Methicillin-resistant Staphylococcus aureus

From Wikipedia, the free encyclopedia "MRSA" redirects here. For other uses, see MRSA (disambiguation).

Methicillin-resistant Staphylococcus aureus

Scanning electron micrograph of a human neutrophil ingesting MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for several difficult-to-treat infections in humans. It is also called oxacillin-resistant Staphylococcus aureus (ORSA). MRSA is any strain of Staphylococcus aureus that has developed, through the process of natural selection, resistance to beta-lactam antibiotics, which include the penicillins (methicillin, dicloxacillin, nafcillin, oxacillin, etc.) and the cephalosporins. Strains unable to resist these antibiotics are classified as methicillin-sensitive Staphylococcus aureus, or MSSA. The evolution of such resistance does not cause the organism to be more intrinsically virulent than strains of Staphylococcus aureus that have no antibiotic resistance, but resistance does make MRSA infection more difficult to treat with standard types of antibiotics and thus more dangerous. MRSA is especially troublesome in hospitals, prisons and nursing homes, where patients with open wounds, invasive devices, and weakened immune systems are at greater risk of infection than the general public.

Signs and symptoms

S. aureus most commonly colonizes the anterior nares (the nostrils).[1] The rest of the respiratory tract, open wounds, intravenous catheters, and the urinary tract are also potential sites for infection. Healthy individuals may carry MRSA asymptomatically for periods ranging from a few weeks to many years. Patients with compromised immune systems are at a significantly greater risk of symptomatic secondary infection. In most patients, MRSA can be detected by swabbing the nostrils and isolating the bacteria found inside. Combined with extra sanitary measures for those in contact with infected patients, screening patients admitted to hospitals has been found to be effective in minimizing the spread of MRSA in hospitals in the United States,[2] Denmark, Finland, and the Netherlands.[3] MRSA may progress substantially within 2448 hours of initial topical symptoms. 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.[4] About 75 percent of community-associated (CA-) MRSA infections are localized to skin and soft tissue and usually can be treated effectively.[5] But some CA-MRSA strains display enhanced virulence, spreading more rapidly and causing illness much more severe than traditional healthcare-associated (HA-) MRSA infections, and they can affect vital organs and lead to widespread infection (sepsis), toxic shock syndrome, and necrotizing ("flesh-eating") pneumonia. This is thought to be due to toxins carried by CA-MRSA strains, such as PVL and PSM, though PVL was recently found not to be a factor in a study by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health. (NIH) It is not known why some healthy people develop CA-MRSA skin infections that are treatable while others infected with the same strain develop severe infections or die.[6] People are very commonly colonized with CA-MRSA and are completely asymptomatic. The most common manifestations of CA-MRSA are simple skin infections, such as impetigo, boils, abscesses, folliculitis, and cellulitis. Rarer, but more serious manifestations can occur, such as necrotizing fasciitis and pyomyositis (most commonly found in the tropics), necrotizing pneumonia, infective endocarditis (which affects the valves of the heart), and bone and joint infections.[7] CA-MRSA often results in abscess formation that requires incision and drainage. Before the spread of MRSA into the community, abscesses were not considered contagious, because it was assumed that infection required violation of skin integrity and the introduction of staphylococci from normal skin colonization. However, newly emerging CA-MRSA is transmissible (similar, but with very important differences) from Hospital-Associated MRSA. CA-MRSA is less likely than other forms of MRSA to cause cellulitis.

Risk factors
Some of the populations at risk:

People with weak immune systems (HIV/AIDS, lupus, or cancer sufferers; transplant recipients, severe asthmatics, etc.) Diabetics[8] Intravenous drug users [9] Users of quinolone antibiotics[10] Young children[citation needed] The elderly[citation needed] College students living in dormitories[9] For woman with frequent UTI's or kidney infections due to infections in the bladder People staying or working in a health care facility for an extended period of time[9] 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[11][12] People who spend time in confined spaces with other people, including occupants of homeless shelters and warming centers, prison inmates, military recruits in basic training,[13] and individuals who spend considerable time in changerooms or gyms.[citation
needed]

Veterinarians, livestock handlers, and pet owners[14]

Hospital patients
Many MRSA infections occur in hospitals and healthcare facilities. When infections occur in this manner it is known as healthcare acquired MRSA or HA-MRSA. These Rates of MRSA infection are also increased in hospitalized patients who are treated with quinolones. Healthcare provider-to-patient transfer is common, especially when healthcare providers move from patient to patient without performing necessary hand-washing techniques between patients.[10][15]

Prison inmates, military recruits, and the homeless

Prisons, military barracks, and homeless shelters can be crowded and confined, and poor hygiene practices may proliferate, thus putting inhabitants at increased risk of contracting MRSA.[14] 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. Subsequently reports of a massive rise in skin and soft tissue infections were reported by the CDC in the Los Angeles County Jail system in 2001, and this has continued. Pan et al. reported on the changing epidemiology of MRSA skin infection in the San Francisco County Jail, noting MRSA accounted for more than 70% of S. aureus infection in the jail by 2002. Lowy and colleagues reported on frequent MRSA skin infections in New York State Prisons. Two reports on inmates in Maryland have demonstrated frequent colonization with MRSA. 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 the U.S. State of Oklahoma started treating an average of twelve Staphylococcus cases per month.[16] A report on skin and soft tissue infections in the Cook County Jail in Chicago in 200405 demonstrated that MRSA was the most common cause of these infections among cultured lesions and furthermore that 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.

