Shortly after the introduction of methicillin in 1959, isolates resistant to this agent were reported. Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infections occurred in Europe in the early 1960s. Since these original descriptions, MRSA as well as coagulase-negative staphylococci, which are commonly resistant to methicillin, have emerged as major nosocomial and, in the case of MRSA, community-acquired pathogens.
Methicillin resistance is defined in the clinical microbiology laboratory as an oxacillin minimum inhibitory concentration ≥4 mcg/mL. Isolates resistant to oxacillin or methicillin are also resistant to all beta-lactam agents, including cephalosporins.
Methicillin resistance requires the presence of the mec gene; strains lacking a mec gene are not methicillin resistant. The structural component of the mec gene, mecA, encodes the penicillin-binding protein 2a (PBP2a) that establishes resistance to methicillin and other semisynthetic penicillinase resistant beta-lactams.
The most accurate methods to detect MRSA are polymerase chain reaction for detection of the mecA gene and latex agglutination tests for the protein product of mecA, PBP2a. When these tests are not available, traditional microbiology laboratory techniques are acceptable, such as oxacillin-salt agar screening plates and cefoxitin disk diffusion tests. Rapid testing for detection of MRSA is discussed in detail separately.
Methicillin is a semisynthetic beta-lactamase–resistant penicillin that was introduced in 1959; shortly thereafter, isolates of Staphylococcus aureus and coagulase-negative staphylococci with methicillin resistance were described. Outbreaks of methicillin-resistant S. aureus (MRSA) infection occurred in Europe in the early 1960s. Subsequently, these organisms have emerged as major nosocomial and community-acquired pathogens.
Three pandemic MRSA clones have been traced back to the original 1959 MRSA isolates in Denmark and England. In addition, molecular typing of MRSA strains collected from many geographic areas has revealed that five major MRSA clones emerged worldwide by 2002. The epidemic community-associated MRSA strains in the early 2000s appear to have emerged from earlier epidemic clones.
Our understanding of the genetic mechanisms responsible for methicillin resistance will be reviewed here. Virulence determinants for community-acquired MRSA are discussed separately, as are mechanisms for S. aureus with reduced susceptibility to vancomycin.
Methicillin resistance requires the presence of the mec gene; strains lacking a mec gene are not methicillin resistant. Methicillin resistance is defined in the clinical microbiology laboratory as an oxacillin minimum inhibitory concentration (MIC) ≥4 mcg/mL. Other methods of detection, such as the use of the cefoxitin disk diffusion test or one of several polymerase chain reactions to detect the mec gene, are also used. Isolates resistant to oxacillin or methicillin are also resistant to all beta-lactam agents, including cephalosporins (with the exception of ceftaroline, a fifth-generation cephalosporin). MICs of ≤2 mcg/mL are considered susceptible.
Prevention and control
Basic infection prevention principles include attention to careful hand hygiene and adherence to contact precautions for care of patients with known MRSA infection.
Active surveillance cultures identify asymptomatic individuals with MRSA colonization to be placed on contact precautions with the goal of minimizing MRSA spread to other patients. This practice is appropriate in the setting of an outbreak; its role for routine screening is a question of ongoing debate.
We suggest that decolonization not be performed in the routine management of MRSA infections (Grade 2B). Decolonization does not appear to be consistently effective for eliminating MRSA carriage, and emergence of resistance to agents used for decolonization will limit the utility of such protocols.
We suggest performing decolonization in the setting of a MRSA outbreak, particularly if there is epidemiologic evidence pointing to transmission by one or more healthcare workers or among individuals in a specific population (Grade 2C). Regimens are outlined above.
Additional important components for MRSA prevention and control include environmental cleaning and prudent antibiotic use.
Tools for preventing MRSA spread in the community include hand hygiene and minimizing risk factors for transmission. Decolonization may be appropriate if there is epidemiologic evidence pointing to transmission within a household.
The optimal role for active surveillance is not known, and there is insufficient evidence for a single routine approach. Active surveillance cultures appear to be most useful in the setting of hospital outbreaks and among patients at high risk for MRSA carriage. Such patients include:
- Patients with history of MRSA colonization (such patients should be isolated initially pending surveillance testing results)
- Patients in intensive care units (ICUs)
- Patients who are immunocompromised
- Residents of long-term care facilities
- Patients on hemodialysis
- Patients hospitalized in the previous 12 months
- Patients who have received antibiotic therapy in the last three months
- Patients with skin or soft tissue infection at admission
Advocates of active surveillance have pointed to its success among several European countries where MRSA has been contained at a low prevalence (examples include the Netherlands, Finland, and France). These strategies involved a multifaceted approach including surveillance, contact isolation, healthcare worker screening with decolonization, and closing units for comprehensive screening and cleaning when warranted. Given this combination of interventions, it is not certain which intervention or combination of interventions is required for MRSA control. Therefore, extrapolating these experiences to other healthcare settings with variable MRSA prevalence and other factors may be difficult.
Institutions performing surveillance cultures should establish clear policies regarding how the results will be used to make decisions about contact precautions, cohorting, and decolonization. Educational programming about adherence is imperative for patients, visitors, healthcare workers, environmental cleaners, and other hospital personnel.