Methicillin-resistant Staphylococcus aureus
|Methicillin-resistant Staphylococcus aureus|
|Scanning electron micrograph of a human neutrophil ingesting MRSA|
Methicillin-resistant Staphylococcus aureus (MRSA) (// or //) is a gram-positive bacterium that is genetically different from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. MRSA is any strain of S. aureus that has developed, through horizontal gene transfer and natural selection, multiple drug resistance to beta-lactam antibiotics. β-lactam antibiotics are a broad spectrum group which includes some penams – penicillin derivatives such as methicillin and oxacillin, and cephems such as the cephalosporins. Strains unable to resist these antibiotics are classified as methicillin-susceptible Staphylococcus aureus, or MSSA.
MRSA is prevalent in hospitals, prisons, and nursing homes, where people with open wounds, invasive devices such as catheters, and weakened immune systems are at greater risk of nosocomial infection (hospital-acquired infection). MRSA began as a hospital-acquired infection, but has developed limited endemic status and is now community-acquired as well as livestock-acquired. The terms HA-MRSA (healthcare-associated or hospital-acquired MRSA), CA-MRSA (community-associated MRSA) and LA-MRSA (livestock-associated) reflect this distinction.
- 1 Microbiology
- 2 Signs and symptoms
- 3 Risk factors
- 4 Diagnosis
- 5 Genetics
- 6 Prevention
- 7 Treatment
- 8 Epidemiology
- 9 History
- 10 Research
- 11 Additional images
- 12 In popular culture
- 13 See also
- 14 References
- 15 Further reading
Like all Staphylococcus aureus (usually S. aureus but abbreviated SA at times), methicillin-resistant Staphylococcus aureus (MRSA) is a gram-positive, spherical (coccus) bacterium that is about 1 micron in diameter. It does not form spores and it is non-motile. It forms grape-like clusters or chains.:390 Unlike Methicillin-susceptible Staphylococcus aureus MSSA, MRSA is slower growing on a variety of media and has been found to exist in mixed colonies of MSSA. The mecA gene, which confers the resistance to a number of antibiotics is present in MRSA and not in MSSA. In some instances, the mecA gene is present in MSSA but is not expressed. Polymerase chain reaction (PCR) testing is the most precise method in identifying MRSA strains. Specialized culture media have been developed to better differentiate between MSSA and MRSA and in some cases, it will identify specific strains that are resistant to different antibiotics.:402 Other strains of S. aureus have emerged that are resistant to oxacillin, clindamycin, teicoplanin, and erythromycin. These resistant strains may or may not possess the mecA gene. S. aureus has also developed resistance to vancomycin (VRSA). One strain is only partially susceptible to vancomycin and is called vancomycin-intermediate S. aureus (VISA). GISA is a strain of resistant S. aureus and stands for glycopeptide-intermediate S. aureus and is less suspectible to vancomycin and teicoplanin. Resistance to antibiotics in S. aureus can be quantified. This done by determining the amount of the antibiotic in micrograms/milliliter must be used to inhibit growth. If S. aureus is inhibited at a concentration of vancomycin of less than or equal to 4 micrograms/milliliter, it is said to be susceptible. If a concentration of greater than 32 micrograms/milliliter is necessary to inhibit growth, it is said to be resistant.:637
Signs and symptoms
In humans, S. aureus is part of the normal microbiota present in the upper respiratory tract, and on skin and in the gut mucosa. S. aureus, along with similar species that can colonize and act symbiotically but can cause disease if they begin to take over the tissues they have colonized or invade other tissues, have been called "pathobionts".
After 72 hours, MRSA can take hold in human tissues and eventually become resistant to treatment. The initial presentation of MRSA is small red bumps that resemble pimples, spider bites, or boils; they may be accompanied by fever and, occasionally, rashes. Within a few days, the bumps become larger and more painful; they eventually open into deep, pus-filled boils About 75 percent of CA-MRSA infections are localized to skin and soft tissue and usually can be treated effectively.
Some of the populations at risk:
- People with indwelling implants, prostheses, drains, and catheters
- People who are frequently in crowded places, especially with shared equipment and skin-to-skin contact
- People with weak immune systems (HIV/AIDS, lupus, or cancer sufferers; transplant recipients, severe asthmatics, etc.)
- Intravenous drug users
- Users of quinolone antibiotics
- The elderly
- School children sharing sports and other equipment.
- College students living in dormitories
- People staying or working in a health care facility for an extended period of time
- People who spend time in coastal waters where MRSA is present, such as some beaches in Florida and the west coast of the United States
- People who spend time in confined spaces with other people, including occupants of homeless shelters, prison inmates, military recruits in basic training,
- Veterinarians, livestock handlers, and pet owners
- Those that ingest unpasteurized milk
- Those who are immunocompromised and also colonized:249
- Those with Chronic obstructive pulmonary disease
- Those who had thoracic surgery.
As many as 22% of those infected with MRSA do not have any discernable risk factors.:637
People who are hospitalized, including the elderly, are often immunocompromised and susceptibility to infection of all kinds, including MRSA; when the infection is by MRSA this is called healthcare-associated or hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA).
Surgical as well as nonsurgical wounds can be infected with HA-MRSA. Surgical site infections (SSI) occur on the skin surface but can spread to internal organs and blood to cause sepsis. Transmission occurs between healthcare providers and patients. This is because some providers may inconsistently neglect to perform hand-washing between examinations.
Prison inmates, military recruits
Prisons, and military barracks, can be crowded and confined, and poor hygiene practices may proliferate, thus putting inhabitants at increased risk of contracting MRSA. Cases of MRSA in such populations were first reported in the United States, and then in Canada. The earliest reports were made by the Center for Disease Control (CDC) in US state prisons. In the news media, hundreds of reports of MRSA outbreaks in prisons appeared between 2000 and 2008. For example, in February 2008, the Tulsa County jail in Oklahoma started treating an average of 12 S. aureus cases per month. A report on skin and soft tissue infections in the Cook County jail in Chicago in 2004–05 demonstrated MRSA was the most common cause of these infections among cultured lesions, and few risk factors were more strongly associated with MRSA infections than infections caused by methicillin-susceptible S. aureus. In response to these and many other reports on MRSA infections among incarcerated and recently incarcerated persons, the Federal Bureau of Prisons has released guidelines for the management and control of the infections, although few studies provide an evidence base for these guidelines. During a recent study in Fort Benning Georgia, a variety of military recruits both healthy and those suffering from soft tissue infections were tested for MRSA as well as other pathogens. The researchers determined that a significant portion of trainees were either asymptomatic carriers of MRSA or that MRSA was the cause of their infection.
Domestic pets are susceptible to MRSA infection from their owners; MRSA infected pets can also transmit MRSA to humans.
Locker rooms, gyms, and related athletic facilities offer potential sites for MRSA contamination and infection. Athletes have been identified as a high risk group. A study linked MRSA to the abrasions caused by artificial turf. Three studies by the Texas State Department of Health found the infection rate among football players was 16 times the national average. In October 2006, a high-school football player was temporarily paralyzed from MRSA-infected turf burns. His infection returned in January 2007 and required three surgeries to remove infected tissue, as well as three weeks of hospital stay. In 2013, Lawrence Tynes, Carl Nicks, and Johnthan Banks of the Tampa Bay Buccaneers were diagnosed with MRSA. Tynes and Nicks apparently did not contract the infection from each other, but it is unknown if Banks contracted it from either individual. In 2015, Los Angeles Dodgers' infielder Justin Turner was infected while the team visited the New York Mets. In October 2015, New York Giants tight end Daniel Fells was hospitalized with a serious MRSA infection.
MRSA is becoming a critical problem in pediatric settings; recent studies found 4.6% of patients in U.S. health-care facilities, (presumably) including hospital nurseries, were infected or colonized with MRSA. Children (and adults, as well) who come in contact with day-care centers, playgrounds, locker rooms, camps, dormitories, classrooms and other school settings, and gyms and workout facilities are at higher risk of getting MRSA. Parents should be especially cautious of children who participate in activities where sports equipment is shared, such as football helmets and uniforms.
Diagnostic microbiology laboratories and reference laboratories are key for identifying outbreaks of MRSA. Normally, the bacterium must be cultured from blood, urine, sputum, or other body-fluid samples, and in sufficient quantities to perform confirmatory tests early-on. Still, because no quick and easy method exists to diagnose MRSA, initial treatment of the infection is often based upon 'strong suspicion' and techniques by the treating physician; these include quantitative PCR procedures, which are employed in clinical laboratories for quickly detecting and identifying MRSA strains.
