CARBAPENEM-RESISTANT ENTEROBACTERIACEAE (CRE)
The Latest in Antibiotic Resistance
The full name might be unpronounceable, but CRE is too scary to ignore. When we think of the term "superhero," we often envision a character that possesses superhuman strength, extraordinary talents, and the overwhelming dedication to protecting the public from harm. However, now we shift gears to think about the emergence of the Superbug. While this new breed of microorganisms possesses similar qualities to superheroes, they are, in fact, the arch nemesis.
In 1928, penicillin was first discovered by Alexander Fleming. The discovery marked a momentous occasion in medicine. Through the years, newer and more potent antibiotics have been developed. While countless lives have been saved, we are now seeing an alarming emergence of antibiotic resistance.
The Age of Resistance
According to Lautenbach and Perencevich (2014), “Approximately 10% of hospitalizations are complicated by a healthcare-associated infection, and up to 75% of these are due to organisms resistant to first-line antimicrobial therapy” (p.333). Morbidity and mortality have notably increased. These statistics increase annual healthcare costs by $20 billion. Lost productivity can cost society another $35 billion a year (CDC, 2013; Lautenbach & Perencevich, 2014; Orsini et al., 2012).
In 2013, the CDC (Centers for Disease Control and Prevention) published a report outlining the threat of antibiotic resistance, and how the medical community can fight back. They prioritized bacteria into three categories according to their level of risk; urgent, serious, and concerning.
- The first category, "Urgent," has been defined by the CDC (2013) as: “High-consequence antibiotic-resistant threats because of significant risks identified across several criteria. These threats may not be currently widespread but have the potential to become so and require urgent public health attention to identify infections and to limit transmission” (pg. 21). These include: Clostridium difficile (C. difficile), Carbapenem-resistant Enterobacteriaceae (CRE), and Drug-resistant Neisseria gonorrhoeae.
- The second category is labeled "Serious" and defined by the CDC (2013) as: “These are significant antibiotic-resistant threats. For varying reasons (e.g., low or declining domestic incidence or reasonable availability of therapeutic agents), they are not considered urgent, but these threats will worsen and may become urgent without ongoing public health monitoring and prevention activities.” (pg 21) These threats include: Multidrug-resistant Acinetobacter, Drug-resistant Campylobacter, Fluconazole-resistant Candida (a fungus), Extended spectrum B-lactamase producing Enterobacteriaceae (ESBLs), Vancomycin-resistant Enterococcus (VRE), Multidrug-resistant Pseudomonas aeruginosa, Drug-resistant Non-typhoidal Salmonella, Drug-resistant Salmonella Typhi, Drug-resistant Shigella, Methicillin-resistant Staphylococcus Aureus (MRSA), Drug-resistant Streptococcus pneumoniae and Drug-resistant tuberculosis.
- The final category, "Concerning," is defined by the CDC (2013) as: “These are bacteria for which the threat of antibiotic resistance is low, and/or there are multiple therapeutic options for resistant infections. These bacterial pathogens cause severe illness. Threats in this category require monitoring and in some cases rapid incident or outbreak response." (pg. 21) Examples of this category include: Vancomycin-resistant Staphylococcus aureus (VRSA), Erythromycin-resistant Group A Streptococcus, and Clindamycin-resistant Group B Streptococcus.
Fight the Resistance
The CDC identifies four core actions to precent antibiotic resistance.
- Preventing Infections and Preventing the Spread of Resistance: Avoiding infection all together would eliminate the need for antibiotics and the chance of developing resistance. Ways to prevent drug-resistant infections include proper hand hygiene, judicious use of antibiotics, safe food preparation and immunizations.
- Tracking Patterns of Resistance: The CDC gathers data, and it is used by experts to help understand patterns and develop strategies to prevent the spread of resistant bacteria.
- Antibiotic Stewardship: Up to half of the time, antibiotics are prescribed when not needed or are used incorrectly. Creating protocols and sticking to them is paramount.
- Developing New Antibiotics and Diagnostic Tests: As bacteria continue to evolve, new antibiotics will be needed to combat their presence as well as new methods to track the resistance (CDC, 2013).
