Methicillin resistant staphylococcus aureus

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Related articles: Methicillin-resistant staphylococcus aureus

Overview
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Methicillin-resistant Staphylococcus Aureus (MRSA) is a type of staph that is resistant to certain antibiotics. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin and amoxicillin. Staph infections, including MRSA, occur most frequently among persons in hospitals and healthcare facilities (such as nursing homes and dialysis centers) who have weakened immune systems (see healthcare-associated MRSA).

MRSA infections that are acquired by persons who have not been recently (within the past year) hospitalized or had a medical procedure (such as dialysis, surgery, catheters) are known as CA-MRSA infections. Staph or MRSA infections in the community are usually manifested as skin infections, such as pimples and boils, and occur in otherwise healthy people.

Epidemiology and Demographics


Worldwide, an estimated 2 billion people carry some form of S. aureus; of these, up to 53 million (2.7% of carriers) are thought to carry MRSA. In the United States, 95 million carry S. aureus in their noses; of these 2.5 million (2.6% of carriers) carry MRSA. A population review conducted in 3 communities in the US showed the annual incidence of CA-MRSA during 2001–2002 to be 18–25.7/100,000 ; most CA-MRSA isolates were associated with clinically relevant infections, and 23% of patients required hospitalization.

Because cystic fibrosis patients are often treated with multiple antibiotics in hospital settings, they are often colonised with MRSA, potentially increasing the rate of life-threatening MRSA pneumonia in this group. The risk of cross-colonisation has led to increased use of isolation protocols among these patients. In a hospital setting, patients who have received fluoroquinolones are more likely to become colonised with MRSA, this is probably because many circulating strains of MRSA are fluoroquinolone-resistant, which means that MRSA is able to colonise patients whose normal skin flora have been cleared of non-resistant S. aureus by fluoroquinolones.

In the USA, reports have been increasing of outbreaks of MRSA colonisation and infection through skin contact in locker rooms and gymnasiums, even among healthy populations. MRSA also is becoming a problem in paediatrics, including hospital nurseries. A 2007 study found that 4.6% of patients in US healthcare facilities were infected or colonized with MRSA.

MRSA causes as many as 20% of Staphylococcus aureus infections in populations that use intravenous drugs. These out-of-hospital strains of MRSA, now designated as community-acquired, methicillin-resistant Staphylococcus aureus, or CA-MRSA, are more easily treated than hospital-acquired MRSA (although more virulent than MSSA). CA-MRSA apparently did not evolve de novo in the community, but represents a hybrid between MRSA which escaped from the hospital environment and the once easily treatable community organisms. Most of the hybrid strains also acquired a virulence factor which makes their infections invade more aggressively, resulting in deep tissue infections following minor scrapes and cuts, and many cases of fatal pneumonia as well.

As of early 2005, the number of deaths in the United Kingdom attributed to MRSA has been estimated by various sources to lie in the area of 3000 per year. Staphylococcus bacteria account for almost half of all UK hospital infections. The issue of MRSA infections in hospitals has recently been a major political issue in the UK, playing a significant role in the debates over health policy in the United Kingdom general election held in 2005.

During the summer of 2005, researchers in The Netherlands discovered that three pig farmers or their families were infected by MRSA bacteria that were also found on their pigs. Researchers from Radboud University Nijmegen are now investigating how widespread the MRSA bacteria is in pigs, and whether it will become characterised among the zoonoses.

Recently, it has been observed that MRSA can replicate inside of Acanthamoeba, increasing MRSA numbers 1000-fold. Since Acanthamoeba can form cysts easily picked up by air currents, these organisms can spread MRSA via airborne routes. Whether control of Acanthamoeba in the clinical environment will also help to control MRSA, remains an area for research.

