Carbapenem-resistant
Enterobacteriacea
(ent-ə-rō-ˌbak-ˌtir-ē-ˈā-sē-ˌā)
July 2013
http://www.forvo.com/word/enterobacteriaceae/
Outline
• Background
• Epidemiology
• Control
2
What are Enterobacteriaceae?
• Family of Gram negative bacteria
– Normal part of the human gut bacteria
– Common causes of community and healthcare-associated
infections (HAIs)
– Most common are E. coli and Klebsiella species
• E. coli is the most common cause of outpatient urinary
tract infections.
• E. coli and Klebsiella species (especially K. pneumoniae)
are important causes of HAIs.
– Together, they accounted for 15% of all HAIs reported to the
CDC’s National Healthcare Safety Network (NHSN) in 2007.
4
Why have Enterobacteriacae become an issue?
• Some of these kinds of bacteria have become resistant to
most antibiotics. They are called Carbapenem-resistant
Enterobacteriaceae or “CRE”
• Infections with CRE germs are very difficult to treat and can
be deadly—one report cites they can contribute to death in
up to 50% of patients who become infected. (CDC)
• Beta-lactam class carbapenem antibiotics (antibiotics that
have been developed from penicillin) have been mainstay of
treatment for years
• However, resistance to carbapenem antibiotics emerged
several years ago and has continued to increase steeply.
– Extended spectrum β-lactamase producing Enterobacteriaceae
(ESBLs)
– Plasmid-mediated AmpC-type enzymes
5
The Last Line of Defense
• Fortunately, our most potent β-lactam class carbapenems
remained effective against almost all
Enterobacteriaceae...until recently…
Doripenem, Ertapenem, Imipenem, Meropenem
• Unfortunately, “Antimicrobial resistance follows
antimicrobial use as surely as night follows day”
~John Jernigan
6
How bad is it?
Map showing states where CRE has been identified
by the CDC.
First case in U.S. showed up in NC in 2001 !
How bad is it?
• About 4% of U.S. hospitals had at least one patient
with a CRE infection during the first-half of 2012.
• About 18% of long-term acute care hospitals had
one during this same timeframe.
• CRE germs kill up to half of patients who get
bloodstream infections from them.
• Untreatable and hard-to-treat infections from CRE
germs are on the rise among patients in medical
facilities.
• CRE germs have become resistant to all or nearly all
the antibiotics we have today.
Carbapenem resistance in
K. pneumoniae HAIs -NHSN
Time
CLABSI
CAUTI
VAP
2007-2008
11%
9%
4%
2009-2010
12.5%
12.8%
11.2%
SSI
7.9
A Klebsiella spp. was identified as the pathogen associated with 8% of CLABSIs, 11%
of CAUTIs, 10% of VAPs and 4% of SSIs in 2009-2010
Sievert et al. Infect Control Hosp Epidemiol 2013;34(1):1-14
Hidron, A et al Infect Control Hospital Epidemiol. 2008;29:996
8
CRE are epidemiologically important:
• CRE are associated with high mortality rates (up to
50% in some studies).
• In addition to β-lactam/carbapenem resistance, CRE
often carry genes that have high levels of resistance
to many other antimicrobial drugs, often leaving very
limited treatment options.
• CRE have spread throughout many parts of the U.S.
and have the potential to spread more widely.
• The emergence and spread of carbapenem
resistance among Enterobacteriaceae in the United
States represent a serious threat to public health.
How are CRE spread?
• To get a CRE infection, a person must be exposed
to CRE germs.
• CRE germs are usually spread person-to-person
through contact with infected or colonized
people, particularly contact with wounds or stool.
• CRE can cause infections when they enter the
body, often through medical devices like
ventilators, intravenous catheters, urinary
catheters, or wounds caused by injury or surgery.
Who is most likely to get a CRE infection?
• Patients who have been in a healthcare facility for a long
time (longer length-of-stay)
• Patients with long-term care facility (LTCF) exposure
• Patients who have been in ICU
• Patients who have received antibiotics
–
–
–
–
Carbapenems
Cephalosporins
Fluoroquinolones
Vancomycin
• Organ or stem cell transplant patients
• Patients with invasive medical devices such as Foley
catheters, central lines, G-tubes, ventilators, etc.
• Healthy people usually don’t get CRE infections.
Patel et al. ICHE 2008; 29:1099-106
Schwaber et al. Antimicrob Agents Cehmother 2008; 52:1028-33
Hussein et al. ICHE 2009; 30:666-71
11
Risk Factors for Getting CRE Infections
• Comorbidities:
– Diabetes
– Heart disease
– HIV
– Renal disease
– Liver disease
– Transplant
• Healthcare-associated factors:
– Presence of medical devices (Foleys, central lines, ventilators,
G-tube, tracheostomy, etc.)