Carbapenem-Resistant Enterobacteriaceae (CRE)
CRE has become familiar to the general public in recent months. The first reported case in the United States occurred in 2001. By 2012, CRE had spread to over 200 hospitals in 42 states (Deen & Debbie, 2014). In 2013, a report published by the CDC said that approximately 9,300 health-care associated Enterobacteriaceae infections occur and nearly 600 deaths result in the U.S. yearly from these infections. CRE has been publicized with names such as, “deadly superbug,” “nightmare bacteria,” and “dangerous bacteria” (Davis & Cunha 2014; Deen & Debbie, 2014).
Why is CRE So Dangerous?
Two common genera of CRE include Klebsiella and Escherichia Coli. These bacteria, which are found in the intestines, do not usually cause disease. In certain cases, they can move from the digestive system causing urinary tract infections, bloodstream infections, wound infections and pneumonia (Deen & Debbie, 2014).
Muscarella (2014) described what sets CRE apart. “First, these bacteria are resistant to multiple classes of antimicrobial drugs. In fact, some strains of CRE are pan-resistant (i.e. resistant to all antibiotics). Second, these resistant bacteria can share mobile pieces of genetic material, conferring their antibiotic resistance to other once-susceptible bacteria that are physically nearby and of either the same or a different species or family of bacteria” (pg. 461). Patients that develop infections associated with this bacteria have significantly worse clinical outcomes. The mortality rate once CRE reaches the bloodstream can be as high as 50% (Muscarella, 2014).
CRE is transmitted by direct contact, either person to person or contact with contaminated surfaces. Studies have found CRE on staff stethoscopes and name badges, as well as sinks in the intensive care unit. Post-acute care and long-term care facilities have been found to have a large number of patients colonized with CRE, as well as contaminated surfaces (Deen & Debbie, 2014).
Medical instruments such as the duodenoscope pose an especially high risk of transmission due to their complex design. Duodenoscopes are flexible, lighted tubes which are passed through the mouth to the duodenum. They contain a hollow channel in the middle, which allows injection of contrast material and insertion of other instruments. The difference is, these scopes have a moveable “elevator” mechanism at the tip. While this allows the operator more flexibility with the angle of the scope, this poses a problem when they are cleaned due to areas that are extremely difficult to reach. The FDA continues to monitor the association between the device use and multi-drug resistant infections. They recommend following the reprocessing guidelines and practices established by infection control and endoscopy experts (U.S. Food and Drug Administration, 2015).
Several factors have been identified that increase a patient’s risk of becoming infected with CRE. These include; advanced age, previous exposure to broad-spectrum antibiotics, being treated in acute and long-term care settings, having invasive devices such as a urinary catheter or central venous line, treatment with mechanical ventilation, being immuno-suppressed (i.e. transplant recipients), and those undergoing endoscopic procedures such as Endoscopic Retrograde Cholangiopancreatography, otherwise known as ERCP (Deen & Debbie, 2014; Muscarella, 2014).
Treating CRE is challenging due to the limited number of effective antibiotics available. Treatment typically includes using a combination of drugs such as aminoglycosides, polymyxins (such as colistin), tigecycline, fosfomycin, and temocillin. Using these potent medications does not come without paying a price. Many have toxic side effects which further complicate the patient’s hospital course (Davis & Cunha 2014; Deen & Debbie, 2014; Muscarella, 2014).
The side effects vary in severity. With colistin, neurotoxicity and nephrotoxicity have occured. The efficacy of tigecycline has been in question, and clinical trials have shown higher mortality rates in those patients treated with this drug as compared with others available. Most experts discourage the use of the drug as monotherapy. Nausea is the most common side effect with tigecycline but other issues such as pancreatitis, and extreme alkaline phosphatase elevations have been reported. Aminoglycosides carry their risk as well, such as ototoxicity and nephrotoxicity (Perez & Duin, 2013).
In February 2015, the U.S. Food and Drug Administration issued a safety warning regarding the intricate design of duodenoscopes and the challenges faced when attempting to clean and disinfect them. The FDA pointed out that scope design flaws could be to blame. A number of lawsuits have already been filed against Olympus America, with the possibility of more to come.
With the growing problem of antibiotic resistance and fewer antibiotics to treat these “superbug” infections, healthcare practitioners need to be more vigilant in preventing the spread of resistant organisms. The current CDC recommendations of good hand hygiene, implementing contact precautions, providing education, antibiotic stewardship, staff and patient cohorting and CRE screening only work if each and every person utilizes them.