Vancomycin-Resistant Enterococci

• Enterococci (genus Enterococcus) are bacteria that commonly live in the bowel and are usually resistant to many antibiotics. VRE are enterococci that have become resistant to the antibiotic vancomycin.
• There are only a few antibiotics that are able to treat VRE infections. However, newer antibiotics are being developed.
• People can be colonized with VRE, meaning that the bacteria are living harmlessly in the body.
• VRE causes infection when it invades the bloodstream or spreads locally. It can also be introduced directly into a wound.
• Infection is more likely in people with chronic diseases like diabetes or patients who have recently received antibiotics. It is also more common in patients with indwelling devices like intravenous lines or urinary catheters and those with compromised immune systems.
• VRE can cause many types of infections (for example, bloodstream infection [sepsis], urinary infection, abscesses, wound infections, pneumonia, heart infections [endocarditis], or meningitis).
• To avoid spreading VRE from person to person, it is important to wash or decontaminate hands frequently, including before and after touching the patient or his/her environment. In the hospital, staff will also wear gowns and gloves when caring for a person with VRE.
• The risk of VRE infection can be reduced by minimizing the use of indwelling devices such as intravenous lines and urinary catheters. The risk is also reduced by eliminating inappropriate use of antibiotics.

Enterococci are a group of gram-positive, round-shaped bacteria that commonly live in the gut, although they can cause infection anywhere in the body. They are resistant to several antibiotics, but in the past, physicians could rely on the drug vancomycin to effectively treat enterococcal infections. In recent decades, however, some enterococci have become resistant to vancomycin. The two main species that cause problems are vancomycin-resistant Enterococcus faecium and vancomycin-resistant Enterococcus faecalis. E. faecium is the most common species of VRE. These bacteria are not the same genus as other common fecal bacteria such as E. coli.

Vancomycin resistance is acquired when a sensitive Enterococcus acquires a special piece of DNA called a plasmid that permits the bacteria to become resistant to vancomycin. The new strains are called vancomycin-resistant enterococci (VRE). One concern is that VRE strains appear able to transfer vancomycin resistance to unrelated bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) and these strains are renamed VRSA. In addition, VRE organisms, like MRSA, are usually resistant to more than one antibiotic.

VRE can be spread from person to person and are an increasing problem in hospitals and chronic care facilities. Approximately 30% of all enterococcal infections are now caused by vancomycin-resistant strains (VRE).

VRE can exist in the body without causing infection, in which case a patient is said to be colonized with VRE. Colonization usually occurs in the bowel. If the number of VRE bacteria increases, they can invade the bloodstream or spread locally to cause an abdominal abscess or urinary tract infection. Once in the bloodstream, VRE can cause meningitis, pneumonia, or infection of a heart valve (endocarditis). VRE may also be introduced directly into an open sore or wound, causing a wound infection. The bacteria produce several substances, including proteases that help them break down the normal barriers between the gut tissue and the bloodstream. The vancomycin resistance in the bacteria are caused by a plasmid, a fragment of genetic material that allows the bacteria to be resistant to vancomycin.

VRE are contagious from person to person. However, if a patient takes antibiotics, VRE organisms may develop in the individual (usually in the gastrointestinal tract or on other mucous membranes) and then invade the bloodstream or other areas. These individuals can then be contagious to other people.

VRE can be transmitted from person to person, especially in a hospital or chronic care facility. Microscopic amounts of fecal material from an infected or colonized patient can contaminate the hospital environment and be spread on the hands of health care personnel or by contamination of surfaces such as bedding or clothing. Patients who have VRE may inadvertently contaminate their beds and bathrooms. If the environment is not adequately cleaned, the next patient (or visitor) in the room may be at risk. VRE infections are not spread by coughing or sneezing.

The healthy bowel harbors more than 400 different species of bacteria which compete with each other and help keep any one organism from overgrowing. However, if a patient takes antibiotics, some bacterial species are killed off and the balance among the bacteria is disrupted. In this case, a single species like VRE may increase to the point at which it can invade the bloodstream or cause a local infection. Thus, prior use of antibiotics, especially vancomycin, is a risk factor for infection with VRE. Other risk factors include having a compromised immune system, cancer, a chronic disease like diabetes, or kidney failure. Infection is also more likely if there is a small break in the mucosal membrane (lining) of the bowel or in patients undergoing a gastrointestinal surgery or procedure. Indwelling devices, such as urinary catheters or intravenous lines, increase the risk of infection because they disrupt the normal mucosal or skin barriers and provide a type of artificial reef on which the organisms can grow. If a person is colonized or is hospitalized, their risk for infection with VRE increases.

The incubation period for VRE is not well documented, especially in those patients who develop VRE from taking antibiotics and because some individuals may be carriers of VRE and become infected after some problem that decreases their immune responses or damages their mucus membranes. Estimates of the incubation period vary from days to weeks or even longer, and the contagious period is estimated to be as long as VRE are shed from the patient.

The symptoms of VRE infection vary according to the site of infection. If VRE has invaded the bloodstream, the patient will have fever, a fast heart rate, and feel very sick. This syndrome is called sepsis. In severe cases, the blood pressure may fall, causing shock, although this is less common with VRE than with some other bacteria. Patients with urinary infections (UTI) may experience burning or pain with urination, back pain, difficulty urinating, frequent urination, or fever. Meningitis is uncommon and causes headache, stiff neck, confusion, and/or fever. Infection of a heart valve (endocarditis) causes prolonged sepsis and may cause the valve to leak or fail. Endocarditis is more common if the patient already has a damaged heart valve or an artificial valve. Infected wounds are inflamed, with red and warm skin, soreness, swelling, and contain pus or have pus drainage. Pneumonia causes fever, difficulty breathing, and cough.

