrobials in Ireland?
80% of antimicrobial use is in the community setting (primary & long-term care) and use is increasing
Residents of Irish long-term care facilities three times more likely to be prescribed an antimicrobial than their European counterparts
Sources: HPSC Antimicrobial Consumption Surveillance & ECDC HALT PPS 2010 & 2013
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

24. Do we use many antimicrobials in acute hospitals in Ireland?
Whilst overall acute hospital antimicrobial use has remained relatively stable, there has been a significant increase in carbapenem use in Ireland since 2007
Source: HPSC Acute Hospital Antimicrobial Consumption Surveillance
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

25. How do antimicrobial resistant Enterobacteriaceae spread?
Patient-to-patient OR resident-to-resident
Via contaminated environment, shared toilet facilities
Via hands of healthcare workers, patients/residents and visitors, where hand hygiene opportunities have not been taken
Hospital-to-hospital OR hospital-to-long-term care facility
Direct patient/resident transfer
Patients/residents attending more than one hospital
Country-to-country
Patients repatriated to Irish hospital following illness abroad
Health tourism
International travel – potential to acquire organisms via contaminated water or food
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

26. How would we know a person is carrying antimicrobial resistant Enterobacteriaceae?
Via a positive microbiology result:
Specimen taken to investigate suspected infection (e.g., urine, blood cultures, sputum, swab etc.)
Specimen taken to screen/check for bowel carriage (e.g., rectal swab or faeces)
Patient already known to be a carrier from a result obtained during a prior attendance OR from testing in another healthcare facility
Without a positive microbiology result, we would not know whether a person is a carrier:
Often asymptomatic bowel carriage and less often implicated as a cause of infection
Bowel is laden with Enterobacteriaceae: no proven method to eradicate bowel carriage and carriage often indefinite
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

27. Who might be ‘at-risk’ of carrying resistant Enterobacteriaceae?
Patient with prior history of carriage or infection
Patient who has been in close contact with a patient diagnosed as being a carrier (e.g., sharing a room or toilet)
Patient transferred back to Ireland from foreign healthcare facility (includes Northern Ireland)
Patient transferred from another healthcare facility in Ireland: acute hospital or long term care facility
Patient admitted to a specialist care area: critical care unit, haematology, oncology, transplant ward
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

28. How can we help prevent spread of antimicrobial resistant Enterobacteriaceae?
Consistent hand hygiene during patient/resident care by all healthcare professionals
Look after wounds and medical devices (e.g., drips, catheters) and remove devices as soon as no longer required
Prudent antimicrobial prescribing:
Follow local prescribing guidelines & use the antibiotic care bundle – right drug, dose, duration
Seek advice from clinical microbiologist/ID physician before prescribing carbapenems
1,2 & 3 FOR EVERY PATIENT/RESIDENT – EVERY TIME
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

29. Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

30. How can we help prevent spread of antimicrobial resistant Enterobacteriaceae?
Patients/residents who are already known to be carriers should be cared for using appropriate transmission-based precautions
Ensure good communication when patients/residents already known to be carriers are being transferred between clinical areas and between healthcare facilities
Use healthcare record alerts and electronic alerts to help staff identify patients/residents who are known to be carriers when they return to the hospital/long-term care facility
In the acute hospital setting, ‘at-risk’ patients for bowel carriage should be identified and cared for using appropriate transmission-based precautions, with use of screening specimens to detect bowel carriage, as per national and local laboratory testing guidelines
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)

31. Thank you for your attention
Further information available on HPSC website:
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)