Methicillin Resistant Staphylococcus Aureus (MRSA)

Bacteria become antimicrobial resistant by acquiring a gene that permits inactivation of a particular antibiotic or class of antibiotics. It is estimated that more than 70% of bacteria that cause hospital-acquired infections are resistant to at least one commonly used antibiotic. 

Staphylococcus aureus was the first known bacteria to acquire antibiotic resistance; penicillin was introduced in 1941 and resistance appeared in 1944. Today, methicillin-resistant Staphylococcus aureus (MRSA) is often associated with hospital or nursing home acquired infections. Interestingly, genetic studies have revealed that acquisition of the methicillin-resistance gene (mec) by MRSA has occurred only a few times. Therefore, the MRSA common to many hospitals has resulted from dissemination of only a few clones. Transmission of those MRSA clones between cities, countries, and continents has been traced to the transfer of patients infected or colonized with MRSA. Risk factors associated with hospital-acquired MRSA infections include prolonged hospitalization, care in an intensive care unit, prolonged antibiotic therapy, surgical procedures and close proximity to another patient who is infected or colonized with MRSA. In U.S. hospitals, nearly 50% of all Staphylococcus aureus isolates are methicillin resistant. In the hospital setting, MRSA can be associated with severe infections including sepsis, osteomyelitis, wound and surgical infections, and endocarditis.

MRSA infections also occur in people with little or no contact with healthcare facilities and no other risk factors. This type of MRSA is referred to as community-acquired MRSA (CA-MRSA). CA-MRSA has emerged as a distinctly different infectious agent than MRSA that causes health-care associated infections (HA-MRSA). CA-MRSA is predominantly associated with skin and soft tissue infections in otherwise healthy children and young adults. Outbreaks have been documented among sports teams and correctional facility inmates. Fatal pulmonary infections in children have also been reported. CA-MRSA is typically resistant only to B-lactam antibiotics and erythromycin, while HA-MRSA is usually resistant to multiple antibiotics.

The molecular characteristics of CA-MRSA have been published. Hundreds of CA-MRSA organisms have been analyzed by pulsed-field gel electrophoresis (PFGE). PFGE is a strain typing method that is used to determine how closely related 2 or more bacterial isolates are to each other. This technique has revealed that most CA-MRSA strains within the U.S. belong to just two clones, designated USA 300 and USA 400. The latter is associated with severe pneumonia in children and skin infections in Native American populations. USA 300 accounts for the majority of the remaining CA-MRSA skin and soft tissue infections, and has now been identified in several outbreaks ranging geographically from Washington State to Florida.     

Staphylococcus aureus is known to produce multiple toxins which contribute to its virulence. A toxin known as Panton-Valentine leucocidin (PVL) has been identified in the majority of CA-MRSA isolates, but not in HA-MRSA. PVL genes encode membrane toxins which target leukocytes, and are epidemiologically linked to severe skin infections and necrotizing pneumonia. Another molecular characteristic of CA-MRSA is its resistance gene, designated SCCmec type IV, that is distinct from the mec A resistance gene harbored by HA-MRSA.  

In summary, CA-MRSA organisms are distinct clones, and not hospital-associated organisms that have moved into the general public. The prevalence of CA-MRSA is rapidly increasing. Clinicians should have a high index of suspicion for CA-MRSA, particularly when a wound resembling a “spider-bite” is present. Culture and susceptibility testing should be requested.  

A study of MRSA prevalence in skin and soft tissue infections in emergency department (ED) patients was undertaken during the month of August 2004 It included ED’s in 11 U.S. cities from New York to Los Angeles. Enrollment included 422 adult ED patients that had infections classified as abscesses (81%), wound infections (11%) and purulent cellulitis (8%). Cultures were performed on all patients with susceptibility testing performed on all isolates of S. aureus. 

MRSA was found to be the most common identifiable cause of skin and soft tissue infection in 10 of the 11 ED’s in the study. The prevalence of MRSA in 10 of the ED’s ranged from 39% (Minneapolis) to 74% (Kansas City), and averaged 59% overall. The only ED in which methicillin-sensitive S. aureus was more prevalent than MRSA was in New York (40% vs. 15%). The majority of the MRSA strains from the study were sent to the CDC for typing and 99% were found to be consistent with previously characterized CA-MRSA. The most common identifiable risk factors for MRSA infection included presence of an abscess, reported spider bite, close contact of someone with a similar infection, and use of any antibiotic within the past month. Spontaneous infections, defined as no apparent precipitating factor, were also commonly reported. Susceptibility testing of the MRSA isolates revealed that 100% were susceptible to trimethoprim-sulfamethoxazole, 95% to clindamycin, 92% to tetracycline, and 60% to quinolones. Eighty percent of the patients received empirical antibiotic therapy, but only 43% were infected with a strain susceptible to the chosen antibiotic. 

References

Moran GJ et al, Methicillin-Resistant S. Aureus Infections among Patients in the Emergency Department, New Engl J Med, 2006;355(7):666-674.

Herold, BC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998;279:593-598.

Lakhundi S, Zhang K. Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology. Clin Microbiol Rev. 2018;31(4):e00020-18.