CDC HAN Advisory: Increase In CRE Reports In The United States

 

 

 

Credit CDC HAN

# 6945

 

Regular readers are aware that - while still fairly rare -reports of patients with CRE (Carbapenem-resistant Enterobacteriaceae) colonization or infection are on the rise in hospitals around the world, and across the nation. 

 

Enterobacteriaceae comprise a large family of Gram-negative bacteria that range from harmless strains to pathogenic invaders, and includes such familiar names as Salmonella, Escherichia coli, Klebsiella and Shigella.

 

Carbapenem-resistant Enterobacteriaceae are varieties that have developed resistance to a class of antibiotics called carbapenems, which are often the drug of last resort for treating difficult bacterial infections.

 

Just last Thursday, in MMWR: Denver Hospital Outbreak Of NDM-Producing CRKP, we looked at one hospital’s response to an outbreak of NDM-Producing CRKP in 2012.

 

Other recent blogs on this growing threat include:

 

ECDC: Multidrug Resistant Infections Increasing In Europe

EID: Environmental NDM-1 Detected In Vietnam

MMWR: NDM-1 Transmission In Rhode Island

Netherlands: Large Nosocomial KPC Outbreak

 

Underscoring the importance of getting control over these rising infections, yesterday the CDC published the following HAN Advisory on the increase of CRE in the United States.

 

This is an official CDC HEALTH ADVISORY

Distributed via the CDC Health Alert Network
February 14, 2013, 12:30 ET
CDCHAN-00341-02-14-2013

New Carbapenem-Resistant Enterobacteriaceae Warrant Additional Action by Healthcare Providers

Summary: Carbapenem-resistant Enterobacteriaceae (CRE) are untreatable or difficult-to-treat multidrug-resistant organisms that are emerging in the United States. Because of increased reports of these multidrug-resistant organisms, CDC is alerting clinicians about the need for additional prevention steps regarding CRE. Key points include:

• While still uncommon, reports of unusual forms of CRE (e.g., New Delhi Metallo-β-lactamase and Verona Integron-mediated Metallo-β-lactamase) in the United States are increasing. Of the 37 unusual forms of CRE that have been reported in the United States, the last 15 have been reported since July, 2012.
• This increase highlights the need for U.S. healthcare providers to act aggressively to prevent the emergence and spread of these unusual CRE organisms.
• Current CDC guidance includes key elements of CRE prevention (e.g., use of Contact Precautions) in healthcare settings.
• Because the vast majority of these unusual organisms were isolated from patients who received overnight medical treatment outside of the United States, additional measures described in this HAN advisory are now recommended to be taken when such patients are hospitalized in the United States.

Background

Klebsiella species and Escherichia coli are examples of Enterobacteriaceae, a family of bacteria that normally live in water, soil, and the human gut. CRE are Enterobacteriaceae that have developed high levels of resistance to antibiotics, including last-resort antibiotics called carbapenems. CRE infections most commonly occur among patients who are receiving antibiotics and significant medical treatment for other conditions.

 

Although there are a large number of mechanisms that can lead to carbapenem resistance among Enterobacteriaceae, the production of an enzyme that breaks down broad-spectrum carbapenem antibiotics (carbapenemases) has emerged as an important mechanism in the United States over the last decade. Most carbapenemase-producing CRE in the United States produce a carbapenemase called Klebisella pneumoniae carbapenemase, or KPC, which was first reported in 2001 and has been found in many different types of Gram-negative bacteria.

 

KPC-producing Enterobacteriaceae appear to have spread throughout the United States since 2001 but still remain relatively uncommon in most hospitals. Enterobacteriaceae producing other carbapenemases, such as New Delhi Metallo-β-lactamase (NDM) and the Verona Integron-mediated Metallo-β-lactamase (VIM), have been very uncommon in the United States but are more common in other parts of the world. Many countries may not be actively looking for CRE; therefore, it is unclear which countries have experienced unusual carbapenemases (e.g., NDM, VIM) and it is difficult to know their overall incidence at any given time. The vast majority of CRE producing non-KPC carbapenemases reported to CDC were isolated from patients with a history of an overnight stay in a healthcare facility outside the United States.