Strains

In the UK, the most common strains are EMRSA15 and EMRSA16.[45] EMRSA16 is the best described epidemiologically: it originated in Kettering, England, and the full genomic sequence of this strain has been published. This has been recognised as being identical to the ST36:USA200 strain which circulates in the USA, and carries the SCCmec type II, enterotoxin A and toxic shock syndrome toxin 1 genes. Under the new international typing system, this strain is now called MRSA252 and the entire genome sequence of this strain has been published. It is not entirely certain why this strain has become so successful, whereas previous strains have failed to persist: one explanation is the characteristic pattern of antibiotic sensitivities. Both the EMRSA-15 and -16 strains are resistant to erythromycin and ciprofloxacin: It is known that Staphylococcus aureus can survive intracellularly, and these are precisely the antibiotics that best penetrate intracellularly: it may be that these strains of S. aureus are therefore able to exploit an intracellular niche.

In the USA, the epidemic of community-associated MRSA is due to a CC8 strain designated ST8:USA300, which carries mec type IV, Panton-Valentine leukocidin, and enterotoxins Q and K. Other community-associated strains of MRSA are ST8:USA500 and ST59:USA1000.

How MRSA Spreads in Healthcare Settings:

The main mode of transmission to other patients is through human hands, especially healthcare workers' hands. Hands may become contaminated with MRSA bacteria by contact with infected or colonized patients. If appropriate hand hygiene such as washing with soap and water or using an alcohol-based hand sanitizer is not performed, the bacteria can be spread when the healthcare worker touches other patients.

MRSA: a Growing Problem in the Healthcare Setting, But One with a Cure

MRSA is becoming more prevalent in healthcare settings. According to CDC data, the proportion of infections that are antimicrobial resistant has been growing. In 1974, MRSA infections accounted for two percent of the total number of staph infections; in 1995 it was 22%; in 2004 it was some 63%.

The good news is that MRSA is preventable. The first step to prevent MRSA, is to prevent healthcare infections in general. Infection control guidelines produced by CDC and the Healthcare Infection Control and Prevention Advisory Committee (HICPAC) are central to the prevention and control of healthcare infections and ultimately, MRSA in healthcare settings. To learn more about infection control guidelines to prevent infections and MRSA go to http://www.cdc.gov/ncidod/dhqp. CDC welcomes the increased attention and dialogue on the important problem of MRSA in healthcare. CDC, state and local health departments and partners nationwide are collaborating to prevent MRSA infections in healthcare settings. For example, CDC


 * monitors trends in infections and MRSA through surveillance systems such as the National Healthcare Safety Network, formerly the National Nosocomial Infection Surveillance System and the Dialysis Surveillance Network to identify which patients are at highest risk and where prevention efforts should be targeted.
 * works with multiple prevention partners including state health departments, academic medical centers, and regional and national collaboratives to identify and promote effective strategies to prevent MRSA transmission.
 * developed an overarching strategy to help guide healthcare facilities to control antibiotic resistance called The Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. This campaign includes specific strategies for various healthcare populations, including hospitalized adults and children, dialysis patients, surgical patients, and long-term care patients.

Risk Factors
MRSA occurs most frequently among patients who undergo invasive medical procedures or who have weakened immune systems and are being treated in hospitals and healthcare facilities such as nursing homes and dialysis centers.

Screening
The National Committee for Clinical Laboratory Standards (NCCLS), now called the Clinical and Laboratory Standards Institute (CLSI), recommends the cefoxitin disk screen test, the latex agglutination test for PBP2a, or a plate containing 6 μg/ml of oxacillin in Mueller-Hinton agar supplemented with NaCl (4% w/v; 0.68 mol/L) as alternative methods of testing for MRSA. For methods of inoculation, see CLSI Approved Standard M100-S15.

Pathophysiology & Etiology
Staphylococcus aureus became methicillin resistant by acquiring a mecA gene, usually carried on a larger piece of DNA called a staphylococcal cassette chromosome SCCmec.

