Methicillin-resistant Staphylococcus aureus


Methicillin-resistant Staphylococcus aureus is a group of gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths worldwide attributable to antimicrobial resistance in 2019.
MRSA is any strain of S. aureus that has developed or acquired a multiple drug resistance to beta-lactam antibiotics. Beta-lactam antibiotics are a broad-spectrum group that include some penams and cephems such as the cephalosporins. Strains unable to resist these antibiotics are classified as methicillin-susceptible S. aureus, or MSSA.
MRSA infection is common 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 healthcare-associated infection. MRSA began as a hospital-acquired infection but has become community-acquired, as well as livestock-acquired. The terms HA-MRSA, CA-MRSA, and LA-MRSA reflect this.

Signs and symptoms

In humans, Staphylococcus aureus is part of the normal microbiota present in the upper respiratory tract, and on skin and in the gut mucosa. However, along with similar bacterial species that can colonize and act symbiotically, they can cause disease if they begin to take over the tissues they have colonized or invade other tissues; the resultant infection has been called a "pathobiont".
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.

Risk factors

A select few of the populations at risk include:
  • 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
  • Diabetics
  • Intravenous drug users
  • Regular contact with someone who has injected drugs in the past year
  • Users of quinolone antibiotics
  • Elderly people
  • 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
  • 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, and military recruits in basic training
  • Veterinarians, livestock handlers, and pet owners
  • People who ingest unpasteurized milk
  • People who are immunocompromised and also colonized
  • People with chronic obstructive pulmonary disease
  • People who have had thoracic surgery
As many as 22% of people colonised with MRSA do not have any discernible risk factors.

Hospitalized people

People who are hospitalized, including the elderly, are often immunocompromised and susceptible to infection of all kinds, including MRSA; an infection by MRSA is called healthcare-associated or hospital-acquired methicillin-resistant S. aureus.
Generally, those infected by MRSA stay infected for just under 10 days, if treated by a doctor, although effects may vary from person to person.
Both surgical and nonsurgical wounds can be infected with HA-MRSA. Surgical site infections occur on the skin surface, but can spread to internal organs and blood to cause sepsis. Transmission can occur between healthcare providers and patients because some providers may neglect to perform preventative hand-washing between examinations.
People in nursing homes are at risk for all the reasons above, further complicated by their generally weaker immune systems.

Prison inmates and military personnel

Prisons and military barracks can be crowded and confined, and poor hygiene conditions 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 later in Canada. The earliest reports were made by the Centers for Disease Control and Prevention 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.

Animals

increases the risk that MRSA will develop among the livestock and other animals that may reside near them; strains MRSA ST398 and CC398 are transmissible to humans. Generally, animals are asymptomatic.
Domestic pets are susceptible to MRSA infection by transmission from their owners; conversely, MRSA-infected pets can also transmit MRSA to humans.

Athletes

, 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 and 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 whether Banks contracted it from either individual is unknown. 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.

Children

MRSA is becoming a critical problem in children; studies found 4.6% of patients in U.S. health-care facilities, including hospital nurseries, were infected or colonized with MRSA. Children and adults 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 contracting MRSA. Parents should be especially cautious of children who participate in activities where sports equipment is shared, such as football helmets and uniforms.

Intravenous drug users

Needle-required drugs have caused an increase of MRSA, with injection drug use making up 24.1% of Tennessee Hospital's Discharge System. The unsanitary methods of injection cause an access point for the MRSA to enter the bloodstream and begin infecting the host. Furthermore, with MRSA's high contagion rate, a common risk factor is individuals who are in constant contact with someone who has injected drugs in the past year.

Mechanism

is genetically based; resistance is mediated by the acquisition of extrachromosomal genetic elements containing genes that confer resistance to certain antibiotics. Examples of such elements include plasmids, transposable genetic elements, and genomic islands, which can be 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 the synthesis of cell wall material. This is due to a resistance gene, mecA, which stops β-lactam antibiotics from inactivating the enzymes critical for cell wall synthesis.

SCC''mec''

Staphylococcal cassette chromosome mec 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 RNAs known as 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 to 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 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 the carriage of a large or small SCCmec plasmid. Carriage of large plasmids, such as SCCmecI–III, is costly to the bacteria, resulting in a compensatory decrease in virulence expression. MRSA can 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.