Recommendations

CDC continues to recommend that facilities follow the CDC guidance for preventing the spread of CRE in healthcare settings (http://www.cdc.gov/hai/organisms/cre/cre-toolkit/index.html). Facilities should:

• Ensure that the patient is on Contact Precautions.
• Reinforce and evaluate adherence to hand hygiene and Contact Precautions for healthcare personnel who come into contact with the patient (e.g., enter the patient’s room).
• Since clinical cultures will identify only a minority of patients with CRE, screen epidemiologically linked patient contacts for CRE colonization with stool, rectal, or perirectal cultures. At a minimum, this should include persons with whom the CRE patient shared a room but could also include patients who were treated by the same healthcare personnel. A laboratory-based screening protocol is available here: (http://www.cdc.gov/HAI/pdfs/labSettings/Klebsiella_or_Ecoli.pdf).
• Should the patient be transferred to another healthcare facility, ensure that the presence of CRE colonization or infection is communicated to the accepting facility. An example transfer form is available here (http://www.cdc.gov/HAI/toolkits/InterfacilityTransferCommunicationForm11-2010.pdf).
• Dedicate rooms and staff to CRE patients when possible. It is preferred that staff caring for CRE patients do not also care for non-CRE patients.
• Remove temporary medical devices as soon as they are no longer needed.

In addition to that guidance, CDC now also recommends the following:

• When a CRE is identified in a patient (infection or colonization) with a history of an overnight stay in a healthcare facility (within the last 6 months) outside the United States, send the isolate to a reference laboratory for confirmatory susceptibility testing and test to determine the carbapenem resistance mechanism; at a minimum, this should include evaluation for KPC and NDM carbapenemases.
• For patients admitted to healthcare facilities in the United States after recently being hospitalized (within the last 6 months) in countries outside the United States, consider each of  the following:
  • Perform rectal screening cultures to detect CRE colonization.
  • Place patients on Contact Precautions while awaiting the results of these screening cultures.

Further information about the prevention of CRE transmission is available in CDC’s CRE toolkit (http://www.cdc.gov/hai/organisms/cre/cre-toolkit/index.html).

The Centers for Disease Control and Prevention (CDC) protects people's health and safety by preventing and controlling diseases and injuries; enhances health decisions by providing credible information on critical health issues; and promotes healthy living through strong partnerships with local, national, and international organizations.

 

 

The CDC’s Health Alert Network (HAN) is designed to ensure that communities, agencies, health care professionals, and the general public are able to receive timely information on important public health issues.

 

You can sign up for HAN messages, and scores of other CDC and HHS email notifications, by going to the CDC - Quick Subscribe GovDelivery page

 

The problems of growing antibiotic resistance has no better spokesperson than Maryn McKenna on her excellent Superbug Blog, and in her book Superbug: The Fatal Menace of MRSA.

Both highly recommended.

MMWR: Denver Hospital Outbreak Of NDM-Producing CRKP

 

CDC Guidance For Control Of CRE

# 6937

 

Today’s MMWR has the details on an outbreak of NDM-Producing CRKP, or Carbapenem-Resistant Klebsiella pneumoniae, at an acute-care hospital in Denver during first 10 months of 2012. Klebsiella pneumoniae is a Gram negative, rod shaped bacterium commonly found in the flora of the human intestinal tract.

 

Most of the time, it resides harmlessly in the intestines.

 

But when K. pneumoniae moves beyond the intestinal tract – particularly in people with weakened immune systems – it can cause cause severe pneumonia, urinary tract infections (UTI), septicemia, and soft tissue infections.

 

Complicating matters, over the past decade doctors have seen the emergence of antibiotic resistant forms of K. pneumoniae – known as CRKP or  KPC (K. pneumoniae carbapenemase). 

 

Bacteria resistant to the Carbapenem class of antibiotics (a class that includes imipenem, meropenem, doripenem, and ertapenem) – are called carbapenemases –  are of particular concern since Carbapenems are often the drug of last resort for treating difficult bacterial infections.

 

The reference to NDM-Producing is the detection of an emerging enzyme – called NDM or New Delhi metallo-beta-lactamase – that confers resistance to a number of different bacteria. The NDM enzyme was first detected in Sweden in 2008 from a patient with travel history to India.

 

Two and a half years ago The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al. that sounded the alarm on the emergence and growing prevalence of the NDM-1 enzyme on the Indian sub-continent.

 

Of particular concern, this NDM enzyme is carried by a plasmid – a snippet of portable DNA  - that can be easily transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).

 

Since the discovery of NMD-1 5 years ago, scattered variants have begun to emerge; NDM-2, NDM-4, and NDM-5.

 

Up until now, the primary risk for contracting an NMD producing bacterial infection has been receiving medical care in those regions of the globe where these resistant strains have become endemic – notably South Asia.

 

But increasingly, these resistant organisms are making their way around the globe (presumably spread by asymptomatic carriers), and as the following report indicates, how it gets into a medical facility isn’t always known.