Natural History
Staphylococcus aweus remains an important cause of nosocomial infection, especially nosocomial pneumonia, surgical wound infection, and bloodstream infection. Methicillin-resistant S aureus (MRSA) first emerged as an important clinical problem in the United Kingdom in the early 196Os, shortly after methicillin came into clinical use. Although MRSA was first recognized in the United States in 1961, it was not until the late 1960s that reports of outbreak investigations began to appear in the U.S. medical literature.

Most of the sources of data on the prevalence and distribution of MRSA in the United States are reports of outbreak investigations and surveys of hospitals and laboratories, including pediatric and Veterans Affairs hospitals. MRSA outbreaks have been reported from all U.S. geographic regions, although a wide variation in the geographic distribution of MRSA isolates appears to exist.

Several reports also have suggested an increasing prevalence of MRSA in U.S. hospitals. However, some of these reports provide no information on current trends. The most recent report by Boyce was based on a questionnaire survey of U.S. hospital epidemiologists during 1987-1989. In addition, all these reports covered relatively limited time periods.

The National Nosocomial Infections Surveillance (NNIS) System, which began in 1970, is the only source of national information on nosocomial infections in the United States. One of the objectives of the NNIS System is to identify changes in nosocomial pathogens and antimicrobial resistance. To determine whether the proportion of S aureus resistant to methicillin has increased over a 17-year period, 1975 through 1991, we analyzed NNIS data in which S aureus was associated with a nosocomial infection.

Diagnosis
According to Betsy McCaughey, founder of the Committee to Reduce Infection Deaths, MRSA can be detected in asymptomatic patients by a blood test. Combined with extra sanitary measures for those in contact with infected patients, screening patients admitted to hospitals has been found effective in minimizing spread of MRSA in hospitals in Denmark, Finland and the Netherlands.

Is it difficult to detect oxacillin/methicillin resistance?

Accurate detection of oxacillin/methicillin resistance can be difficult due to the presence of two subpopulations (one susceptible and the other resistant) that may coexist within a culture of staphylococci. All cells in a culture may carry the genetic information for resistance, but only a small number may express the resistance in vitro. This phenomenon is termed heteroresistance and occurs in staphylococci resistant to penicillinase-stable penicillins, such as oxacillin.

Cells expressing heteroresistance grow more slowly than the oxacillin-susceptible population and may be missed at temperatures above 35°C. This is why CLSI recommends incubating isolates being tested against oxacillin, methicillin, or nafcillin at 33-35° C (maximum of 35°C) for a full 24 hours before reading.

History and Symptoms
S. aureus most commonly colonises the anterior nares (the nostrils) although the respiratory tract, open wounds, intravenous catheters and urinary tract are also potential sites for infection. MRSA infections are usually asymptomatic in healthy individuals and may last from a few weeks to many years.

Many people who are symptomatic present with pus-filled boils, and occasionally with rashes.

Risk Stratification and Prognosis
MRSA in healthcare settings commonly causes serious and potentially life threatening infections, such as bloodstream infections, surgical site infections, or pneumonia.

It has been difficult to quantify the degree of morbidity and mortality attributable to MRSA. Patients with S. aureus infection had, on average, 3 times the length of hospital stay (14.3 vs 4.5 days), 3 times the total charges ($48,824 vs $14,141), and 5 times the risk of in-hospital death (11.2% vs 2.3%) than inpatients without this infection. Cosgrove et al, in a meta-analysis of 31 studies, conclude that bacteremia as a result of MRSA is associated with an increased mortality compared with MSSA bacteraemia with an odds ratio of 1.93 (95% CI, 1.54±2.42; In addition, Wyllie et al. report a death rate of 34% within 30 days among patients infected with MRSA, while among MSSA patients the death rate was similar at 27%.