Another common laboratory test is a rapid latex agglutination test that detects the PBP2a protein. PBP2a is a variant penicillin-binding protein that imparts the ability of S. aureus to be resistant to oxacillin.
Antimicrobial resistance is genetically based; resistance is mediated by the acquisition of extrachromosomal genetic elements containing resistance genes. Examples include plasmids, transposable genetic elements, and genomic islands, which are transferred between bacteria through horizontal gene transfer. A defining characteristic of MRSA is its ability to thrive in the presence of penicillin-like antibiotics, which normally prevent bacterial growth by inhibiting synthesis of cell wall material. This is due to a resistance gene, mecA, which stops β-lactam antibiotics from inactivating the enzymes (transpeptidases) critical for cell wall synthesis.
Staphylococcal cassette chromosome mec (SCCmec) is a genomic island of unknown origin containing the antibiotic resistance gene mecA. SCCmec contains additional genes beyond mecA, including the cytolysin gene psm-mec, which may suppress virulence in HA-acquired MRSA strains. In addition this locus encodes strain dependent gene regulatory RNA called psm-mecRNA. SCCmec also contains ccrA and ccrB; both genes encode recombinases that mediate the site-specific integration and excision of the SCCmec element from the S. aureus chromosome. Currently, six unique SCCmec types ranging in size from 21–67 kb have been identified; they are designated types I-VI and are distinguished by variation in mec and ccr gene complexes. Owing to the size of the SCCmec element and the constraints of horizontal gene transfer, a minimum of five clones are thought to be responsible for the spread of MRSA infections, with clonal complex (CC) 8 most prevalent. SCCmec is thought to have originated in the closely related Staphylococcus sciuri species and transferred horizontally to S. aureus. 
Different SCCmec genotypes confer different microbiological characteristics, such as different antimicrobial resistance rates. Different genotypes are also associated with different types of infections. Types I-III SCCmec are large elements that typically contain additional resistance genes and are characteristically isolated from HA-MRSA strains. Conversely, CA-MRSA is associated with types IV and V, which are smaller and lack resistance genes other than mecA.
These distinctions were thoroughly investigated by Collins et al. in 2001 and can be explained by the fitness differences associated with carriage of a large or small SCCmec plasmid. Carriage of large plasmids, such as SCCmecI-III, is costly to the bacteria, resulting in compensatory decrease in virulence expression. MRSA is able to thrive in hospital settings with increased antibiotic resistance but decreased virulence- HA-MRSA targets immunocompromised, hospitalized hosts, thus a decrease in virulence is not maladaptive. In contrast, CA-MRSA tends to carry lower fitness cost SCCmec elements to offset the increased virulence and toxicity expression required to infect healthy hosts.
mecA is a biomarker gene responsible for resistance to methicillin and other β-lactam antibiotics. After acquisition of mecA, the gene must be integrated and localized in the S. aureus chromosome. mecA encodes penicillin-binding protein 2a (PBP2a), which differs from other penicillin-binding proteins as its active site does not bind methicillin or other β-lactam antibiotics. As such, PBP2a can continue to catalyze the transpeptidation reaction required for peptidoglycan cross-linking, enabling cell wall synthesis in the presence of antibiotics. As a consequence of the inability of PBP2a to interact with β-lactam moieties, acquisition of mecA confers resistance to all β-lactam antibiotics in addition to methicillin.
mecA is under the control of two regulatory genes, mecI and mecR1. MecI is usually bound to the mecA promoter and functions as a repressor. In the presence of a β-lactam antibiotic, MecR1 initiates a signal transduction cascade that leads to transcriptional activation of mecA. This is achieved by MecR1-mediated cleavage of MecI, which alleviates MecI repression. mecA is further controlled by two co-repressors, BlaI and BlaR1. blaI and blaR1 are homologous to mecI and mecR1, respectively, and normally function as regulators of blaZ, which is responsible for penicillin resistance. The DNA sequences bound by MecI and BlaI are identical; therefore, BlaI can also bind the mecA operator to repress transcription of mecA.
Arginine catabolic mobile element
The arginine catabolic mobile element (ACME) is a virulence factor present in many MRSA strains but not prevalent in MSSA. SpeG-positive ACME compensates for the polyamine hypersensitivity of S. aureus and facilitates stable skin colonization, wound infection, and person-to-person transmission.
Acquisition of SCCmec in methicillin-sensitive staphylococcus aureus (MSSA) gives rise to a number of genetically different MRSA lineages. These genetic variations within different MRSA strains possibly explain the variability in virulence and associated MRSA infections. The first MRSA strain, ST250 MRSA-1 originated from SCCmec and ST250-MSSA integration. Historically, major MRSA clones: ST2470-MRSA-I, ST239-MRSA-III, ST5-MRSA-II, and ST5-MRSA-IV were responsible for causing hospital-acquired MRSA (HA-MRSA) infections. ST239-MRSA-III, known as the Brazilian clone, was highly transmissible compared to others and distributed in Argentina, Czech Republic, and Portugal.
In the UK, the most common strains of MRSA are EMRSA15 and EMRSA16. EMRSA16 has been found to be identical to the ST36:USA200 strain, which circulates in the United States, and to carry 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. EMRSA 15 is also found to be one of the common MRSA strains in Asia. Other common strains include ST5:USA100 and EMRSA 1. These strains are genetic characteristics of HA-MRSA.
Community-acquired MRSA (CA-MRSA) strains emerged in late 1990 to 2000, infecting healthy people who had not been in contact with health care facilities. Researchers suggest that CA-MRSA did not evolve from the HA-MRSA. This is further proven by molecular typing of CA-MRSA strains and genome comparison between CA-MRSA and HA-MRSA, which indicate that novel MRSA strains integrated SCCmec into MSSA separately on its own. By mid 2000, CA-MRSA was introduced into the health care systems and distinguishing CA-MRSA from HA-MRSA became a difficult process. Community-acquired MRSA (CA-MRSA) is more easily treated and more virulent than hospital-acquired MRSA (HA-MRSA). The genetic mechanism for the enhanced virulence in CA-MRSA remains an active area of research. Especially the Panton–Valentine leukocidin (PVL) genes are of interest because they are a unique feature of CA-MRSA.
In the United States, most cases of CA-MRSA are caused by a CC8 strain designated ST8:USA300, which carries SCCmec type IV, Panton–Valentine leukocidin, PSM-alpha and enterotoxins Q and K, and ST1:USA400. The ST8:USA300 strain results in skin infections, necrotizing fasciitis and toxic shock syndrome, whereas the ST1:USA400 strain results in necrotizing pneumonia and pulmonary sepsis. Other community-acquired strains of MRSA are ST8:USA500 and ST59:USA1000. In many nations of the world, MRSA strains with different predominant genetic background types have come to predominate among CA-MRSA strains; USA300 easily tops the list in the U.S. and is becoming more common in Canada after its first appearance there in 2004. For example, in Australia ST93 strains are common, while in continental Europe ST80 strains, which carry SCCmec type IV, predominate. In Taiwan, ST59 strains, some of which are resistant to many non-beta-lactam antibiotics, have arisen as common causes of skin and soft tissue infections in the community. In a remote region of Alaska, unlike most of the continental U.S., USA300 was found rarely in a study of MRSA strains from outbreaks in 1996 and 2000 as well as in surveillance from 2004–06.
A MRSA strain, CC398, is found in intensively reared production animals (primarily pigs, but also cattle and poultry), where it can be transmitted to humans as LA-MRSA (livestock-associated MRSA).
In health care settings, isolating those with MRSA from those without the infection, is one method to prevent transmission. Rapid culture and sensitivity testing and molecular testing identifies carriers and reduces infection rates.
MRSA can be identified by swabbing the nostrils and isolating the bacteria found inside the nostrils. Combined with extra sanitary measures for those in contact with infected people, swab screening people admitted to hospitals has been found to be effective in minimizing the spread of MRSA in hospitals in the United States, Denmark, Finland, and the Netherlands.