People in contact with live food-producing animals

Cases of MRSA have increased in livestock animals. CC398 is a new variant of MRSA that has emerged in animals and is found in intensively reared production animals (primarily pigs, but also cattle and poultry), where it can be transmitted to humans. Though dangerous to humans, CC398 is often asymptomatic in food-producing animals.[17] A 2011 study reported 47% of the meat and poultry sold in surveyed U.S. grocery stores was contaminated with S. aureus and, of those, 52%or 24.4% of the totalwere resistant to at least three classes of antibiotics. "Now we need to determine what this means in terms of risk to the consumer," said Dr. Keim, a co-author of the paper.[18] Some samples of commercially sold meat products in Japan were also found to harbor MRSA strains.[19]

Athletes

In the United States, there have been increasing numbers of reports of outbreaks of MRSA colonization and infection through skin contact in locker rooms and gyms, even among healthy populations.[citation needed] A study published in the New England Journal of Medicine linked MRSA to the abrasions caused by artificial turf.[20] Three studies by the Texas State Department of Health found that 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.[21] In 2013, Lawrence Tynes, Carl Nicks, and Johnthan Banks of the Tampa Bay Buccaneers were diagnosed with MRSA. It is believed that Tynes and Nicks did not contract the infection from each other, but it is unknown if Banks contracted it from either individual.[22]

Children
MRSA is becoming a critical problem in pediatric settings;[23] recent studies found that 4.6% of patients in U.S. health care facilities, (presumably) including hospital nurseries,[24] were infected or colonized with MRSA.[25] Children are more susceptible to MRSA because they are more likely to exhibit minor scrapes, cuts, bruises, and bug bites than adults. 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 there is shared sports equipment such as football helmets and uniforms.[26]

Diagnosis
Mueller Hinton agar showing MRSA resistant to oxacillin disk Diagnostic microbiology laboratories and reference laboratories are key for identifying outbreaks of MRSA. Faster techniques for identifying and characterizing MRSA have recently been developed.[27] 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 there is no quick and easy method 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.[28][29] 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.[30]

Genetics

Antimicrobial resistance is genetically based; resistance is mediated by the acquisition of extrachromosomal genetic elements containing resistance genes. Exemplary are plasmids, transposable genetic elements, and genomic islands, which are transferred between bacteria via horizontal gene transfer.[31] 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 -lactam antibiotics from inactivating the enzymes (transpeptidases) that are critical for cell wall synthesis.

SCCmec
Staphylococcal cassette chromosome mec (SCCmec) is a genomic island of unknown origin containing the antibiotic resistance gene mecA.[32][33] SCCmec contains additional genes beyond mecA, including the cytolysin gene psm-mec, which may suppress virulence in hospital-acquired MRSA strains.[34] 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.[32][33] Currently, six unique SCCmec types ranging in size from 2167 kb have been identified;[32] they are designated types I-VI and are distinguished by variation in mec and ccr gene complexes.[31] Owing to the size of the SCCmec element and the constraints of horizontal gene transfer, a limited number of clones is thought to be responsible for the spread of MRSA infections.[32] Different SCCmec genotypes confer different microbiological characteristics, such as different antimicrobial resistance rates.[35] 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.[33][35] Conversely, CA-MRSA is associated with types IV and V, which are smaller and lack resistance genes other than mecA.[33][35]

mecA
mecA is responsible for resistance to methicillin and other -lactam antibiotics. After acquisition of mecA, the gene must be integrated and localized in the S. aureus chromosome.[32] mecA encodes penicillin-binding protein 2a (PBP2a), which differs from other penicillin-binding proteins as its active site does not bind methicillin or other -lactam antibiotics.[32] As such, PBP2a can continue to catalyze the transpeptidation reaction required for peptidoglycan crosslinking, enabling cell wall synthesis in the presence of antibiotics. As a consequence of the inability of PBP2a to interact with -lactam moieties, acquisition of mecA confers resistance to all -lactam antibiotics in addition to methicillin.[32][36] 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.[31][33] In the presence of a -lactam antibiotic, MecR1 initiates a signal transduction cascade that leads to transcriptional activation of mecA.[31][33] This is achieved by MecR1-mediated cleavage of MecI, which alleviates MecI repression.[31] 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.[32][37] The DNA sequences bound by MecI and BlaI are identical;[32] therefore, BlaI can also bind the mecA operator to repress transcription of mecA.[37]