The major issue is that there are a number of factors that can lead to someone's death, and it is believed that patients with MRSA bacteraemia are sicker and will consequently have a higher mortality because of their underlying illness. However, several studies including one by Blot and colleagues that have adjusted for underlying disease still found MRSA bacteraemia to have a higher attributable mortality than MSSA bacteraemia.[11]

Treatment
Community-acquired MRSA often results in abscess formation that requires incision and drainage to treat. Prior to ca-MRSA, abscesses were not considered contagious (it was assumed that violation of skin integrity with introduction of staph from normal skin colonization was required). However, newly emerging ca-MRSA is transmissible (similar, but with very important differences) from hospital-acquired MRSA. ca-MRSA is less likely to cause cellulitis than other forms of MRSA.

Both ca-MRSA and ha-MRSA are resistant to traditional anti-staph beta lactam antibiotics, eg cephalexin. ca-MRSA has a greater sensitivity spectrum that includes sulfa drugs, tetracyclines, and clindamycin. ha-MRSA is resistant to even those antibiotics and often only sensitive to vancomycin. Newer drugs such as linezolid (newer oxazolidinones class) may be effective against both ca-MRSA and ha-MRSA.

On 18 May 2006, a team of researchers from Merck Pharmaceuticals published in Nature that they had discovered an entirely new type of antibiotic, called platensimycin, and they have demonstrated that it can be used successfully to fight MRSA.[24][25]

An entirely different and promising approach is phage therapy (e.g., at the Tbilisi Institute in Georgia), which reports efficacy against up to 95% of tested Staphylococcus isolates.

Raw honey dressings are also being successfully used for prevention and treatment of MRSA.

It has been reported that use of maggots to treat an MRSA infection has been successful. Studies have been done on diabetic patients and the treatment time has been significantly less than that of other standard treatments.

Acute Pharmacotherapies
Vancomycin and teicoplanin are glycopeptide antibiotics used to treat MRSA infections. Teicoplanin is a structural congener of vancomycin that has a similar activity spectrum, but a longer half-life (t½). The oral absorption of vancomycin and teicoplanin is very low and must be administered intravenously in order to control systematic infections. One of the problems with vancomycin is not just that its route of administration is inconvenient, but also that it is inferior in terms of its efficacy compared to antistaphylococcal penicillins.

Several new strains of MRSA have been found showing antibiotic resistance even to vancomycin and teicoplanin; those new evolutions of the MRSA bacteria are dubbed vancomycin intermediate-resistant Staphylococcus aureus (VISA). Linezolid, quinupristin/dalfopristin, daptomycin, tigecycline are used to treat more severe infections that do not respond to the glycopeptides such as vancomycin. MRSA infections can be treated with oral agents such as linezolid, rifampicin+fusidic acid, rifampicin+fluoroquinolone, pristinamycin, co-trimoxazole (trimethoprim-sulfamethoxazole), doxycycline or minocycline, and clindamycin.

Primary Prevention
Standard Precautions include:


 * Handwashing
 * Wash hands after touching blood, body fluids, secretions, excretions, and contaminated items, whether or not gloves are worn.
 * Wash hands immediately after gloves are removed, between patient contacts, and when otherwise indicated to avoid transfer of microorganisms to other patients or environments. It may be necessary to wash hands between tasks and procedures on the same patient to prevent cross-contamination of different body sites.


 * Gloving: Wear gloves (clean nonsterile gloves are adequate) when touching blood, body fluids, secretions, excretions, and contaminated items; put on clean gloves just before touching mucous membranes and nonintact skin. Remove gloves promptly after use, before touching noncontaminated items and environmental surfaces, and before going to another patient, and wash hands immediately to avoid transfer of microorganisms to other patients or environments.


 * Masking: Wear a mask and eye protection or a face shield to protect mucous membranes of the eyes, nose, and mouth during procedures and patient-care activities that are likely to generate splashes or sprays of blood, body fluids, secretions, and excretions.


 * Gowning: Wear a gown (a clean nonsterile gown is adequate) to protect skin and prevent soiling of clothes during procedures and patient-care activities that are likely to generate splashes or sprays of blood, body fluids, secretions, and excretions or cause soiling of clothing.