The CDC offers suggestions for preventing the contraction and spread MRSA infection which are applicable to those in community settings, including incarcerated populations, childcare center employees, and athletes. To prevent the spread of MRSA the recommendations are to wash hands using soap and water or an alcohol-based sanitizer. Additional recommendations are to keep wounds clean and covered, avoid contact with other people's wounds, avoid sharing personal items such as razors or towels, shower after exercising at athletic facilities, and shower before using swimming pools or whirlpools.
In September 2004, the UK National Health Service announced its Clean Your Hands campaign. It was recommended that alcohol-based hand rubs be placed near beds to encourage staff to use the sanitizer more regularly. It was thought that even if this cuts infection by no more than 1%, the plan will pay for itself many times over.
Excluding medical facilities, current US guidance does not require workers with MRSA infections to be routinely excluded from the general workplace. The National Institutes of Health recommends that those with wound drainage that cannot be covered and contained with a clean, dry bandage and those who cannot maintain good hygiene practices be reassigned. Workers with active infections are excluded from activities where skin-to-skin contact is likely to occur. To prevent the spread of staph or MRSA in the workplace, employers make available adequate facilities that encourage good hygiene. In addition, surface and equipment sanitizing conforms to the Environmental Protection Agency (EPA)-registered disinfectants. Health Departments recommend that preventing the spread of MRSA in the home can be to: launder materials that have come into contact with infected person separately and with a dilute bleach solution; reduce the bacterial load in your nose and on your skin; clean those things in the house that people regularly touch like sinks, tubs, kitchen counters, cell phones, light switches, doorknobs, phones, toilets, and computer keyboards.
Restricting antibiotic use
Glycopeptides, cephalosporins, and, in particular, quinolones are associated with an increased risk of colonisation of MRSA. Reducing use of antibiotic classes that promote MRSA colonisation, especially fluoroquinolones, is recommended in current guidelines.
Public health considerations
Mathematical models describe one way in which a loss of infection control can occur after measures for screening and isolation seem to be effective for years, as happened in the UK. In the "search and destroy" strategy that was employed by all UK hospitals until the mid-1990s, all hospitalized people with MRSA were immediately isolated, and all staff were screened for MRSA and were prevented from working until they had completed a course of eradication therapy that was proven to work. Loss of control occurs because colonised people are discharged back into the community and then readmitted; when the number of colonised people in the community reaches a certain threshold, the "search and destroy" strategy is overwhelmed. One of the few countries not to have been overwhelmed by MRSA is the Netherlands: An important part of the success of the Dutch strategy may have been to attempt eradication of carriage upon discharge from hospital.
The Centers for Disease Control and Prevention (CDC) estimated that about 1.7 million nosocomial infections occurred in the United States in 2002, with 99,000 associated deaths. The estimated incidence is 4.5 nosocomial infections per 100 admissions, with direct costs (at 2004 prices) ranging from $10,500 (£5300, €8000 at 2006 rates) per case (for bloodstream, urinary tract, or respiratory infections in immunocompetent people) to $111,000 (£57,000, €85,000) per case for antibiotic-resistant infections in the bloodstream in people with transplants. With these numbers, conservative estimates of the total direct costs of nosocomial infections are above $17 billion. The reduction of such infections forms an important component of efforts to improve healthcare safety. (BMJ 2007) MRSA alone was associated with 8% of nosocomial infections reported to the CDC National Healthcare Safety Network from January 2006 to October 2007.
This problem is not unique to one country; the British National Audit Office estimated that the incidence of nosocomial infections in Europe ranges from 4% to 10% of all hospital admissions. 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 3,000 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.
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 three U.S. communities 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 people required hospitalization.
As of 2013 there had been no randomized clinical trials conducted to understand how to treat non-surgical wounds that had been colonized, but not infected, with MRSA, and insufficient studies had been conducted to understand how to treat surgical wounds that had been colonized with MRSA. As of 2013 it was not known whether strategies to eradicate MRSA colonization of people in nursing homes reduced infection rates.
Care should be taken when trying to drain boils, as disruption of surrounding tissue can lead to larger infections, or even infection of the blood stream (often with fatal consequences).
Mupirocin (Bactroban) 2% ointment can be effective at reducing the size of lesions. A secondary covering of clothing is preferred. As shown in an animal study with diabetic mice, the topical application of a mixture of sugar (70%) and 3% povidone-iodine paste is an effective agent for the treatment of diabetic ulcers with MRSA infection.
In the hospital setting toilet seats are a common vector for infection, and wiping seats clean before and/or after use can help to prevent the spread of MRSA. Door handles, faucets, light switches, etc. can be disinfected regularly with disinfectant wipes. Spray disinfectants can be used on upholstery. Carpets can be washed with disinfectant, and hardwood floors can be scrubbed with diluted tea tree oil (e.g. Melaleuca). Laundry soap containing tea tree oil may be effective at decontaminating clothing and bedding, especially if hot water and heavy soil cycles are used, however tea tree oil may cause a rash which MRSA can re-colonize. Alcohol-based sanitizers can be placed near bedsides, near sitting areas, in vehicles etc. to encourage their use.
It may be difficult for people to maintain the necessary cleanliness if they do not have access to facilities such as public toilets with handwashing facilities. In the United Kingdom, the Workplace (Health, Safety and Welfare) Regulations 1992 requires businesses to provide toilets for their employees, along with washing facilities including soap or other suitable means of cleaning. Guidance on how many toilets to provide and what sort of washing facilities should be provided alongside them is given in the Workplace (Health, Safety and Welfare) Approved Code of Practice and Guidance L24, available from Health and Safety Executive Books. But there is no legal obligation on local authorities in the United Kingdom to provide public toilets, and although in 2008 the House of Commons Communities and Local Government Committee called for a duty on local authorities to develop a public toilet strategy this was rejected by the Government.
Treatment is urgent and delays can be fatal.:328 The location and history related to the infection determines the treatment. The route of administration of an antibiotic varies. Antibiotics effective against MRSA can be given by IV, oral, or a combination of both and depends on the specific circumstances and patient characteristics. The use of concurrent treatment with vancomycin other beta-lactam agents may have a synergistic effect.:637
Both CA-MRSA and HA-MRSA are resistant to traditional anti-staphylococcal beta-lactam antibiotics, such as cephalexin. CA-MRSA has a greater spectrum of antimicrobial susceptibility to sulfa drugs (like co-trimoxazole (trimethoprim/sulfamethoxazole), tetracyclines (like doxycycline and minocycline) and clindamycin (for osteomyelitis). MRSA can be eradicated with a regimen of linezolid, though treatment protocols vary and serum levels of antibiotics vary widely person to person and may affect outcomes. The effective treatment of MRSA with linezolid has been successful in 87% of people. Linezolid is more effective in soft tissue infections than vancomycin. This is compared to eradication of infection in those with MRSA treated with vancomycin. Treatment with vancomycin is successful in approximately 49% of people. Linezolid and daptomycin belong to the newer oxazolidinones which has been shown to be effective against both CA-MRSA and HA-MRSA. The Infectious Disease Society of America recommends vancomycin, linezolid, or clindamycin (if susceptible) for treating those with MRSA pneumonia. Ceftaroline, a fifth-generation cephalosporin, is the first beta-lactam antibiotic approved in the US to treat MRSA infections in skin and soft tissue or community acquired pneumonia.
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. Because the oral absorption of vancomycin and teicoplanin is very low, these agents can be administered intravenously to control systemic infections. Treatment of MRSA infection with vancomycin can be complicated, due to its inconvenient route of administration. Moreover, the efficacy of vancomycin against MRSA is inferior to that of anti-staphylococcal beta-lactam antibiotics against methicillin-susceptible Staphylococcus aureus (MSSA).
Several newly discovered strains of MRSA show antibiotic resistance even to vancomycin and teicoplanin. These new strains of the MRSA bacterium have been dubbed vancomycin intermediate-resistant Staphylococcus aureus (VISA).  Linezolid, quinupristin/dalfopristin, daptomycin, ceftaroline, and tigecycline are used to treat more severe infections that do not respond to glycopeptides such as vancomycin. Current guidelines recommend daptomycin for VISA bloodstream infections and endocarditis.
Skin and soft-tissue infections
In skin abscesses, the primary treatment recommended is removal of dead tissue, incision and drainage. More data is needed to determine the effectiveness of specific antibiotics therapy in SSIs. Examples of soft tissue infections from MRSA include: ulcers, impetigo, abscesses, and surgical site infections.
