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Transcript
Antimicrobial Resistant
Enterobacteriaceae
Educational Slide Set
HPSC
October 2014
Presentation Outline
1. What are Enterobacteriaceae?
2. What do we mean by the term ‘antimicrobial resistant
Enterobacteriaceae’?
3. What do we know about antimicrobial resistant
Enterobacteriaceae in Ireland & Europe?
4. Why is this important?
5. How can we help prevent the spread of antimicrobial
resistant Enterobacteriaceae?
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
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)
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)
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)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
What are β lactams?
•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
β lactam ring
β lactam ring
•Penicillin
•Amoxicillin
•Flucloxacillin
•Piperacillin-tazobactam
•Co-amoxiclav
•Cefuroxime
3rd generation
cephalosporins:
•Cefotaxime
•Ceftriaxone
•Ceftazidime
•Aztreonam
(acts on Gram-negative
aerobic bacteria only)
•Meropenem
•Ertapenem
β lactam ring
β lactams bind to proteins on the bacterial cell wall and kill bacteria by disrupting cell wall synthesis
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)
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
Extendedspectrum
β lactamases
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
Carbapenemases
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)
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)
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)
What does this mean for a patient with infection?
•
Microbiology laboratory report for
a patient who developed a wound
infection caused by a MDREnterobacteriaceae, called
Klebsiella pneumoniae
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)
AGENT
RESULT
Amoxicillin
RESISTANT
Co-amoxiclav
RESISTANT
Cefuroxime
RESISTANT
Cefotaxime
RESISTANT
Ceftazidime
RESISTANT
Piperacillin/tazobactam
RESISTANT
Aztreonam
RESISTANT
Meropenem
RESISTANT
Ciprofloxacin
RESISTANT
Gentamicin
SUSCEPTIBLE
Tobramycin
RESISTANT
Amikacin
RESISTANT
Tigecycline
RESISTANT
Colistin
SUSCEPTIBLE
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)
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)
BSI caused by Enterobacteriaceae: Ireland
Number of cases of E. coli BSI
2010
2011
2012
2013
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
326
% of K. pneumoniae BSI that were ESBL 5
positive
5.6
8.8
18.4
% of K. pneumoniae BSI that were MDR
3.2
5.2
11.7
2.2
Source: HPSC EARS-Net data
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
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)
CRE in Ireland
Number of confirmed
carbapenemase
producing (CRE) cases
Data source
2011
39
HPSC enhanced CRE
surveillance
2012
32
HPSC enhanced CRE
surveillance
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)
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)
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)
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)
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)
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)
Who might be ‘at-risk’ of carrying resistant
Enterobacteriaceae?
1. Patient with prior history of carriage or infection
2. Patient who has been in close contact with a patient
diagnosed as being a carrier (e.g., sharing a room or
toilet)
3. Patient transferred back to Ireland from foreign
healthcare facility (includes Northern Ireland)
4. Patient transferred from another healthcare facility in
Ireland: acute hospital or long term care facility
5. Patient admitted to a specialist care area: critical care
unit, haematology, oncology, transplant ward
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
How can we help prevent spread of antimicrobial
resistant Enterobacteriaceae?
1. Consistent hand hygiene during patient/resident care by
all healthcare professionals
2. Look after wounds and medical devices (e.g., drips,
catheters) and remove devices as soon as no longer
required
3. 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)
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)
How can we help prevent spread of antimicrobial
resistant Enterobacteriaceae?
1.
2.
3.
4.
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 transmissionbased 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)
Thank you for your attention
Further information available on HPSC website:
Antimicrobial Resistant Enterobacteriaceae: Educational Slideset (HPSC 2014)