MRSA (methicillin-resistant Staphylococcus aureus) is a type of staph bacteria that is resistant to several antibiotics. Historically, staph strains that are oxacillin and methicillin-resistant are termed MRSA. MRSA is resistant to all ß-lactam agents, including cephalosporins and carbapenems.
In the community, MRSA is primarily responsible for causing skin infections. It can also cause pneumonia, soft tissue infections, and if left untreated can cause sepsis. In healthcare settings such as hospitals, MRSA can cause severe problems such as bloodstream infections, pneumonia, and surgical site infections.
Timeline of development of resistance in Staphylococcus aureus
- 1800s: Discovery/first report about Staphylococcus aureus.
- 1940-1950s: Use of Penicillin to treat S. aureus infections.
- 1944: First reported case of penicillin-resistant S. aureus (some literature claims that penicillin-resistant strains of S. aureus had been detected in hospitals in 1942s).
- 1959: Introduction of Methicillin to treat penicillin-resistant S. aureus
- In 1961: British scientists reported the
firstcase of Methicillin-Resistant Staphylococcus aureus.
- In 1968: The first reported human case of Methicillin-Resistant Staphylococcus aureus in the United States
- In 2002: First documented case of vancomycin resistance S. aureus (VRSA) in the
Development of Methicillin Resistance
Methicillin resistance is mediated by PBP-2a, an alternative penicillin-binding protein encoded by the mecA gene, which permits the organism to grow and divide in the presence of methicillin and other beta-lactam antibiotics. The mecA gene is part of a 21- to 60-kb staphylococcal chromosome cassette
Scientists believed that MRSA strains have evolved a number of times by means of horizontal transfer of mecA among methicillin-suspectiable S. aureus (MSSA) precursor strains with the resulting formation of numerous MRSA clones. There are 6 SCCmec subtypes (types I–VI), which vary in size from ∼20 kb to 68 kb. A single clone probably accounted for most MRSA isolates recovered during the 1960s; by 2004, so far six major clones have emerged worldwide.
Types: CA-MRSA Vs. HA-MRSA
Until the detection of MRSA in
The majority of staph and MRSA infections occur in hospitals or other health care settings in patients with weakened immune systems. Infections in a patient that occurs after 48 hours of hospitalization
In contrast, a CA-MRSA infection is defined as an infection that occurs in a patient who has been in the hospital for less than 48 hours; in other words, they probably carried the infection in with them. CA-MRSA is an infection occurring in people who have not been hospitalized/haven’t had a medical procedure in the past year and are otherwise healthy. Most CA-MRSA strains frequently carry SCCmec type IV or V; in addition, they carry genes for the cytotoxin Panton-Valentine leukocidin (PVL) that confers enhanced virulence (this is now a debatable issue as some researchers have questioned the importance of PVL as a determinant of virulence in CA-MRSA). Most CA-MRSA strains are sensitive to non-beta-lactam antibiotics, although a multidrug-resistant isolate has been described.
Detection of Oxacillin/Methicillin Resistance
Earlier, methicillin disk diffusion test was used to detect methicillin resistance in S.aureus which was later replaced by oxacillin as oxacillin maintains its activity during storage better than methicillin and is more likely to detect heteroresistant strains. Now, cefoxitin is recommended as a surrogate for disk diffusion testing because it is a better inducer of the mecA gene. Tests using cefoxitin give more reproducible and accurate results than tests with oxacillin.
Clinical and Laboratory Standards Institute (CLSI) recommends broth microdilution testing for MRSA. Alternative recommended methods include cefoxitin disk screen test, the latex agglutination test for PBP2a, or a plate containing 6 μg/ml of oxacillin in Mueller-Hinton agar supplemented with 4% NaCl. The CLSI breakpoints for S. aureus are as follows:
Oxacillin MIC Tests|
Cefoxitin MIC Tests|
Cefoxitin Disk Diffusion Test |
|Sensitive||≤ 2 μg/ml||≤ 4 μg/ml||≥ 22 mm|
|Resistant||≥ 4 μg/ml||≥ 8 μg/ml||≤ 21 mm|
Nucleic acid amplification tests (NAATs), such as the polymerase chain reaction (PCR), can be used to detect the mecA gene. However, mecA PCR tests will not detect novel resistance mechanisms such as mecC or uncommon phenotypes such as borderline-resistant oxacillin resistance.