– Being in ICU
– Prior and/or current antibiotics
– History of MDRO
– Decubitus ulcer
– Lower Braden Scale score
Prabaker et al. Infect Control Hosp Epidemiol 2012;33(12):1193-1199
Prior Antibiotics Increase Risk of CRE
CRKP
(n=99)
CSKP
(n=99)
p-value
Cephalosporins
63
31
p<0.001
Fluoroquinolones
36
23
p=0.05
B-lactam/inhibitor
54
33
p=0.005
Aminoglycosides
14
3
p=0.01
Carbapenems
54*
6
p<0.001
• *26 (48%) on carbapenems at time of isolation of CRKP
• *37 (69%) either on carbapenems or completed a
course of carbapenems within 2 weeks prior to CRKP
isolation
Patel et al. Infect Control Hosp Epidemiol 2008;29:1099-1106
13
Can CRE be treated?
• Many people with CRE will have the germ in or on
their body without it producing an infection.
These people are said to be colonized with CRE,
and they do not need antibiotics for the CRE.
• If the CRE are causing an infection, the antibiotics
that will work against it are limited but some
options are often available.
• Some infections might be able to be treated with
other therapies, like draining the infection.
• Strains that have been resistant to all antibiotics
are very rare but have been reported.
Control of CRE
• CRE can be spread from patients that are
infected or colonized.
• To prevent CRE spread, there are several
important things to do, called “prevention
strategies”.
• These prevention strategies apply to all
patients with CRE, whether they are infected
or colonized.
16
CDC Toolkit – An Important Resource
• http://www.cdc.gov/hai/organisms/cre/cretoolkit/
17
CRE Control: No Magic Bullet
but some Core Prevention Strategies from
the CDC
1.
2.
3.
4.
5.
6.
7.
8.
Lab identification/surveillance
Education
Hand hygiene
Contact Precautions with strict PPE compliance
Patient and staff cohorting
Limiting use of invasive devices
Surveillance screening
Antimicrobial stewardship
http://www.cdc.gov/HAI/organisms/cre/index.html
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Laboratory Notification
• <Provide your facility’s process for how and
when lab notifies IP, unit, and/or physician
about CRE.>
• <List steps to be taken by each group when lab
notifies them (e.g. place patient on Contact
Precautions, etc.)>
Surveillance
• <Insert facility CRE surveillance plan/protocol(s)>
Education
Staff in all settings who care for patients with
MDROs, including CRE, should be educated about
preventing transmission of these organisms. At a
minimum this should include:
– Proper use of Contact Precautions
– Hand hygiene
Don’t forget physicians, PAs, NPs, phlebotomists,
OT/PT, RT, transport personnel, EMT, housekeeping
staff, etc. AND – don’t forget the patient and visitors!
Hand Hygiene
• Strict hand hygiene by everyone is critical!
• Hand washing and use of alcohol hand rubs are both
effective with CRE.
• MONITOR hand hygiene compliance to make sure it’s being
done and report back to staff on a regular basis.
• Immediate feedback should be provided to anyone who
misses opportunities for hand hygiene.
• Ensure access to adequate hand hygiene stations (e.g.,
clean sinks and/or alcohol-based hand rubs) and ensure
they are well stocked with supplies (e.g. towels, soap, etc.)
and clear of clutter.
• Don’t forget to teach the patient and visitors about the
importance of hand hygiene and make sure they can get to
a sink/hand rub dispenser.
22
Contact Precautions
<Place your CP
sign here>
23
• <When to implement CP on CRE
patients – include patients that
are colonized as well as
infected>
• <Length of time patient should
be on CP per your facility policy
on CRE>
• <How patients may be removed
from CP>
Contact Precautions – Minimum
Requirements for <Your Facility>
• Perform hand hygiene <when and how per facility
policy>
• Don gown and gloves <when>
• Remove the gown and gloves and perform hand
hygiene prior to exiting the affected patient’s room
• <Include short tutorial on proper donning and removal
of PPE>
<Tip to presenter: Consider fun ways to teach PPE
application, such as having a volunteer don PPE properly,
dip hands in chocolate pudding, and remove w/o getting
pudding where it should not be. (Pudding is a visual
surrogate for germs.)>
?Preemptive Contact Precautions?
• <If you preemptively place patients at high
risk for CRE on CP, populate this slide. If not,
delete it.>
Patient and Staff Cohorting
• Patient cohorting in dedicated wards or areas
– Dedicated Staff
– Dedicated Equipment
• Healthcare provider and patient education
key!!!
