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Antibiotic resistance is the ability of a microorganism to withstand the effects of an antibiotic. Antibiotic resistance develops through a mutation of the same species. If a bacterium carries several resistance genes, it becomes resistant to multiple antibiotics - multi-resistant, and is informally known as a superbug.
In recent years, bacteria (superbugs) have adapted and can resist multiple antibiotics including the “last-line” drugs. Staphylococcus Aureus bacterium is resistant to the antibiotic methicillin, and is referred to as Methicillin-Resistant Staphylococcus Aureus (usually MRSA). Of the bacteria that have been “colonized” by the human race, MRSA is amongst the most treacherous. To date, there are 17 strains of MRSA with differing degrees of immunity to the effects of various antibiotics. MRSA was first detected in Britain in 1961 and is now “common” in hospitals. Fifty percent of all S. Aureus infections in the US are resistant to penicillin or methicillin, and Vancomycin was considered the only effective antibiotic agent until 1987.
MRSA infections most often occur in patients in hospitals and are rarely seen among the general public. As with ordinary strains of Staphylococcus Aureus, some patients harbor MRSA on their skin or nose without harm whereas other patients may develop infections. Some strains of MRSA are particularly successful at spreading between patients and may also spread between hospitals, presumably when colonized patients or staff visits other hospitals. These strains are known as epidemic MRSA (or EMRSA for short). Although MRSA are resistant to many drugs, most remain susceptible to the antibiotics vancomycin. However, this appears to be changing and we will discuss it at a later section of this course.
In 1987, the first case of VRSA (vancomycin resistant staphylococcus aureus) was reported). VRSA has since been found in hospitals in England, France and the US. (VRSA is also termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin intermediate Staphylococcus aureus) indicating a resistance to all antibiotics).
Several studies have demonstrated that patterns of antibiotic usage greatly affect the number of resistant organisms that develop. The overuse of broad-spectrum antibiotics such as the third generation of Cephalosporins hastens the development of methicillin resistance (MRSA).
Other factors contributing to antibiotic resistance include: incorrect diagnosis, unnecessary prescriptions, improper use of antibiotics by patients, and the use of antibiotics as livestock food additives for growth promotion.
When an outbreak of MRSA infection occurs, an epidemiologic assessment should be initiated to identify risk factors for MRSA acquisition. Within an institution, clinical isolates of MRSA should be saved and submitted for strain typing. Colonized or infected patients should be identified as quickly as possible, appropriate barrier precautions should be instituted, and strict hand washing hygiene should be followed by all medical personnel before and after all patient contacts.
All personnel should be reinstructed on appropriate precautions for patients colonized or infected with multi-resistant microorganisms and on the importance of hand washing in addition to barrier precautions in preventing contact transmission. If tap water is contaminated, water that has been boiled for 10 minutes and filtered to remove particulate matter (if necessary), or chlorinated water—water treated with a dilute bleach solution (sodium hypochlorite) to make the final concentration 0.001% should be used.
If MRSA is judged by a hospital’s infection control program to be of special clinical or epidemiologic significance, then Contact Precautions should be considered. Scrupulous hand washing by hospital staff before and after contact with patients and before any procedure would be required. Patients with MRSA should be physically isolated in a single room or they should be cared for in an area away from other non-infected patients.
Adults infected with HIV may face an increased risk of MRSA infection according to Dr. William Christopher Mathews from University of California, San Diego. He and his colleagues investigated the trends in the incidence of, and risk factors for clinically significant MRSA among 3455 HIV-infected adults treated at their clinic between 2000 and 2003.
During the course of the study, clinical isolates yielding MRSA increased from 2 to 5 per 100 patients, they noted. Sixty percent of the MRSA isolates were community-acquired, the researchers reported in the October 1st issue of the Journal of Acquired Immune Deficiency Syndromes.
Superbugs hence are bacteria that are resistant to most antibiotics. The three main types of superbugs are: MRSA (methicillin-resistant staphylococcus aureus-discussed earlier), VRE (vancomycin-resistant enterococcus), and VRSA (vancomycin resistant staphylococcus aureus).
In 1987, the first case of VRE (Vancomycin-resistant enterococcus) was reported in the United States, and Europe in 1986. VRSA (vancomycin resistant staphylococcus aureus) was first reported in Japan in 1991. VRSA has since been found in hospitals in England, France and the U.S. (VRSA is also termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin intermediate Staphylococcus aureus) indicating a resistance to all antibiotics).