In skin infections and in secondary infection sites topical mupirocin is used successfully. For bacteremia and endocarditis, vancomycin or daptomycin is considered. For children with MRSA infected bone or joints, treatment is individualized and long-term. Neonates can develop Neonatal pustulosis as a result of topical infection with MRSA. Clindamycin is not approved for the treatment of MRSA infection it is still used in children for soft tissue infections.
Endocarditis and bacteremia
Evaluation for the replacement of a prosthetic valve is considered. Appropriate antibiotic therapy may be administered for up to six weeks. Four to six weeks of antibiotic treatment is often recommended, and is dependent upon the extent of MRSA infection.
CA-MRSA in hospitalized patients pneumonia treatment begins before culture results. After the susceptibility to antibiotics is performed, the infection may be treated with vancomycin or linezolid for up to 21 days. If the pneumonia is complicated by the accumulation of pus in the pleural cavity surrounding the lungs, drainage may be done along with antibiotic therapy. People with cystic fibrosis may develop respiratory complications related to MRSA infection. The incidence of MRSA in those with cystic fibrosis increased during 200 to 2015 by five times. Most of these infections were HA-MRSA. MRSA accounts for 26% of lung infections in those with cystic fibrosis.
Bone and joint infections
Cleaning the wound of dead tissue and draining abscesses is the first action to treat the MRSA infection. Administration of antibiotics is not standardized and is adapted by a case-by-case basis. Antibiotic therapy can last up to 1 to 3 months and sometimes even longer.
MRSA infection can occur associated with implants and joint replacements. Recommendations on treatment are based upon the length of time the implant has been in place. In cases of a recent placement of a surgical implant or artificial joint, the device may be retained while antibiotic therapy continues. If the placement of the device has occurred over 3 weeks ago, the device may be removed. Antibiotic therapy is used in each instance sometimes long-term.
Central nervous system
MRSA can infect the central nervous system and form brain abscess, subdural empyema, and spinal epidural abscess. Excision and drainage can be done along with antibiotic treatment. Septic thrombosis of cavernous or dural venous sinus can sometimes be a complication.
Treatment is not standardized for other instances of MRSA infection in a wide range of tissues. Treatment varies for MRSA infections related to: subperiosteal abscesses, necrotizing pneumonia, cellulitis, pyomyositis, necrotizing fasciitis, mediastinitis, myocardial, perinephric, hepatic, and splenic abscesses, septic thrombophlebitis, and severe ocular infections, including endophthalmitis. Pets can be reservoirs and pass on MRSA to people. In some cases, the infection can be symptomatic and the pet can suffer a MRSA infection. Health departments recommend that the pet be taken to the veterinarian if MRSA infections keep occurring in the people who have contact with the pet.
In a US cohort study of 1300 healthy children, 2.4% carried MRSA in their nose. Bacterial sepsis occurs with most (75%) of cases of invasive MRSA infection. In 2009, there were an estimated 463,017 hospitalization due to MRSA or a rate of 11.74 per 1,000 hospitalizations. Many of these infections are less serious, but the Centers for Disease Control and Prevention (CDC) estimates that there are 80,461 invasive MRSA infections and 11,285 deaths due to MRSA annually. In 2003, the cost for a hospitalization due to a MRSA was $92,363, A hospital stay for MSSA was $52,791 (USD).
Infection after surgery is relatively uncommon, but occurs as much as 33% in specific types of surgeries. Infections of surgical sites range from 1% to 33%. MRSA sepsis that occurs within 30 days has a 15-38% mortality rate. MRSA sepsis that occurs within one year following a surgical infection has a mortality rate of around 55%. There may be increased mortality associated with cardiac surgery. There is of rate of 12.9% in those infected with MRSA while only a 3% infected with other organisms. SSIs infected with MRSA had longer hospital stays than those who did not.
Globally, MRSA infection rates are dynamic and vary year to year. According to The 2006 SENTRY Antimicrobial Surveillance Program report, the incidence of MRSA blood stream infections was 35.9 per cent in North America. MRSA blood infections in Latin America was 29%. European incidence was 22.8%. The rate of all MRSA infections in Europe ranged from 50% per cent in Portugal down to 0.8 per cent in Sweden. Overall MRSA infection rates varied in Latin America: Colombia and Venezuela combined had 3%, Mexico had 50%, Chile 38%, Brazil 29%, and Argentina 28%.
In a US cohort study of 1300 healthy children, 2.4% carried MRSA in their nose.
There are concerns that the presence of MRSA in the environment may allow resistance to be transferred to other bacteria through phages (viruses that infect bacteria). The source of MRSA could come from hospital waste, farm sewage, and other waste water.
Livestock associated MRSA (LA-MRSA) has been observed in Korea, Brazil, Switzerland, Malaysia, India, Great Britain, Denmark, and China.
A 1,000-year-old eye salve recipe found in the medieval Bald's Leechbook at the British Library, one of the earliest known medical textbooks, was found to have activity against MRSA in vitro and in skin wounds in mice.
MRSA was first discovered in 1961 In 1959 - 1961. In 1961, Methicillin was licensed in England to treat penicillin-resistant S. aureus infections. In 1961 the first known MRSA isolates were reported in a British study, and from 1961 to 1967 there were infrequent hospital outbreaks in Western Europe and Australia. Other reports of MRSA began to be described in the 1970s. Resistance to other antibiotics was documented in some strains of S. aureus. In 1996, vancomycin resistance was reported in Japan.:637 In many countries, outbreaks of MRSA infection was reported to be transmitted between hospitals.:402 The rate had increased to 22% by 1995, and by 1997 the percent of hospital S. aureus infections attributable to MRSA had reached 50%.
The first report of community-associated MRSA (CA-MRSA) occurred in 1981, and in 1982 there was a large outbreak of CA-MRSA among intravenous drug users in Detroit, Michigan. Additional outbreaks of CA-MRSA were reported through the 1980s and 1990s, including outbreaks among Australian Aboriginal populations that had never been exposed to hospitals. In the mid-1990s there were scattered reports of CA-MRSA outbreaks among US children. While HA-MRSA rates stabilized between 1998 and 2008, CA-MRSA rates continued to rise. A report released by the University of Chicago Children's Hospital comparing two time periods (1993–1995 and 1995–1997) found a 25-fold increase in the rate of hospitalizations due to MRSA among children in the United States. In 1999 the University of Chicago reported the first deaths from invasive MRSA among otherwise healthy children in the United States. By 2004, the genome for various strains of MRSA were described.
It has been argued that the observed increased mortality among MRSA-infected people may be the result of the increased underlying morbidity of these people. Several studies, however, including one by Blot and colleagues, that have adjusted for underlying disease still found MRSA bacteremia to have a higher attributable mortality than methicillin-susceptible S. aureus (MSSA) bacteremia.
A population-based study of the incidence of MRSA infections in San Francisco during 2004–05 demonstrated that nearly 1 in 300 residents suffered from such an infection in the course of a year and that greater than 85% of these infections occurred outside of the healthcare setting. A 2004 study showed that people in the United States with S. aureus infection had, on average, three times the length of hospital stay (14.3 vs. 4.5 days), incurred three times the total cost ($48,824 vs. $14,141), and experienced five times the risk of in-hospital death (11.2% vs 2.3%) than people without this infection. In a meta-analysis of 31 studies, Cosgrove et al., concluded that MRSA bacteremia is associated with increased mortality as compared with MSSA bacteremia (odds ratio= 1.93; 95% CI = 1.93 ± 0.39). In addition, Wyllie et al. report a death rate of 34% within 30 days among people infected with MRSA, a rate similar to the death rate of 27% seen among MSSA-infected people.
In the US, the Centers for Disease Control and Prevention issued guidelines on October 19, 2006, citing the need for additional research, but declined to recommend such screening.
According to the CDC, the most recent estimates of the incidence of healthcare-associated infections that are attributable to MRSA in the United States indicate a decline in such infection rates. Incidence of MRSA central line-associated blood stream infections as reported by hundreds of intensive care units decreased 50–70% from 2001–2007. A separate system tracking all hospital MRSA bloodstream infections found an overall 34% decrease between 2005–2008.
In 2010, vancomycin was the drug of choice.
