1. Carbapenem-resistant Enterobacteriacea (ent-ə-rō-ˌbak-ˌtir-ē-ˈā-sē-ˌā) July 2013

2. Outline
Background
Epidemiology
Control

3. 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
Carbapenems are a group of antibiotics that are usually reserved to treat serious infections, particularly when these infections are caused by germs that are highly resistant to antibiotics. Sometimes carbapenems are considered antibiotics of last resort for some infections. Some Enterobacteriaceae can no longer be treated with carbapenems because they have developed resistance to these antibiotics (i.e., CRE); resistance makes the antibiotics ineffective in killing the resistant germ. Resistance to carbapenems can be due to a few different mechanisms. One of the more common ways that Enterobacteriaceae become resistant to carbapenems is due to production of Klebsiella pneumoniae carbapenemase (KPC). KPC is an enzyme that is produced by some CRE that was first identified in the United States around KPC breaks down carbapenems making them ineffective.  Other enzymes, in addition to KPC, can breakdown carbapenems and lead to the development of CRE,

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. First case in U.S. showed up in NC in 2001 !
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 !

7. 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.

8. Carbapenem resistance in K. pneumoniae HAIs -NHSN
Time
CLABSI
CAUTI
VAP
SSI
11% 9% 4%
12.5%
12.8%
11.2%
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
Sievert et al. Infect Control Hosp Epidemiol 2013;34(1):1-14
Hidron, A et al Infect Control Hospital Epidemiol. 2008;29:996

9. 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.

10. 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.

11. 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.
Healthy people usually don’t get CRE infections. CRE primarily affect patients in acute and long-term healthcare settings, who are being treated for another condition. CRE are more likely to affect those patients who have compromised immune systems or have invasive devices like tubes going into their body. Use of certain types of antibiotics might also make it more likely for patients to get CRE.
Patel et al. ICHE 2008; 29:
Schwaber et al. Antimicrob Agents Cehmother 2008; 52:
Hussein et al. ICHE 2009; 30:666-71

12. 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):

13. 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
*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:

14. This is an example of how a patient, Jan, develops a CRE infection
This is an example of how a patient, Jan, develops a CRE infection. Jan is admitted to the local acute care hospital where she is diagnosed with a stroke. She improves but needs ongoing intensive care at a long-term acute care hospital, to which she’s transferred. Jan gets CRE from the hands of a nurse who did not perform adequate hand hygiene and who picked the germs up on his hands from other patients in the LTACH. Jan’s temperature spikes and her doctor orders antibiotics, without fully culturing her before starting them. Jan then becomes unstable and has to be transferred back to the acute-care hospital, taking CRE with her, unknown to her new healthcare team there. CRE spreads to the hospital… Due to the movement of patients throughout the healthcare system, if CRE are a problem in one facility, then typically they are a problem in other facilities in the region as well.

15. 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.

16. 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.

17. CDC Toolkit – An Important Resource

18. CRE Control: No Magic Bullet but some Core Prevention Strategies from the CDC
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

19. 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.)>
Laboratories should have protocols in place that facilitate the rapid notification of appropriate clinical and infection prevention staff whenever CRE are identified from clinical specimens to ensure timely implementation of control measures. This is true for both facilities with on-site laboratories and those sending cultures off-site and is applicable to acute and long–term care settings.

20. Surveillance <Insert facility CRE surveillance plan/protocol(s)>
Be aware of whether or not CRE (at least E.coli and Klebsiella species) have ever been cultured from patients admitted to your facility. (upon transfer in). Be aware of positive cultures for CRE after admission. (Immediate lab notification of IP and nursing unit.)
If CRE have been/are present, facilities should also determine:
If there is evidence of intra-facility transmission
Which wards/units are most affected
Consider including questions about multi-drug resistant organisms, including CREs, on all transfer forms between facilities and between intra-facility units/departments.

21. 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!

22. 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.

23. Contact Precautions
<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>
<Place your CP sign here>
Contact Precautions (CP) are still indicated for residents infected or colonized with CRE; however, these might be modified to fit the inherent differences between acute and long-term care facilities. Contact Precautions should be used for residents with CRE who are at higher risk for transmission, including patients who are totally dependent upon HCP for their activities of daily living, are ventilator-dependent, are incontinent of stool, or have wounds with drainage that is difficult to control. For other residents who are able to perform hand hygiene, are continent of stool, are less dependent on staff for their activities of daily living, and are without draining wounds, the requirement for Contact Precautions might be relaxed. However, in these situations Standard Precautions should still be observed, including the use of gloves and/or gowns when contact with colonized/infected sites or body fluids is possible.

24. 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.)>

25. ?Preemptive Contact Precautions?
<If you preemptively place patients at high risk for CRE on CP, populate this slide. If not, delete it.>
Preemptive Contact Precautions, often in conjunction with surveillance cultures, might be used on patients transferred from high-risk settings (see supplemental interventions in the CDC CRE toolkit) pending results of screening cultures. Examples include transferred patients from hospitals in countries or areas in the United States where CRE are common or patients transferred from facilities known to have outbreaks or clusters of CRE colonized or infected patients. In long-term care settings, Contact Precautions are still indicated for residents infected or colonized with CRE; however, these might be modified to fit the inherent differences between acute and long-term care facilities. Contact Precautions should be used for residents with CRE who are at higher risk for transmission, including patients who are totally dependent upon HCP for their activities of daily living, are ventilator-dependent, are incontinent of stool, or have wounds with drainage that is difficult to control. For other residents who are able to perform hand hygiene, are continent of stool, are less dependent on staff for their activities of daily living, and are without draining wounds, the requirement for Contact Precautions might be relaxed. However, in these situations Standard Precautions should still be observed, including the use of gloves and/or gowns when contact with colonized/infected sites or body fluids is possible.