 

But once introduced, it can be very difficult to contain.

 

 

Notes from the Field: Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase — Denver, Colorado, 2012

Weekly

February 15, 2013 / 62(06);108-108

On August 16, 2012, the Colorado Department of Public Health and Environment was notified of two patients at an acute-care hospital in Denver with carbapenem-resistant Enterobacteriaceae (CRE), specifically Klebsiella pneumoniae (CRKP), isolated from respiratory specimens during July–August. Both isolates produced New Delhi metallo-beta-lactamase (NDM). A review of microbiology records identified a third patient with NDM-producing CRKP isolated from a respiratory specimen, admitted in May. Active surveillance cultures in September identified an additional five patients colonized with NDM-producing CRKP. An investigation was launched by the hospital and the Colorado Department of Public Health and Environment to guide infection control measures and limit transmission.

 

A case was defined as NDM-producing CRE isolated from clinical or active surveillance cultures collected from a patient while hospitalized during January 1–October 30, 2012. Medical records were reviewed for clinical and epidemiologic characteristics. Relatedness of isolates was evaluated by pulsed-field gel electrophoresis (PFGE).

 

The eight patients were aged 23–75 years and had been hospitalized at one or more of 11 different units in the hospital for a median of 18 days (range: 12–83 days) before CRKP identification. Three were treated for CRKP infection, and five were found to be asymptomatically colonized; none died. Initial isolates were resistant to all antimicrobials except tigecycline, to which all were susceptible. Colistin minimum inhibitory concentrations for six isolates were low (≤2 µg/mL), suggesting this agent might be a treatment option. All isolates were highly related by PFGE. Epidemiologic tracing to determine temporal overlap of patients on units in the hospital indicated multiple transmission events had occurred, and three units were likely transmission sites. Acquisition of NDM-producing CRE by some patients was not explained by direct overlap and suggested that undetected, asymptomatically colonized patients were involved in some transmission routes. How NDM-producing CRE was introduced to the facility is unclear.

 

NDM, a carbapenemase enzyme first described in 2009 in a patient who had received medical care in India (1), has since been detected and reported worldwide (2). In the United States, before this outbreak, only 16 isolates in clusters with two or fewer cases had been identified since 2009; 14 isolates were from patients who had received medical care in endemic (South Asian) regions. The cases described here represent the largest U.S. outbreak of NDM-producing CRE to date, highlighting the risk for spread of these organisms among persons receiving medical care inside the United States. Evidence that undetected, asymptomatically colonized patients likely contributed to the size of the outbreak highlights the importance of timely active surveillance cultures when CRE is identified to direct infection control measures and limit further transmission (3).

Reported by

Larissa Pisney, MD, Michelle Barron MD, Div of Infectious Diseases, Univ of Colorado; Sarah Jackson Janelle, MPH, Wendy Bamberg, MD, Colorado Dept of Public Health and Environment. Duncan MacCannell, PhD, Antimicrobial Resistance and Characterization Laboratory; Alexander Kallen, MD, Carolyn Gould, MD, Brandi Limbago, PhD, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases; Erin Epson, MD, Joyanna Wendt, MD, EIS officers, CDC. Corresponding contributor: Erin Epson, erin.epson@state.co.us, 303-692-2745.

 

 

While some of the warnings issued over the past couple of years regarding the growth and spread of antibiotic resistant organisms may have seemed a bit hyperbolic to the general public, I firmly believe that modern medicine will face no greater challenge over the next couple of decades.

 

Few, if any, new classes of antibiotics are in the pipeline, and with each passing day bacteria get better at evading our dwindling antibiotic arsenal.

 

The rise of antibiotic resistance - including these emerging NDM enzymes - has long been linked to the overuse and misuse of antibiotics. A practice that is still widespread in many parts of the world, but is particularly rampant on the Indian sub-continent.

 

Citing a lack of doctors and low family incomes, the Indian government (see India: Still Looking For A Policy On Antibiotics) has been slow to stop the sale of antibiotics to the public without a doctor’s prescription.

 

For more on the importance of proper antibiotic stewardship, you may wish to revisit these earlier blogs.

 

Chan: World Faces A `Post-Antibiotic Era’

Get Smart About Antibiotics Week

IDSA: Educational Guidelines Lower Antibiotic Use

 

And for a far more complete discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA.

Superbug (MRSA) Book

 

Meanwhile, Maryn’s SUPERBUG Blog, continues to provide the best day-to-day coverage of these issues.