Across Europe, based mostly on data from 2013 seven countries (Iceland, Norway, Sweden, Netherlands, Denmark, Finland, and Estonia, from lowest to higher) had low levels of hospital-acquired MRSA infections compared to the others,:92–93 and among countries with higher levels significant improvements had been made only in Bulgaria, Poland and the British Isles.:40
- The herbs daphne genkwa and Olresin both have shown to have constitiuents in them that when combined with traditional antibiotics elicit a strong response against MRSA infections.
- Various antibacterial chemical extracts from various species of the Sweetgum tree, (genus Liquidambar) have been investigated for their activity in inhibiting MRSA. Specifically these are: cinnamic acid, cinnamyl cinnamate, ethyl cinnamate, benzyl cinnamate, styrene, vanillin, cinnamyl alcohol, 2-phenylpropyl alcohol, 3-phenylpropyl cinnamate, and vanillin.
- The delivery of inhaled antibiotics along with systematic administration to treat MRSA are being developed. It's believed that this will improve the outcomes of those with cystic fibrosis and other respiratory infections.
|Wikimedia Commons has media related to MRSA.|
A colourised SEM of MRSA
In popular culture
MRSA is frequently a media topic, especially if well-known personalities have announced that they have or have had the infection. Outbreaks of infection appear regularly in newspapers and television news programs. A report on skin and soft tissue infections in the Cook County jail in Chicago in 2004–05 demonstrated MRSA was the most common cause of these infections among those incarcerated there. Lawsuits that are filed against those who are accused of infecting others with MRSA are also popular stories in the media. MRSA will be included in experiments and cultured on the International Space Station to observe the effects of zero gravity on its evolution.
- Gurusamy, Kurinchi Selvan; Koti, Rahul; Toon, Clare D.; Wilson, Peter; Davidson, Brian R. (2013-08-20). "Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds". The Cochrane Database of Systematic Reviews (8): CD009726. ISSN 1469-493X. PMID 23963687. doi:10.1002/14651858.CD009726.pub2.
- Murray, Patrick (2007). Manual of clinical microbiology. Washington, D.C: ASM Press. ISBN 9781555813710.
- Winn, Washington (2006). Koneman's color atlas and textbook of diagnostic microbiology. Philadelphia: Lippincott Williams & Wilkins. ISBN 0781730147.
- Schenck, LP; Surette, MG; Bowdish, DM (November 2016). "Composition and immunological significance of the upper respiratory tract microbiota.". FEBS Letters. 590 (21): 3705–3720. PMID 27730630. doi:10.1002/1873-3468.12455.
- Wollina, U (2017). "Microbiome in atopic dermatitis.". Clinical, cosmetic and investigational dermatology. 10: 51–56. PMC . PMID 28260936. doi:10.2147/CCID.S130013.
- Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; Rybak, Michael J.; Talan, David A.; Chambers, Henry F. (2011). "Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children". Clinical Infectious Diseases. 52 (3): e18–e55. ISSN 1058-4838. PMID 21208910. doi:10.1093/cid/ciq146.
- Sganga, G.; Tascini, C.; Sozio, E.; Carlini, M.; Chirletti, P.; Cortese, F.; Gattuso, R.; Granone, P.; Pempinello, C.; Sartelli, M.; Colizza, S. (2016). "Focus on the prophylaxis, epidemiology and therapy of methicillin-resistant Staphylococcus aureus surgical site infections and a position paper on associated risk factors: the perspective of an Italian group of surgeons". World Journal of Emergency Surgery. 11 (1). ISSN 1749-7922. PMC . PMID 27307786. doi:10.1186/s13017-016-0086-1.
- "General Information About MRSA in the Community". Centers for Disease Control and Prevention. 10 September 2013. Retrieved 9 October 2014.
- Lipsky BA, Tabak YP, Johannes RS, Vo L, Hyde L, Weigelt JA (May 2010). "Skin and soft tissue infections in hospitalised patients with diabetes: culture isolates and risk factors associated with mortality, length of stay and cost". Diabetologia. 53 (5): 914–23. PMID 20146051. doi:10.1007/s00125-010-1672-5.
- Otter, J.A.; French, G.L. "Community-associated meticillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection". Journal of Hospital Infection. 79 (3): 189–193. doi:10.1016/j.jhin.2011.04.028.
- Golding, George R.; Quinn, Brian; Bergstrom, Kirsten; Stockdale, Donna; Woods, Shirley; Nsungu, Mandiangu; Brooke, Barb; Levett, Paul N.; Horsman, Greg; McDonald, Ryan; Szklarczuk, Brian; Silcox, Steve; Paton, Shirley; Carson, Mary; Mulvey, Michael R.; Irvine, James. "Community-based educational intervention to limit the dissemination of community-associated methicillin-resistant Staphylococcus aureus in Northern Saskatchewan, Canada". BMC Public Health. 12 (1): 15. PMC . PMID 22225643. doi:10.1186/1471-2458-12-15.
- Tacconelli E, De Angelis G, Cataldo MA, Pozzi E, Cauda R (Jan 2008). "Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis". J Antimicrob Chemother. 61 (1): 26–38. PMID 17986491. doi:10.1093/jac/dkm416.
- Dumyati, G; Stone, ND; Nace, DA; Crnich, CJ; Jump, RL (April 2017). "Challenges and Strategies for Prevention of Multidrug-Resistant Organism Transmission in Nursing Homes.". Current infectious disease reports. 19 (4): 18. PMC . PMID 28382547. doi:10.1007/s11908-017-0576-7.
- Reuters (2009-02-16). "Study: Beachgoers More Likely to Catch MRSA". FoxNews.com.
- Marilynn Marchione (2009-09-12). "Dangerous staph germs found at West Coast beaches". Associated Press.
- Zinderman CE, Conner B, Malakooti MA, LaMar JE, Armstrong A, Bohnker BK (May 2004). "Community-Acquired Methicillin-Resistant Staphylococcus aureus Among Military Recruits". Emerging Infectious Diseases. 10 (5): 941–4. PMC . PMID 15200838. doi:10.3201/eid1005.030604.
- "MRSA History Timeline: The First Half-Century, 1959-2009". The University of Chicago Medical Center. 2010.
- David MZ, Daum RS (2010). "Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic" (PDF). Clinical Microbiology Reviews. American Society for Microbiology. 23 (6): 616–687. PMC . PMID 20610826. doi:10.1128/CMR.00081-09.
- Gopal, S; Divya, KC (March 2017). "Can methicillin-resistant Staphylococcus aureus prevalence from dairy cows in India act as potential risk for community-associated infections?: A review.". Veterinary world. 10 (3): 311–318. PMC . PMID 28435193. doi:10.14202/vetworld.2017.311-318.
- Ficalora, Robert (2013). Mayo Clinic internal medicine board review. Oxford: Oxford University Press. ISBN 9780199948949.
- Gurusamy, KS; Koti, R; Toon, CD; Wilson, P; Davidson, BR (18 November 2013). "Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds.". The Cochrane database of systematic reviews (11): CD010427. PMID 24242704. doi:10.1002/14651858.CD010427.pub2.
- Jacobs, A (2014). "Hospital-acquired methicillin-resistant Staphylococcus aureus: status and trends.". Radiologic technology. 85 (6): 623–48; quiz 649–52. PMID 25002642.
- Muto CA, Jernigan JA, Ostrowsky BE, Richet HM, Jarvis WR, Boyce JM, Farr BM (May 2003). "SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus". Infect Control Hosp Epidemiol. 24 (5): 362–86. PMID 12785411. doi:10.1086/502213.
- Hughes, C; Tunney, M; Bradley, MC (19 November 2013). "Infection control strategies for preventing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes for older people.". The Cochrane database of systematic reviews (11): CD006354. PMID 24254890. doi:10.1002/14651858.CD006354.pub4.
- "PURE Bioscience". purebio.com.
- Singh, Jatinder; Johnson, Ryan C.; Schlett, Carey D.; Elassal, Emad M.; Crawford, Katrina B.; Mor, Deepika; Lanier, Jeffrey B.; Law, Natasha N.; Walters, William A. (2016-10-26). "Multi-Body-Site Microbiome and Culture Profiling of Military Trainees Suffering from Skin and Soft Tissue Infections at Fort Benning, Georgia". mSphere. 1 (5): e00232–16. ISSN 2379-5042. PMC . PMID 27747300. doi:10.1128/mSphere.00232-16.