Vancomycin resistance in enterococci (VRE) is among the most dramatic and clinically worrisome examples of resistance to antimicrobial agents in recent years. Enterococci are hardy organisms (bacteria) that can survive under harsh and difficult conditions including high temperature, exposure to some antiseptics, and hypotonic, hypertonic, acidic, and alkaline environments. The emergence of vancomycin-resistant enterococci (VRE) poses a serious threat to certain high-risk patients and populations, challenging the healthcare community to control the spread of this dangerous organism
Vancomycin-resistant enterococci have since been identified in humans worldwide. Resistance happens more frequently when antibiotics are stopped prematurely, or when antibiotics are given empirically before cultures identify a specific organism. Two species of enterococci are responsible for most human enterococcal infections. These are Enterococcus faecalis and Enterococcus faecium. Enterococcus faecalis is the most common species of enterococcus, accounting for 85% to 90% of all enterococcus identified. Enterococcus faecium is less common but it is more likely to develop resistance. Since vancomycin resistance is more commonly found in Enterococcus faecium, it is prudent to monitor closely all clients who have had this organism identified.
VRSA is an acronym for vancomycin resistant staphylococcus aureus whereas VRE is an acronym for vancomycin resistant enterococcus faecalis. The concern about VRE and MRSA in the 1990’s was that VRSA could develop, and in 2002 it did. In June 2002, the first clinically proven case of VRSA was identified as a 40-year old Michigan resident. This patient had co-morbid factors of chronic renal failure, diabetes, and peripheral vascular disease. The patient received extended antibiotic treatment for an infected foot ulcer and subsequently had an amputation of the leg in April 2002. At that time, the patient developed MRSA, and again was treated with multiple antibiotics, including vancomycin.
There is much evidence linking the use of antibiotic therapy to organism resistance and this is especially true for VRE. Healthy individuals who receive a glycopeptide antibiotic, such as vancomycin, frequently become colonized with VRE. Exposure to these antibiotics can cause VRE to emerge by inducing the expression of resistant genes. Antibiotic therapy can also alter the flora of the gastrointestinal tract and create a safe harbor for resistant enterococci to flourish. (DeLisle & Perl, 2003).
As we know, antibiotics work by interfering with the cell processes of bacteria. Some antibiotics work by disrupting the ability of the bacteria to synthesize protein and reproduce. Others work by causing the cell to disintegrate. Vancomycin, gentamycin, erythromycin, tetracycline, and ciprofloxacin are some examples of antibiotics that inhibit protein synthesis. Cefoxitin, cefazolin, and amoxicillin disrupt the membrane of the bacterial cell. (Glover, 2000). Epidemiologists believe that resistance happens when microorganisms are exposed to antibiotics and/or when they acquire genetic factors for resistance from other organisms (plasmids). After an organism becomes resistant, human, animal, or environmental factors can spread the resistant form. Some of these stronger organisms can survive when antibiotics are used—they may even themselves become resistant. As these resistant bacteria reproduce, the resistance is passed to future generations of organisms. Stronger antibiotics are then used to abate the new bacteria—and the cycle repeats.
Hospitals with more than 500 beds have higher rates of VRE. Of the number of enterococci isolated by intensive-care units and reported to the National Nosocomial Infections Surveillance System (NNISS) by December 2000, 26.3% were resistant to vancomycin. That reflected an increase of more than 31% over data from 1995 to1999, and makes enterococci the third most common cause of nosocomial infections in ICUs (DeLisle & Perl, 2003).
The following are examples of the misuse of antibiotics. Attention should be given to reducing this mismanagement.
Healthy people are not likely to acquire VRE or VRSA. Populations at risk for infection with VRE are individuals who are hospitalized and/or have an underlying medical condition that makes them susceptible to infection. These include critically ill patients found in hospital intensive-care units, oncology patients, and renal disease patients (especially those on dialysis).
Patients with severe immune system disorders, patients on vancomycin, patients on multiple antibiotics, and those with extended hospital stays are at risk. Residents in nursing homes and long-term care facilities are also at high risk for VRE infections. Older adults and premature infants are at risk. People who are malnourished, those with chronic diarrhea, and those on multiple antibiotics are also more susceptible to VRE infections (DeLisle & Perl).
The gastrointestinal tract is home for VRE. Colonization usually continues for up to two months, but it has been documented to be present for as long as one year after the client discontinues antibiotics. People who are colonized with VRE can contaminate themselves. Studies have shown that clients who are colonized with VRE can transmit the organism to their own intravenous catheter sites, wound sites, and respirators.
More commonly, however, transmission occurs by healthcare workers. In fact, studies have shown that enterococci have been isolated on the hands of healthcare workers 10% to 43% of the time when these workers are caring for VRE-infected clients. (DeLisle & Perl, 2003).