• <Facility-specific instructions for cohorting
here>
26
Removal of Invasive Devices
• 1/3 of all HAIs are device related
• Urinary Catheters
– 25% of patients with Foley > 7days develop CAUTI
– CAUTI risk increases 5% every day of catheter use
• Central Lines
– Central venous catheter
– Pulmonary artery (Swan-Ganz) catheter
– PICCs
• Routine review of device necessity should be carried
out and device should be removed promptly once no
longer clinically indicated <Describe facility-specific
device review protocol(s) here>
27
CRE Screening
• Used to:
– Evaluate prevalence
– Determine if transmission has occurred between
patients
– Identify unrecognized CRE colonization in patients
epidemiologically linked to patients w/known CRE
• Stool, rectal or peri-rectal swabbing is done or
cultures of wounds or urine if they are
indicated
Antimicrobial Stewardship
<Phrase as appropriate to your facility>
An antibiotic stewardship program is in place to
oversee best antimicrobial practices such as:
• Antimicrobials are used for appropriate
indications and duration
• The most narrow-spectrum antimicrobial that
is appropriate for the clinical situation is used
http://www.cdc.gov/getsmart/healthcare/
Additional Consideration: Role of
Environment
Hygiene, hands, patient, and
environment are closely interrelated
because contamination of any one of
these may easily and quickly result in
contamination of the others.
Role of the Environment
"There is no doubt in my mind that
contamination of the environment (surfaces in
patient care areas and medical equipment) play
a major role in the transmission of potential
pathogens. There are well-designed studies
which show patients who occupy the bed of a
patient previously infected with a resistant
pathogen are at greater risk of acquiring that
pathogen.”
~ Michael Phillips, MD, hospital epidemiologist at New York
University, Langone Medical Center
Pyrek K. Communicating the importance of environmental hygiene to healthcare workers. Inf Cntrl
Today. July 14, 2011. http://www.infectioncontroltoday.com/articles/2011/07/communicating-theimportance-of-environmental-hygiene-to-healthcare-workers.aspx
31
CRE Environmental Contamination Study
• 34 known CRE carriers’ environment sampled by contact
plate, environmental swab and environmental swab w/
enrichment. CRE was found on surfaces as follows
–
–
–
–
–
Pillow: 68/204 (33%)
Patient’s crotch: 63/202 (31%)
Patient’s legs 46/198 (23%)
Infusion pump 19/120 (16%)
Personal bedside table 28/204 (14%)
• Overall CRE detected in surroundings of 88% of patients
– Detection rate decreased with increased distance from pt
• Sampling done before and 4h after clothing/sheet
replacement
– 27% pre
– 21% post
Lerner et al. J Clin Microbiol. 2013, 51:177-181
32
Survival of Pathogens on Inanimate Surfaces
Pathogen
Survival
MRSA
7 days – 7 months
VRE
5 days – 4 months
Acinetobacter
3 days -5 months
C. difficile (spores)
5 months
Norovirus
12 – 28 days
E. coli
2 hours – 16 months
Klebsiella spp.
2 hours to > 30months
Kramer A, et al (2006). BMC Infect Dis; 6:130
Environment-to-Hand-to-Patient
Stiefel U, et al. ICHE 2011;32:185-187
40% 45%
Germs can be transferred from surfaces to healthcare worker
hands without direct patient contact!
Environmental Cleaning
• <Fill in facility protocol for environmental cleaning
when patient has a MDRO>
• Monitoring and Feedback
35
Supplemental Measures
Supplemental Measures useful when core
measures do not achieve desired results:
• Active surveillance testing: culturing of patients w/o
an epidemiological link but meet pre-specified
criteria.
• Chlorhexidine bathing
Example CRE “Bundle” -LTAC Bundled
Interventions
•
•
•
•
•
Daily CHG 2% baths for patients
Enhanced environmental cleaning
Surveillance cultures at admission
Serial point prevalence surveys
Training/education of personnel
Munoz-Price et al. Infect Control Hosp Epidemiol 2010; 31:341-347
37
Summary
• CRE rates are increasing
• CRE infections carry high morbidity and mortality
• Treatment options are limited and will remain so for at
least the next 5-10 years
• Control within institutions requires multiple prevention
strategies AND multidisciplinary efforts – EVERYONE
must be informed and active to prevent CRE!
• GOWNS, GLOVES and HAND HYGIENE EVERY TIME!!!
• Antibiotic Stewardship!!!!!!!!!!!!
• More research needed!!!
38
Additional Resources
• CDC’s site on CRE:
http://www.cdc.gov/HAI/organisms/cre/index.html
• http://abcnews.go.com/Health/cre-tops-list-scarysuperbugs/story?id=18666434#.UeW4_xZB7N8
• http://www.cbsnews.com/video/watch/?id=50150
323n superbug cases found in at least 43 states CBS News Video
• Oregon state CRE toolkit:
http://public.health.oregon.gov/DiseasesCondition
s/DiseasesAZ/CRE/Documents/cre_toolkit.pdf