- Mehndiratta, P. L., & Bhalla, P. (2014). "Use of Antibiotics in Animal Agriculture & Emergence of Methicillin Resistant Staphylococcus Aureus (MRSA) Clones: Need to Assess the Impact on Public Health". Indian J Med Res. 140: 339–44. PMC . PMID 25366200.
- Vitale, Carlo; Gross, T.; Weese, J. "Methicillin-resistantStaphylococcus aureus in Cat and Owner". Emerging Infectious Diseases. 12 (12): 1998–2000. PMC . PMID 17354344. doi:10.3201/eid1212.060725. This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention.
- Salgado, Cassandra D.; Farr, Barry M.; Calfee, David P. (15 January 2003). "Community‐Acquired Methicillin‐Resistant Staphylococcus aureus: A Meta‐Analysis of Prevalence and Risk Factors". Clinical Infectious Diseases. 36 (2): 131–139. doi:10.1086/345436.
- Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B, Boo T, McAllister S, Anderson J, Jensen B, Dodson D, Lonsway D, McDougal LK, Arduino M, Fraser VJ, Killgore G, Tenover FC, Cody S, Jernigan DB (2005-02-03). "A clone of methicillin-resistant Staphylococcus aureus among professional football players". The New England Journal of Medicine. 352 (5): 468–75. PMID 15689585. doi:10.1056/NEJMoa042859.
- Epstein, Victor (21 December 2007). "Texas Football Succumbs to Virulent Staph Infection From Turf". Bloomberg. Retrieved 10 June 2010.
- Yasinskas, Pat (11 October 2013). "Third Tampa Bay Buccaneers player tests positive for MRSA staph infection". ESPN. ESPN Internet Ventures. Retrieved 11 October 2013.
- Hernandez, Dylan (August 12, 2015). "Dodgers' Justin Turner nears return from MRSA infection". Los Angeles Times. Retrieved August 13, 2015.
- Rappoport, Ian (October 11, 2015). "MRSA infection leaves Giants' Daniel Fells in dire situation". NFL.com. Retrieved October 12, 2015.
- Gray JW (April 2004). "MRSA: the problem reaches paediatrics". Arch. Dis. Child. 89 (4): 297–8. PMC . PMID 15033832. doi:10.1136/adc.2003.045534.
- Bratu S, Eramo A, Kopec R, Coughlin E, Ghitan M, Yost R, Chapnick EK, Landman D, Quale J (June 2005). "Community-associated methicillin-resistant Staphylococcus aureus in hospital nursery and maternity units". Emerging Infect. Dis. 11 (6): 808–13. PMC . PMID 15963273. doi:10.3201/eid1106.040885.
- Association for Professionals in Infection Control & Epidemiology (June 25, 2007). "National Prevalence Study of Methicillin-Resistant Staphylococcus aureus (MRSA) in U.S. Healthcare Facilities". Archived from the original on September 7, 2007. Retrieved 2007-07-14.
- "Staph Infections and MRSA in Children: Prevention, Symptoms, and Treatment". webmd.com.
- Francois P, Schrenzel J (2008). "Rapid Diagnosis and Typing of Staphylococcus aureus". Staphylococcus: Molecular Genetics. Caister Academic Press. ISBN 978-1-904455-29-5.
- Mackay IM, ed. (2007). Real-Time PCR in Microbiology: From Diagnosis to Characterization. Caister Academic Press. ISBN 978-1-904455-18-9.
- Seiken, Denka. "MRSA latex test for PBP2".
- Jensen SO, Lyon BR (June 2009). "Genetics of antimicrobial resistance in Staphylococcus aureus". Future Microbiol. 4 (5): 565–82. PMID 19492967. doi:10.2217/fmb.09.30.
- Lowy FD (May 2003). "Antimicrobial resistance: the example of Staphylococcus aureus". J. Clin. Invest. 111 (9): 1265–73. PMC . PMID 12727914. doi:10.1172/JCI18535.
- Pantosti A, Sanchini A, Monaco M (June 2007). "Mechanisms of antibiotic resistance in Staphylococcus aureus". Future Microbiol. 2 (3): 323–34. PMID 17661706. doi:10.2217/174609184.108.40.2063.
- Kaito C, Saito Y, Nagano G, Ikuo M, Omae Y, Hanada Y, Han X, Kuwahara-Arai K, Hishinuma T, Baba T, Ito T, Hiramatsu K, Sekimizu K (2011). Cheung A, ed. "Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence". PLoS Pathog. 7 (2): e1001267. PMC . PMID 21304931. doi:10.1371/journal.ppat.1001267.
- Cheung, Gordon Y. C.; Villaruz, Amer E.; Joo, Hwang-Soo; Duong, Anthony C.; Yeh, Anthony J.; Nguyen, Thuan H.; Sturdevant, Daniel E.; Queck, S. Y.; Otto, M. (2014-07-01). "Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus". International journal of medical microbiology: IJMM. 304 (5–6): 637–644. ISSN 1618-0607. PMC . PMID 24877726. doi:10.1016/j.ijmm.2014.04.008.
- Enright, M.C.; Robinson, D.A. (2002). "The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA).". PNAS. 99: 7687–92. PMC . PMID 12032344. doi:10.1073/pnas.122108599.
- Wu, S.W.; de Lencastre, H. (2001). "Recruitment of the mecA gene homolog of Staphyoloccus sciuri into a resistance determinant and expression of the resistance phenotype in Staphylococcus aureus". Journal of Bacteriology. 183.
- Kuo SC, Chiang MC, Lee WS, Chen LY, Wu HS, Yu KW, Fung CP, Wang FD (January 2012). "Comparison of microbiological and clinical characteristics based on SCCmec typing in patients with community-onset meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia". Int. J. Antimicrob. Agents. 39 (1): 22–6. PMID 21982834. doi:10.1016/j.ijantimicag.2011.08.014.
- Collins, J.; Rudkin, J. (2010). "Offsetting virulence and antibiotic resistance costs by MRSA". International Society for Microbial Ecology. 4.
- Sahebnasagh R, Saderi H, Owlia P. Detection of methicillin-resistant Staphylococcus aureus strains from clinical samples in Tehran by detection of the mecA and nuc genes. The First Iranian International Congress of Medical Bacteriology; 4–7 September; Tabriz, Iran. 2011. 195 pp.
- Berger-Bächi B (November 1999). "Genetic basis of methicillin resistance in Staphylococcus aureus". Cell. Mol. Life Sci. 56 (9–10): 764–70. PMID 11212336. doi:10.1007/s000180050023.
- Goering RV, McDougal LK, Fosheim GE, Bonnstetter KK, Wolter DJ, Tenover FC (2007). "Epidemiologic distribution of the arginine catabolic mobile element among selected methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates". J. Clin. Microbiol. 45 (6): 1981–4. PMC . PMID 17409207. doi:10.1128/JCM.00273-07.
- Gordon RJ, Lowy FD (June 2008). "Pathogenesis of methicillin-resistant Staphylococcus aureus infection". Clin. Infect. Dis. 46 (Suppl 5): S350–9. PMC . PMID 18462090. doi:10.1086/533591.
- Johnson AP, Aucken HM, Cavendish S, Ganner M, Wale MC, Warner M, Livermore DM, Cookson BD (2001). "Dominance of EMRSA-15 and -16 among MRSA causing nosocomial bacteraemia in the UK: analysis of isolates from the European Antimicrobial Resistance Surveillance System (EARSS)". J Antimicrob Chemother. 48 (1): 143–4. PMID 11418528. doi:10.1093/jac/48.1.143.
- Diep BA, Carleton HA, Chang RF, Sensabaugh GF, Perdreau-Remington F (2006). "Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus". J Infect Dis. 193 (11): 1495–503. PMID 16652276. doi:10.1086/503777.
- Stefani S, Chung DR, Lindsay JA, Friedrich AW, Kearns AM, Westh H, Mackenzie FM (2012). "Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods". International Journal of Antimicrobial Agents. 39 (4): 273–82. ISSN 0924-8579. PMID 22230333. doi:10.1016/j.ijantimicag.2011.09.030.
- Calfee DP (2011). "The epidemiology, treatment, and prevention of transmission of methicillin-resistant Staphylococcus aureus". J Infus Nurs. 34 (6): 359–64. PMID 22101629. doi:10.1097/NAN.0b013e31823061d6.
- Daum RS (2007). "Skin and Soft-Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus". New England Journal of Medicine. 357 (4): 380–390. PMID 17652653. doi:10.1056/NEJMcp070747.
- Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, Kennedy AD, Dorward DW, Klebanoff SJ, Peschel A, DeLeo FR, Otto M (December 2007). "Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA". Nat. Med. 13 (12): 1510–4. PMID 17994102. doi:10.1038/nm1656.
- Tristan A, Bes M, Meugnier H, Lina G, Bozdogan B, Courvalin P, Reverdy ME, Enright MC, Vandenesch F, Etienne J (2007). "Global distribution of Panton–Valentine leukocidin--positive methicillin-resistant Staphylococcus aureus, 2006". Emerging Infect. Dis. 13 (4): 594–600. PMC . PMID 17553275. doi:10.3201/eid1304.061316.
- Gould IM, David MZ, Esposito S, Garau J, Lina G, Mazzei T, Peters G (February 2012). "New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance". Int. J. Antimicrob. Agents. 39 (2): 96–104. PMID 22196394. doi:10.1016/j.ijantimicag.2011.09.028.
- David MZ, Rudolph KM, Hennessy TW, Boyle-Vavra S, Daum RS (2008). "Molecular epidemiology of methicillin-resistant Staphylococcus aureus, rural southwestern Alaska". Emerging Infect. Dis. 14 (11): 1693–9. PMC . PMID 18976551. doi:10.3201/eid1411.080381.
- Panel on Biological Hazards (16 June 2009). "Joint scientific report of ECDC, EFSA and EMEA on meticillin resistant Staphylococcus aureus (MRSA) in livestock, companion animals and food.". EFSA Journal. doi:10.2903/j.efsa.2009.301r.
- Graveland H, Duim B, van Duijkeren E, Heederik D, Wagenaar JA (December 2011). "Livestock-associated methicillin-resistant Staphylococcus aureus in animals and humans". Int. J. Med. Microbiol. 301 (8): 630–4. PMID 21983338. doi:10.1016/j.ijmm.2011.09.004.
- Tacconelli E, De Angelis G, de Waure C, Cataldo MA, La Torre G, Cauda R (September 2009). "Rapid screening tests for meticillin-resistant Staphylococcus aureus at hospital admission: systematic review and meta-analysis". Lancet Infect Dis. 9 (9): 546–54. PMID 19695491. doi:10.1016/S1473-3099(09)70150-1.
- McCaughey B. "Unnecessary Deaths: The Human and Financial Costs of Hospital Infections" (PDF) (2nd ed.). Archived from the original (PDF) on July 11, 2007. Retrieved 2007-08-05.
- "Personal Prevention of MRSA Skin Infections". CDC. 9 August 2010. Retrieved 25 May 2017. This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention.
- "NPSA - About us".
- "NIOSH MRSA and the Workplace". United States National Institute for Occupational Safety and Health. Retrieved 2017-05-25.
- CDC (1998). "Guidelines for Infection Control in Health Care Personnel, 1998". Centers for Disease Control and Prevention. Retrieved December 18, 2007.
- "Living With MRSA" (PDF). Group Health Cooperative/Tacoma-Pierce County Health Dept./Washington State Dept. of Health. Retrieved 20 November 2011.
- Cooper BS, Medley GF, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Duckworth G, Lai R, Ebrahim S (2004). "Methicillin-resistant Staphylococcus aureus in hospitals and the community: stealth dynamics and control catastrophes". Proc Natl Acad Sci USA. 101 (27): 10223–8. PMC . PMID 15220470. doi:10.1073/pnas.0401324101.
- Bootsma MC, Diekmann O, Bonten MJ (2006). "Controlling methicillin-resistant Staphylococcus aureus: quantifying the effects of interventions and rapid diagnostic testing". Proc Natl Acad Sci USA. 103 (14): 5620–5. PMC . PMID 16565219. doi:10.1073/pnas.0510077103.
- Klevens RM, Edwards JR, Richards CL, Horan TC, Gaynes RP, Pollock DA, Cardo DM (2007). "Estimating health care-associated infections and deaths in U.S. hospitals, 2002". Public Health Rep. 122 (2): 160–6. PMC . PMID 17357358.
- Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK (November 2008). "NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007". Infect Control Hosp Epidemiol. 29 (11): 996–1011. PMID 18947320. doi:10.1086/591861.
- Johnson AP, Pearson A, Duckworth G (2005). "Surveillance and epidemiology of MRSA bacteraemia in the UK". J Antimicrob Chemother. 56 (3): 455–62. PMID 16046464. doi:10.1093/jac/dki266.
- "MRSA Infections". Keep Kids Healthy.
- Graham PL, Lin SX, Larson EL (2006). "A U.S. population-based survey of Staphylococcus aureus colonization". Annals of Internal Medicine. 144 (5): 318–25. PMID 16520472. doi:10.7326/0003-4819-144-5-200603070-00006.
- Jernigan JA, Arnold K, Heilpern K, Kainer M, Woods C, Hughes JM (2006-05-12). "Methicillin-resistant Staphylococcus aureus as community pathogen". Symposium on Community-Associated Methicillin-resistant Staphylococcus aureus (Atlanta, Georgia, U.S.). Cited in Emerg Infect Dis. Centers for Disease Control and Prevention. Retrieved 2007-01-27.
- "PubMed Health". US National Institutes of Health. Retrieved 20 November 2011.
- Shi CM, Nakao H, Yamazaki M, Tsuboi R, Ogawa H (November 2007). "Mixture of sugar and povidone-iodine stimulates healing of MRSA-infected skin ulcers on db/db mice". Arch. Dermatol. Res. 299 (9): 449–56. PMID 17680256. doi:10.1007/s00403-007-0776-3.
- Foundation, Internet Memory. "[ARCHIVED CONTENT] UK Government Web Archive – The National Archives". Archived from the original on 2012-09-19.
- "Government Response to the Communities and Local Government Committee Report on the Provision of Public Toilets". Archived from the original on 2012-09-19.
- Gurusamy, Kurinchi Selvan; Wilson, Peter; Davidson, Brian R; Gurusamy, Kurinchi Selvan (2013). "Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD010427.
- Choo, Eun Ju; Chambers, Henry F. (2016). "Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia". Infection & Chemotherapy. 48 (4): 267. ISSN 2093-2340. doi:10.3947/ic.2016.48.4.267.
- Yue, Jirong; Dong, Bi Rong; Yang, Ming; Chen, Xiaomei; Wu, Taixiang; Liu, Guan J; Dong, Bi Rong (2016). "Linezolid versus vancomycin for skin and soft tissue infections". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD008056.pub3.
- "FDA Approves Teflaro for Bacterial Infections".
- Schentag JJ, Hyatt JM, Carr JR, Paladino JA, Birmingham MC, Zimmer GS, Cumbo TJ (1998). "Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control". Clin. Infect. Dis. 26 (5): 1204–14. PMID 9597254. doi:10.1086/520287.
- Rybak MJ, Lerner SA, Levine DP, Albrecht LM, McNeil PL, Thompson GA, Kenny MT, Yuh L (1991). "Teicoplanin pharmacokinetics in intravenous drug abusers being treated for bacterial endocarditis". Antimicrob. Agents Chemother. 35 (4): 696–700. PMC . PMID 1829880. doi:10.1128/AAC.35.4.696.
- Janknegt R (1997). "The treatment of staphylococcal infections with special reference to pharmacokinetic, pharmacodynamic, and pharmacoeconomic considerations". Pharmacy world & science: PWS. 19 (3): 133–41. PMID 9259029. doi:10.1023/A:1008609718457.
- Chang FY, Peacock JE, Musher DM, Triplett P, MacDonald BB, Mylotte JM, O'Donnell A, Wagener MM, Yu VL (2003). "Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study". Medicine (Baltimore). 82 (5): 333–9. PMID 14530782. doi:10.1097/01.md.0000091184.93122.09.
- Siegman-Igra Y, Reich P, Orni-Wasserlauf R, Schwartz D, Giladi M (2005). "The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia". Scand J Infect Dis. 37 (8): 572–8. PMID 16138425. doi:10.1080/00365540510038488.
- Sieradzki K, Tomasz A (1997). "Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus". J. Bacteriol. 179 (8): 2557–66. PMC . PMID 9098053.
- Schito GC (2006). "The importance of the development of antibiotic resistance in Staphylococcus aureus". Clin Microbiol Infect. 12 (Suppl 1): 3–8. PMID 16445718. doi:10.1111/j.1469-0691.2006.01343.x.