Nurses as well as other health care workers can spread resistant organisms with hands, clothing, stethoscopes, and other equipment. Nurses may wash their hands thoroughly, but then re-contaminate the hands by touching their own uniforms or lab coats. Surfaces in patients’ rooms may harbor a resistant organism. Countertops, door handles, curtains, and telephones all may be contaminated. Infection-control measures need consistent implementation and special monitoring to be effective.
Identification of specific clusters of infection can lead to the discovery of problems with infection-control practices. Once problems are identified, revised procedures can be put into place to correct them.
Effective surveillance includes counting cases of specific infections, analyzing the data, reporting data to the appropriate people, and creating practices and policies to improve patient care (Friedman & Sexton, 2004).
In contact transmission, which is the way VRE is transmitted, the spread of organisms can occur directly or indirectly. With direct contact, hands touch hands or body surfaces; with indirect contact, organisms are transmitted by contact with a body surface or hands to a contaminated surface or object such as a catheter or stethoscope.
Droplet transmission occurs when large particles are spread via coughing, sneezing, or suctioning. These particles are generally only spread a short distance and are not suspended in the air. Airborne particles, however, consist of droplets that are very small and can remain in the air for extended periods of time.
Common vehicle transmission involves specific microorganisms, such as pseudomonas, that can be spread by contaminated food, water, medications, devices and equipment.
Different types of isolation can be used to prevent the transmission of certain microorganisms. Universal Precautions were introduced in 1985 during the human immunodeficiency virus (HIV) epidemic. In 1996 the Centers for Disease Control and Prevention (CDC) and the Hospital Infection Control Advisory Committee (HICPAC) created a new system of isolation precautions that included Standard Precautions and Transmission-based precautions (Friedman & Sexton, 2004).
Standard Precautions are recommended for all hospitalized patients. Standard Precautions apply to the handling of blood, body fluids, and secretions. Components of Standard Precautions include washing hands thoroughly after each patient contact; use of gloves, gowns, and eye protection with exposure to body secretions; safe disposal of sharp instruments and needles; and correct disposal of soiled linens (Friedman & Sexton, 2004).
Transmission-based precautions are utilized by hospitals and other agencies for clients who have infections that can be spread by contact, droplet, or airborne routes. Contact Precautions are specific to clients who are infected or colonized with VRE, and are designed to prevent transmission directly between persons, or indirectly through surfaces and objects. All healthcare workers are required to use nonsterile gloves for all patient contact, and to wear a gown for any contact that may involve contaminated materials.
Wearing gloves reduces the risk of transmitting organisms, but does not negate the need for good hand hygiene practices. Two important reasons to wear gloves: (1) to provide a barrier of protection between the hands and the contaminated material, and (2) to decrease the spread of microorganisms from the hands to other staff or to objects. Gloves and gowns must be removed before exiting the patient’s room, and hands are to be washed immediately after any patient contact (Friedman & Sexton, 2004). Ideally, patients who are either colonized or infected with VRE should be isolated in a private room. Equipment—such as stethoscopes, thermometers, and other devices that are used routinely—should be dedicated to these clients.
The focus of surveillance programs should be in the ICUs or other areas of concern, such as dialysis units, oncology wards, or nurseries. Dedicated staff should be appointed to care for only VRE-infected or VRE-colonized patients whenever possible. Staff education about VRE, as well as education about specific agency policies, is ongoing and important. The recommendations from the CDC (Centers for Disease Control) suggest that good hand hygiene is the most important measure for reducing the spread of microorganisms
Treatment of VRE should be initiated when infection is confirmed. If the organism is susceptible to antibiotics, then the prescribing clinician should take advantage of available medications. If resistance to antibiotics (including Vancomycin) is confirmed, then the treatment varies based upon the level of resistance.
Treatment is often creative and takes place in combinations of two or more antibiotics. Combinations such as ampicillin and imipenem, ceftriaxone and fosfomycin, and triple-therapy combinations such as ciprofloxacin, gentamicin, and rifampin have been used (Ferris & Kaplan, 2000). Daptomycin is in a class of antibiotics called lipopeptides, and is being used to treat VRE and other gram-positive bacterial infections (Tedesco & Rybak, 2004).
Two main drugs seem to help in the treatment of VRE and other gram-positive pathogens. They are Quinupristin-Dalfopristin (Synercid) and Linezolid. These medications may offer treatment options in clients with drug-resistant strains of infection. Quinupristin-dalfopristin is an injectable antibiotic. Linezolid is in the medication class of oxazolidinones, and targets protein synthesis at the elongation step.
