MRSA: Emergence, Types, and Detection Methods

This post was most recently updated on February 9th, 2019

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 as MRSA. MRSA are 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 tissues infections and if left untreated can cause sepsis.
In health-care 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

Resistance in S.aureus
Timeline of Resistance Development in S. aureus
(Thanks to my friend Maniss Trilli Microvilli for making this image.)
  1. 1800s: Discovery/first report about Staphylococcus aureus.
  2. 1940-1950s: Use of Penicillin to treat S. aureus infections.
  3. 1944: First reported case of penicillin-resistant S. aureus (some literature claims that penicillin resistance strains of S. aureus had been detected in hospitals in 1942s).
  4. 1959: Introduction of Methicillin to treat penicillin-resistant S. aureus
  5. In 1961: British scientists reported first case of
    Methicillin-Resistant Staphylococcus aureus.
  6. In 1968: The first reported human case of Methicillin-Resistant Staphylococcus aureus in the United States
  7. In 2002: First documented case of vancomycin resistance S. aureus (VRSA) in United States


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 mec (SCCmec), a mobile genetic element that may also contain genetic structures such as Tn554 (Tn554 encodes resistance to macrolides, clindamycin, and streptogramin B), pUB110, and pT181 (pT181 encodes resistance to tetracyclines) which encode resistance to non-β-lactam antibiotics.

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 1990s from US patients, who have never been hospitalized, MRSA was thought as a pathogen associated with nosocomial infections. Currently, we believe that there are two separate strains of MRSA; health care—associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) which differs with respect to their clinical and molecular epidemologies but the line between them is significantly blurred.

HA-MRSA
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 is known as HA-MRSA. Risk factors of HA-MRSA infection include antibiotic use, prolonged hospitalization, intensive care, hemodialysis, MRSA colonization, and proximity to individuals with MRSA colonization or infection. HA-MRSA strains tend to have multidrug resistance and carry SCCmec type I-III, mostly SCCme type II.

CA-MRSA
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 theimportance 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 even 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 includes 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
(in μg/ml)
Cefoxitin MIC Tests
(in μg/ml)
Cefoxitin Disk Diffusion Test
(in mm)
Sensitive ≤ 2 μg/ml ≤ 4 μg/ml ≥ 22 mm
Intermediate NA NA NA
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.

References and further readings:

About tankeshwar 386 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion, I am working as an Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.

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