- Mongkolrattanothai K, Boyle S, Kahana MD, Daum RS (2003). "Severe Staphylococcus aureus infections caused by clonally related community-associated methicillin-susceptible and methicillin-resistant isolates". Clin. Infect. Dis. 37 (8): 1050–8. PMID 14523769. doi:10.1086/378277.
- Maselli, Diego; Keyt, Holly; Restrepo, Marcos (2017). "Inhaled Antibiotic Therapy in Chronic Respiratory Diseases (Review)". International Journal of Molecular Sciences. 18 (5): 1062. ISSN 1422-0067. doi:10.3390/ijms18051062.
- Fritz SA, Garbutt J, Elward A, Shannon W, Storch GA (2008). "Prevalence of and risk factors for community-acquired methicillin-resistant and methicillin-sensitive Staphylococcus aureus colonization in children seen in a practice-based research network". Pediatrics. 121 (6): 1090–8. PMID 18519477. doi:10.1542/peds.2007-2104.
- Eili Y. Klein; Lova Sun; David L. Smith; Ramanan Laxminarayan (2013). "The Changing Epidemiology of Methicillin-Resistant Staphylococcus aureus in the United States: A National Observational Study". American Journal of Epidemiology. 177 (7): 666–674. doi:10.1093/aje/kws273.
- "Antibiotic Resistance Threats in the United States, 2013 - Antibiotic/Antimicrobial Resistance - CDC". This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention.
- "ResistanceMap - Antibiotic Resistance". resistancemap.cddep.org. Center for Disease Dynamics, Economics & Policy. 2017. Retrieved 27 May 2017. note: a search must be performed on the website; it is interactive and the statistics are based upon the most current information,
- Thompson, Nick; Smith-Spark, Laura. "Thousand-year-old Anglo-Saxon potion kills MRSA superbug". CNN News. CNN/Time Warner. Retrieved 1 April 2015.
- "Community-acquired MRSA in Children with no predisposing risk" (PDF).
- Holden MT, Feil EJ, Lindsay JA, Peacock SJ, Day NP, Enright MC, Foster TJ, Moore CE, Hurst L, Atkin R, Barron A, Bason N, Bentley SD, Chillingworth C, Chillingworth T, Churcher C, Clark L, Corton C, Cronin A, Doggett J, Dowd L, Feltwell T, Hance Z, Harris B, Hauser H, Holroyd S, Jagels K, James KD, Lennard N, Line A, Mayes R, Moule S, Mungall K, Ormond D, Quail MA, Rabbinowitsch E, Rutherford K, Sanders M, Sharp S, Simmonds M, Stevens K, Whitehead S, Barrell BG, Spratt BG, Parkhill J (2004). "Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance". Proc Natl Acad Sci USA. 101 (26): 9786–91. PMC . PMID 15213324. doi:10.1073/pnas.0402521101.
- Blot SI, Vandewoude KH, Hoste EA, Colardyn FA (2002). "Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus". Arch Intern Med. 162 (19): 2229–35. PMID 12390067. doi:10.1001/archinte.162.19.2229.
- Liu C, Graber CJ, Karr M, Diep BA, Basuino L, Schwartz BS, Enright MC, O'Hanlon SJ, Thomas JC, Perdreau-Remington F, Gordon S, Gunthorpe H, Jacobs R, Jensen P, Leoung G, Rumack JS, Chambers HF (June 2008). "A population-based study of the incidence and molecular epidemiology of methicillin-resistant Staphylococcus aureus disease in San Francisco, 2004–2005". Clin. Infect. Dis. 46 (11): 1637–46. PMID 18433335. doi:10.1086/587893.
- Noskin GA, Rubin RJ, Schentag JJ, Kluytmans J, Hedblom EC, Smulders M, Lapetina E, Gemmen E (2005). "The Burden of Staphylococcus aureus Infections on Hospitals in the United States: An Analysis of the 2000 and 2001 Nationwide Inpatient Sample Database". Arch Intern Med. 165 (15): 1756–1761. PMID 16087824. doi:10.1001/archinte.165.15.1756.
- Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y (2005). "The impact of Methicillin Resistance in Staphylococcus aureus Bacteremia on Patient Outcomes: Mortality, Length of Stay, and Hospital Charges". Infection Control and Hospital Epidemiology. 26 (2): 166–174. PMID 15756888. doi:10.1086/502522.
- Hardy KJ, Hawkey PM, Gao F, Oppenheim BA (2004). "Methicillin resistant Staphylococcus aureus in the critically ill". British Journal of Anaesthesia. 92 (1): 121–30. PMID 14665563. doi:10.1093/bja/aeh008.
- Wyllie DH, Crook DW, Peto TE (2006). "Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 1997–2003: cohort study". BMJ. 333 (7562): 281. PMC . PMID 16798756. doi:10.1136/bmj.38834.421713.2F.
- "Healthcare-associated infections - HAI - CDC" (PDF). cdc.gov.
- "MRSA Surveillance". Centers for Disease Control and Prevention. April 8, 2011.
- "Outcomes in EHCI 2015" (PDF). Health Consumer Powerhouse. 26 January 2016. Retrieved 27 January 2016.
- Kuok, Chiu-Fai; Hoi, Sai-On; Hoi, Chi-Fai; Chan, Chi-Hong; Fong, Io-Hong; Ngok, Cheong-Kei; Meng, Li-Rong; Fong, Pedro (2017-04-01). "Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study". Experimental Biology and Medicine (Maywood, N.J.). 242 (7): 731–743. ISSN 1535-3699. PMC . PMID 28118725. doi:10.1177/1535370216689828.
- Crandall, PhilipG; Lingbeck, JodyM; O′Bryan, CorlissA; Martin, ElizabethM; Adams, JoshuaP (2015). "Sweetgum: An ancient source of beneficial compounds with modern benefits". Pharmacognosy Reviews. 9 (17): 1. ISSN 0973-7847. doi:10.4103/0973-7847.156307.
- "Bucs' Nicks, Tynes have MRSA infections". Tampa Bay Times. Retrieved 3 June 2017.
- Correspondent, Elizabeth Cohen, Senior Medical. "MRSA: The tiny bacteria that can tackle giants". CNN. Retrieved 3 June 2017.
- Cush, Sam Biddle and Andy. "This Australian Says He and His Dead Friend Invented Bitcoin". Retrieved 3 June 2017.
- "Hospital Infection Lawsuits are on the Rise - AboutLawsuits.com". www.aboutlawsuits.com. Retrieved 3 June 2017.
- "Doc who treated superbug vic was sued before". Retrieved 3 June 2017.
- "The Next SpaceX Launch Will Carry Deadly Bacteria". 7 February 2017. Retrieved 3 June 2017.
- "KDC Projects". www.kdcprojects.com. Retrieved 3 June 2017.
- "MRSA: The Drug-Resistant 'Superbug' That Won't Die". NPR.org. Retrieved 3 June 2017.
- ""Should I Worry About...?" MRSA (TV Episode 2004)". Retrieved 3 June 2017.
- McKenna, Maryn. "Resistance: The Movie That Will Make You Care About Antibiotic Misuse". Retrieved 3 June 2017.
- "Line of Duty series 4: Everything you need to know". 24 April 2017. Retrieved 3 June 2017.
- "Facing the Future of Antibiotic Resistance - The Change Starts Here". HuffPost UK. Retrieved 3 June 2017.
- The Centers for Disease Control and Prevention information, prevention, statistics, at risk groups, causes, educational resources, and environmental factors.
- National Institute for Occupational Safety and Health information on the bacteria, exposure in the workplace, and reducing risks of being infected.
- Medline research, information, treatments, and causes.
- Maryn McKenna (2011). Superbug: The Fatal Menace of MRSA. Free Press. ISBN 978-1-4165-5728-9.
- Karch, Amy (2017). Focus on nursing pharmacology. Philadelphia: Wolters Kluwer. ISBN 9781496318213.
- Lois Reynolds; Tilli Tansey, eds. (2008), Wellcome Witnesses to Contemporary Medicine, History of Modern Biomedicine Research Group, ISBN 978-0-85484-114-1 http://www.histmodbiomed.org/witsem/vol32 Missing or empty
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- Vallerand, April (2017). Davis's drug guide for nurses. Philadelphia: F.A. Davis Company. ISBN 9780803657052.