26. 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>
When available, patients colonized or infected with CRE should be housed in single patient rooms and if not available these patients should be cohorted together. In addition, consideration should be given to cohorting patients with CRE in specific areas (e.g., units or wards), even if in single patient rooms, and to using dedicated staff to care for them. This recommendation applies to both acute and long-term care settings. Preference for single rooms should be given to patients at highest risk for transmission such as patients with incontinence, medical devices, or wounds with uncontrolled drainage.

27. 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>
Use of devices (e.g., central venous catheters, endotracheal tubes, urinary catheters) puts patients at risk for device–associated infections and minimizing device use is an important part of the effort to decrease the incidence of these infections. Additionally, device use has been associated with carbapenem resistance among Enterobacteriaceae. Therefore, minimizing device use in all healthcare settings should be part of the effort to decrease the prevalence of all MDROs including CRE. In acute and long-term care settings, device use should be reviewed regularly to ensure they are still required and devices should be discontinued promptly when no longer needed. For more information on preventing device-associated infection including appropriate use of devices please see CDC’s Guidelines for the Prevention of Intravascular Catheter-Related Infections and Guideline for Prevention of Catheter-associated Urinary Tract Infections, 2009.

28. 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
Screening is used to identify unrecognized CRE colonization among epidemiologically linked contacts of known CRE colonized or infected patients as clinical cultures will usually identify only a fraction of all patients with CRE. Generally, this screening has involved stool, rectal, or peri-rectal cultures and sometimes cultures of wounds or urine (if a urinary catheter is present). A laboratory protocol for evaluating rectal or peri-rectal swabs for CRE  [PDF KB] is available however, it is important to note that this procedure has only been validated for E. coli and Klebsiella spp. CRE screening of epidemiologically linked patients is a primary prevention strategy for all healthcare facilities; however, it is particularly important for healthcare facilities with CRE outbreaks or facilities that do not or only rarely admit patients with CRE infection or colonization. This intervention is applicable to both acute and long-term care settings.

29. 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
For more information on antimicrobial stewardship in healthcare settings please seehttp://

30. 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.

31. 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,

32. 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
Pillow: 68 out of 204 cultures or 33%
Patient’s crotch: 63 out of 202 cultures (31%)
Patient’s legs 46 out of 198 cultures (23%)
Infusion pump 19 out of 120 cultures or 16%
Personal bedside table 28/204 (14%)
Lerner et al. J Clin Microbiol. 2013, 51:

33. Survival of Pathogens on Inanimate Surfaces
MRSA
7 days – 7 months
VRE
5 days – 4 months
Acinetobacter
3 days -5 months
difficile (spores)
5 months
Norovirus
12 – 28 days
E. coli
2 hours – 16 months
Klebsiella spp.
2 hours to > 30months
We know that colonized or infected patients broadly contaminate their immediate environment. Once pathogens are on surfaces, they can live for quite some time. In looking a the numerous studies published in the literature, many of these pathogens can live several months on dry surfaces. Healthcare workers as well as patients and visitors can easily contaminate their hands from the environment and spread to others.
Kramer A, et al (2006). BMC Infect Dis; 6:130

34. Environment-to-Hand-to-Patient
Stiefel U, et al. ICHE 2011;32:
40%
45%
Healthcare workers can pick up pathogens from hospital surfaces and carry them to the patient. This study showed that there was no statistical difference between the level of hand contamination from contact with a patient and contact with the environment. That’s one big reason why healthcare workers need to decontaminate their hands before and after entering the patient’s room, whether they touched the patient or not.
Germs can be transferred from surfaces to healthcare worker hands without direct patient contact!

35. Environmental Cleaning
<Fill in facility protocol for environmental cleaning when patient has a MDRO>
Monitoring and Feedback
Good, thorough environmental cleaning is and absolute MUST to prevent spread of infection! Rooms can look clean but be harboring many harmful germs.

36. 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
If done, surveillance testing could be focused on patients admitted to certain high-risk settings (e.g., ICUs, long-term acute care) or could target specific patients (i.e., patients with risk factors, patients admitted from high-risk settings like long-term acute care or transferred from areas with high CRE prevalence). This testing is generally done at admission but can also be done periodically during admission (e.g., weekly). Patients identified as positive by this surveillance testing should be treated as colonized (i.e., placed on Contact Precautions, etc.). In some situations
(e.g., patients admitted from high-risk settings) patients might be placed in preemptive Contact Precautions until surveillance testing is found to be negative.
As with screening of epidemiologically linked CRE contacts, the use of active surveillance testing to control CRE is applicable to both acute and long-term care settings.

37. 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:

38. 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!!!

39. Additional Resources
CDC’s site on CRE:
superbug cases found in at least 43 states - CBS News Video
Oregon state CRE toolkit: