Carbapenem-resistant Enterobacteriacae

What are CRE?

Carbapenem-resistant Enterobacteriacae (CRE) [also known as carbapenemase-producing Enterobacteriacae (CPE)] is the collective name for a family of microorganisms that have high levels of resistance to antibiotics. Two of the most common bacteria in the Enterobacteriacae family that can develop resistance to carbapenem antibiotics family include Escherichia coli (E. coli), and species of Klebsiella. Others include species of Serratia, Enterobacter, Salmonella and Citrobacter.

CRE are sometimes referred to by the names of the enzymes – the carbapenemases – that break down carbapenem antibiotics such as imipenem, ertapenem, meropenem and doripenem. Three well-known CRE include KPC (Klebsiella pneumoniae carbapenemase), NDM (New Delhi Metallo-beta-lactamase) and OXA-48. CRE are resistant to many antibiotics, with some being resistant to all or almost all antibiotics. As a result, infections are very difficult to treat; CRE bloodstream infections can kill 1 in 2 patients.

The Centers for Disease Control and Prevention (CDC) tracks infections caused by bacteria producing specific enzymes including NDM-1, OXA-48 and KPC as well as VIM (Verona Integron-Mediated Metallo-β-lactamase) and IMP (Imipenemase Metallo-beta-lactamase). As of December 2017, KPC CRE infections have been reported in 50 states, and NDM-1 and OXA-48 CRE infections in over 25 states. Around a dozen states have reported VIM and IMP infections.1

Why are CRE a concern?

CRE are a concern globally for a number of reasons.2

  • Some CRE are resistant to multiple classes of antibiotics, not just carbapenemases.
  • With some carbapenemases such as KPC, the genes that code for resistance are on a highly mobile genetic element which can be transmitted from one Enterobacteriaceae to another, facilitating the transmission of resistance from one species to another.
  • Mortality rates from some CRE infections are as high as 50%.
  • CRE cause infections in both community and healthcare settings.

Who is at risk of CRE infections?

CRE infections most commonly affect already sick patients in acute and long-term healthcare settings who are typically being treated for other conditions. Risk factors also include having a compromised immune system, having invasive devices such as catheters or mechanical ventilators going into the body, or use of certain types of antibiotics (such as carbapenems, cephalosporins, fluoroquinolones, and vancomycin).3 Several outbreaks of CRE have also been reported amongst patients undergoing a life-saving medical procedure called ERCP (endoscopic retrograde cholangiopancreatography) in which a duodenoscope is inserted through the mouth and intestine to where the bile duct attaches.4 Some CRE have originated in overseas countries such as India (NDM) so receipt of healthcare in countries where CRE is endemic may also be a risk factor.

Patients may also be colonized with CRE, meaning that the organism can found in a clinical culture but not be causing an infection. In such cases, infections may result if the colonized strain access sterile body sites such as the bloodstream, lungs and bladder. Signs and symptoms may then include those commonly associated with those body sites but also general fever and chills.

How are CRE spread?

CRE spread primarily in healthcare settings and often through person to person transmission from the contaminated hands of healthcare personnel or contaminated equipment to patients. Transmission from the environment directly to patients is not well-understood and requires more research. However, studies are showing that CRE can exist on surfaces and equipment in the environment and could contaminate healthcare personnel hands and then be transmitted to patients. One study has found CRE on a variety of surfaces in the rooms of patients infected with KPC, with the bed linen and area around the bed being the most contaminated.5 In recent years, multiple studies have shown that hospital sink drains and particularly those in the ICU can be reservoirs.6 Water from faucets hitting the contaminated sink drain can splash to surrounding surfaces containing IV bags, medications and patient equipment. Some studies have also demonstrated that contaminated sinks were the source of CRE outbreaks.7,8

Preventing the Spread of CRE

The CDC provides useful guidance and resources for controlling and preventing the spread of CRE in healthcare facilities.9

Surveillance and laboratory notification: Three carbapenemase-producing CRE (CP-CRE) are included on the CDC’s National Notifiable Infectious Diseases Surveillance System (NNDSS) — CP-CRE Enterobacter spp, CP-CRE Escherichia coli and CP-CRE Klebsiella spp. Facilities should have samples tested at their laboratories if testing is available, or at outside laboratories with this capability. Results should be reported to state and local health authorities who will then notify the CDC. Clinical and infection prevention staff at f CRE acilities should also be notified within 4-6 hours when positive CRE cultures are identified.

Implement contact precautions: All identified CRE infected or colonized patients should be placed on contact precautions which include hand hygiene before putting on gown and gloves, putting on PPE (gown and gloves) before entering the patient room, and removing PPE and performing hand hygiene before leaving the room.

Minimize the use of devices: Indwelling devices such as catheters and endotracheal tubes are risk factors for CRE infection should be reviewed regularly and removed immediately when no longer required.

Inter-facility communication: Notify receiving facilities of a patient’s status and include any plans for the patient’s indwelling devices and information on duration and type of antimicrobial therapy being administered.

Educate personnel: Healthcare personnel and EVS should be educated on CRE, particularly on the importance of contact precautions, hand hygiene and environmental disinfection.

Antimicrobial stewardship: Use the narrowest spectrum antibiotic for the indication and for the appropriate duration.

Environmental cleaning and disinfection: Perform daily cleaning of patient rooms, especially focusing on the areas around the patient bed such as bed rails, bedside and over-bed tables and IV poles. Because sink drains have been identified as potential CRE sources, surfaces around sinks should be cleaned and disinfected regularly, and patient supplies and medical equipment not stored near or on splash zones around sinks. Follow product label directions for use and ensure that surfaces remain wet for the full contact time listed on the product label.

Clorox Healthcare products with EPA-approved claims against CRE

A number of Clorox Healthcare disinfectants have EPA-approved claims against some common CRE.

Product            EPA Reg. No.     Klebsiella
pneumoniae

(KPC)
Klebsiella
pneumoniae

(NDM-1)
Escherichia
coli
(carbapenem-
resistant)
Escherichia coli
(NDM-1)
Enterobacter cloacae
(NDM-1)
Clorox Healthcare® Bleach Germicidal Wipes 67619-12 30 sec 30 sec   30 sec  
Clorox Healthcare® Bleach Germicidal Cleaner Spray 56392-7 1 min 1 min   1 min 1 min
Clorox Healthcare® Fuzion® Disinfectant Cleaner 67619-30 1 min 1 min     1 min
Clorox Healthcare® Hydrogen Peroxide Cleaner Disinfectant 67619-24 30 sec 30 sec   30 sec  
Clorox Healthcare® Hydrogen Peroxide Cleaner Disinfectant Wipes 67619-25 30 sec 30 sec   30 sec  
Clorox Healthcare® VersaSure® Cleaner Disinfectant Wipes 67619-37 2 min   2 min    
Clorox® Total 360® Disinfecting Cleaner 67619-38   2 min      
CloroxPro™ Clorox® Clean-Up® Disinfectant Cleaner with Bleach (Spray) 67619-17 30 sec        
CloroxPro™ Clorox® Disinfecting Spray 67619-21 3 min        
CloroxPro™ Clorox® Germicidal Bleach 67619-32     5 min 5 min 5 min

References

1. Centers for Disease Control and Prevention. Tracking CRE. https://www.cdc.gov/hai/organisms/cre/trackingcre.html
2. Centers for Disease Control and Prevention. Carbapenem-resistant Enterobacteriaceae (CRE) Infection: Clinician FAQs. https://www.cdc.gov/hai/organisms/cre/cre-clinicianfaq.html
3. Bhargava A et al. Risk Factors for Colonization due to Carbapenem-Resistant Enterobacteriaceae among Patients Exposed to Long-Term Acute Care and Acute Care Facilities. Infection Control and Hospital Epidemiology, 2014; 35(4): 398-405.
4. CDC Statement: Los Angeles County/UCLA investigation of CRE transmission and duodenoscopes. July 10, 2015. https://www.cdc.gov/hai/outbreaks/cdcstatement-la-cre.html
5. Lerner A et al. Environmental Contamination by Carbapenem-Resistant Enterobacteriaceae. J Clin Microbiol. 2013; 51(1): 177–181.
6. Kizny A et al. The Hospital Water Environment as a Reservoir for Carbapenem-Resistant Organisms Causing Hospital-Acquired Infections—A Systematic Review of the Literature. Clinical Infectious Diseases. 2018; 64:1435-1444.
7. De Geyter A et al. The sink as a potential source of transmission of carbapenemase-producing Enterobacteriaceae in the intensive care unit. Antimicrobial Resistance and Infection Control, 2017; 6:24-29.
8. Regev-Yochay G et al. Sink traps as the source of transmission of OXA-48–producing Serratia marcescens in an intensive care unit. Infection Control & Hospital Epidemiology 2018; 39:1307–1315.
9. Centers for Disease Control and prevention. Facility Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE) November 2015 Update – CRE Toolkit. https://www.cdc.gov/hai/pdfs/cre/CRE-guidance-508.pdf

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