Although some VRE infections may be treated by pediatricians and/or primary care physicians, more serious infections may be diagnosed and treated in consultation with emergency-medicine specialists, infectious-disease specialists, internal-medicine specialists, critical care specialists, and in some cases, surgeons. Ancillary personnel who may help manage VRE-infected patients may include hospital infection-control workers and pharmacists.

Diagnosis requires culturing the organism. VRE is easily grown on culture plates in a laboratory. Definitive diagnosis requires that the organisms show resistance to vancomycin; usually sensitivities to additional antibiotics are determined at the same time. To get material to culture, a sample of the infected tissue is taken. For a wound infection, a swab is usually rubbed over the surface to get infected material. Blood is drawn and cultured to detect sepsis or endocarditis. Urine or sputum samples are taken to identify urinary tract infections or pneumonia. If VRE is cultured from blood or spinal fluid, it almost invariably indicates infection. However, if VRE is cultured from sputum, urine, or a wound, it could indicate either colonization or infection. The physician will ask the patient questions and perform a physical exam to help determine if any signs or symptoms of infection of these areas are present. Imaging studies such as X-rays or CT scans may be used to detect pneumonia or abscesses.

VRE are resistant to a wide array of antibiotics. Fortunately, newer antibiotics have been developed to bridge this gap, but sometimes they must be used in combination with other antibiotics. Most microbiological laboratories will supply the physician treating the patient with a list of antibiotics the VRE are resistant and susceptible to. If the laboratory does not or cannot provide an alternative antibiotic for VRE treatment, the state lab or the CDC should be notified as they may be able to provide additional help and suggestions for treatment.

Linezolid, daptomycin, tigecycline, oritavancin, telavancin, quinupristin-dalfopristin and teicoplanin (not available in the U.S.) are antimicrobials that have been used with success against various VRE strains. Clinicians have also had some success in treating VRE with various combinations of antibiotics. However, VRE antibiotic susceptibility tests done for each infection should help guide the selection of treatment protocols. In addition, consultation with an infectious-disease expert is usually done.

Other procedures can augment the antimicrobial treatment of VRE-infected patients. If there is a collection of pus, such as an abscess, it is important that it be drained. If the infection is associated with an intravenous line, the line should be removed if at all possible. Similarly, it is desirable to remove urinary catheters to facilitate treatment of the urinary tract infection. Patients who are colonized but not infected do not require treatment. There is no established way to eradicate colonization of the stool once it occurs.

People infected with VRE need to be treated by medical caregivers; there is no home remedy for VRE infections.

VRE infections can be cured in most patients, and the outcome is often more dependent on the underlying disease than on the infecting organism. The duration of treatment depends on the site of infection. For example, heart-valve infections may require six weeks of antibiotic therapy. Although the heart valve or other infected site infection is cured of VRE infection, many patients may be still colonized with the organism on mucosal surfaces.

The complications most often seen with VRE infections are sepsis, endocarditis, urinary tract infections, meningitis, and severe wound infections. Early appropriate antibiotic treatment can reduce the severity of these complications; if any complications develop, an infectious-disease consultant is recommended.

The best way to prevent infection is to prevent transmission. This means that hospitals and care facilities must pay meticulous attention to infection-control guidelines to reduce the spread of VRE from patient to patient. Individuals can reduce their risk by washing hands after using the bathroom and before and after touching the mouth or nose. Minimizing the use of intravenous catheters, especially central lines, reduces the risk of VRE sepsis. Similarly, the use of urinary catheters should be minimized and catheters should be removed promptly when no longer needed. Finally, antibiotics should be used only for appropriate indications. Antibiotics are ineffective against viruses and the common cold. There is no vaccine available against VRE.

Caretakers of infected patients should follow good hand hygiene principles. This means washing hands or using alcohol disinfectants on hands before and after touching the patient or objects in the patient's environment. If there is visible soiling of the hands, soap and water should be used rather than alcohol-based disinfectants. If the patient is incontinent of stool or urine, gloves should be used to clean the bed or the patient. However, gloves are not a substitute for good hand hygiene. Simple household disinfectants are effective against VRE and can be used to clean the environment. A 10% bleach solution may also be used.

Hospitals will take additional precautions. Once a patient is known to harbor VRE, whether colonized or infected, the patient will be placed in "contact precautions," usually in a private room. People entering the room will wear a cloth or paper gown over their clothes and use gloves. Again, hand hygiene is critical to reduce spread of the organism. Masks are not needed because VRE is not spread through the air but by direct contact.

Research on VRE is focused on several areas:

• Improving infection-control practices to reduce spread of VRE in health care environments
• The development of new antibiotics to treat VRE (for example, dalbavancin [Dalvance], tedizolid [Sivextro])
• The development of urinary catheters and intravenous catheters that are more resistant to infection
• Basic research aimed at improving our understanding of the bacteria itself and how vancomycin resistance is transferred from species to species

"Vancomycin-Resistant Enterococci in Healthcare Settings," Centers for Disease Control and Prevention
http://www.cdc.gov/HAI/organisms/vre/
vre.html

"Enterococcal Infections: Treatment & Medication," eMedicine.com
http://emedicine.medscape.com/article/
216993-treatment