 * Appropriate device handling: Handle used patient-care equipment soiled with blood, body fluids, secretions, and excretions in a manner that prevents skin and mucous membrane exposures, contamination of clothing, and transfer of microorganisms to other patients and environments. Ensure that reusable equipment is not used for the care of another patient until it has been appropriately cleaned and reprocessed and that single-use items are properly discarded.


 * Appropriate handling of laundry: Handle, transport, and process used linen soiled with blood, body fluids, secretions, and excretions in a manner that prevents skin and mucous membrane exposures, contamination of clothing, and transfer of microorganisms to other patients and environments.

If MRSA is judged by the hospital's infection control program to be of special clinical or epidemiologic significance, then Contact Precautions should be considered.

Contact Precautions consist of:


 * 1) Placing a patient with MRSA in a private room. When a private room is not available, the patient may be placed in a room with a patient(s) who has active infection with MRSA, but with no other infection (cohorting).
 * 2) Wearing gloves (clean nonsterile gloves are adequate) when entering the room. During the course of providing care for a patient, change gloves after having contact with infective material that may contain high concentrations of microorganisms (e.g., fecal material and wound drainage). Remove gloves before leaving the patient's room and wash hands immediately with an antimicrobial agent. After glove removal and handwashing, ensure that hands do not touch potentially contaminated environmental surfaces or items in the patient's room to avoid transfer of microorganisms to other patients and environments.
 * 3) Wearing a gown when entering the room if you anticipate that your clothing will have substantial contact with the patient, environmental surfaces, or items in the patient's room, or if the patient is incontinent, or has diarrhea, an ileostomy, a colostomy, or wound drainage not contained by a dressing. Remove the gown before leaving the patient's room. After gown removal, ensure that clothing does not contact potentially contaminated environmental surfaces to avoid transfer of microorganisms to other patients and environments.
 * 4) Limiting the movement and transport of the patient from the room to essential purposes only. If the patient is transported out of the room, ensure that precautions are maintained to minimize the risk of transmission of microorganisms to other patients and contamination of environmental surfaces or equipment.
 * 5) Ensuring that patient-care items, bedside equipment, and frequently touched surfaces receive daily cleaning.
 * 6) When possible, dedicating the use of noncritical patient-care equipment and items such as stethoscope, sphygmomanometer, bedside commode, or electronic rectal thermometer to a single patient (or cohort of patients infected or colonized with MRSA) to avoid sharing between patients. If use of common equipment or items is unavoidable, then adequately clean and disinfect them before use on another patient.

Secondary Prevention
Culturing of Personnel and Management of Personnel Carriers of MRSA:

Unless the objective of the hospital is to eradicate all MRSA carriage and treat all personnel who are MRSA carriers, whether or not they disseminate MRSA, it may be prudent to culture only personnel who are implicated in MRSA transmission based on epidemiologic data. MRSA-carrier personnel who are epidemiologically linked to transmission should be removed from direct patient care until treatment of the MRSA-carrier status is successful. If the hospital elects to culture all personnel to identify MRSA carriers, a) surveillance cultures need to be done frequently, and b) it is likely that personnel colonized by MRSA who are not linked to transmission and/or who may not be MRSA disseminators will be identified, subjected to treatment, and/or removed from patient contact unnecessarily. Because of the high cost attendant to repeated surveillance cultures and the potential of repeated culturing to result in serious consequences to health care workers, hospitals should weigh the advantages and the adverse effects of routinely culturing personnel before doing so.

Control of MRSA Outbreaks:

When an outbreak of MRSA infection occurs, an epidemiologic assessment should be initiated to identify risk factors for MRSA acquisition in the 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 handwashing by medical personnel before and after all patient contacts should be strictly adhered to.

All personnel should be reinstructed on appropriate precautions for patients colonized or infected with multiresistant microorganisms and on the importance of handwashing and barrier precautions in preventing contact transmission.

If additional help is needed by the hospital, a consultation with the local or state health department or CDC may be necessary.