Most providers recognize that the inappropriate use of antibiotics is an important cause of drug resistance. Despite this knowledge, there is still empirical use of vancomycin and other broad-spectrum antibiotics. Some hospitals have instituted “closed” formularies that limit choices of antibiotics. Clinical guidelines for many common infections exist, and they are helpful in selecting the appropriate antibiotic treatment in specified infections.
Some institutions actually restrict the types of antibiotics that can be ordered. Restriction has been effective in decreasing costs as well as reducing the use of broad-spectrum drugs like vancomycin as a first-line drug. .
Rotation of antibiotics (cycling) has been renewed as a preventive practice. This involves rotating antibiotics for treatments. For example, ceftazidime and ciprofloxacin would be cycled in an ICU for treatment of suspected gram-negative infections. Cycling the use of quinolones, fourth-generation cephalosporins, and carbapenems is being studied in some hospital ICUs. This practice may prove to be effective for short periods of time and in closed environments such as intensive-care units (Medscape, 2004).
There are limited treatment options for VRSA infections. Some of the possible options do include rifampin, gentamicin, imipenem, and tetracycline. Patients with S. aureus with reduced susceptibility to vancomycin may be candidates for atimicrobials.
Situations in which vancomycin is deemed appropriate include cases of serious infections caused by beta-lactam–resistant gram-positive organisms, for treatment of infections caused by gram-positive organisms, patients with allergies to beta-lactam antibiotics, or when antibiotic-associated colitis fails to respond to therapy and is life threatening.
Two other appropriate uses for vancomycin are (1) as prophylaxis to prevent endocarditis in clients who are high risk (recommended by the American Heart Association), and (2) as prophylaxis for major surgical procedures involving prosthetic materials and devices that have high rates for Methicillin-Resistant S Aureus (MRSA) (HICPAC, 1995).
The use of vancomycin should be discouraged in cases of:
It is also important to discontinue vancomycin when it is used empirically for presumed infections and final cultures allow for other choices in antibiotics. Vancomycin should not be used as primary treatment of antibiotic-related colitis, routine prophylaxis of low-birth-weight infants, or routine prophylaxis for patients on hemodialysis or peritoneal dialysis.
Educational programs for hospital workers and physicians should include this information, as well as the epidemiology of VRE and the potential impact of this organism on the outcome of clients. Detection and containment of VRE require an aggressive approach to infection control and prescribing practices.
Nurses and other healthcare professionals can help to prevent the development of VRE and other resistant strains of bacteria in several ways. Nurses assist with the management of antibiotic therapy and are instrumental in the proper administration of medications. Nurses can be vigilant about obtaining and reviewing cultures prior to initiation of antibiotic therapy and can monitor correct use.
In hospitals and other agencies, nurses can assist by limiting the transfer and transport of clients who are infected with VRE. Nurses must use appropriate contact isolation precautions and mentor and monitor other providers in correct procedures.
One of most important things that nurses do is educate clients. For example, education should include instructions on proper antibiotic use. This includes knowing the name, dose, and purpose of antibiotic medications and reasons not to share medications with friends or family (Glover, 2000.)
MRSA (methicillin-resistant staphylococcus aureus) is a type of bacteria that is resistant to certain antibiotics. MRSA (a superbug) grows in clusters, multiplies quickly and causes many types of infections from boils to systemic ones. Methycillin was an antibiotic used in the past to treat patients with staphylococcus infections, but after time, it no longer worked. This included use of all penicillins.
MRSA was first detected in Britain in 1961 and is now “common” in hospitals. 17 strains of MRSA with differing degrees of immunity to the effects of various antibiotics exist today, and are treacherous. MRSA has evolved and many strains are now seen inside and outside of the hospital.
Vancomycin-resistant enterococci (VRE) has emerged as a serious challenge to healthcare providers in the United States. Enterococcus is a bacterium in the gastrointestinal and genital tracts, which is highly aggressive especially in the post- operative hospitalized patients. Among the diseases caused are urinary tract infections, septicemia, and endocarditis.
VRSA is worst yet. In the 1990’s it was speculated that VRE and MRSA could lead to VRSA which is exactly what happened in Japan in the late 1990’s and in 2002, with a patient who had co-morbid factors in Michigan.
The development and use of antimicrobial agents has been instrumental in treating infections and saving lives. Organisms such as enterococci have found ways to develop resistance against the antibiotics that have destroyed them in the past. Organisms are able to transfer their genetic material and resistance to other organisms and create newer generations of resistant bacteria. Nurses are once again placed in a key role to prevent spread through patient education.