MRSA and Vancomycin-Resistant Staphylococci
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Direct answer
Methicillin-resistant Staphylococcus aureus (MRSA) carries the mecA gene, which encodes penicillin-binding protein 2a, an enzyme with low affinity for beta-lactam antibiotics. Resistance extends to nearly all beta-lactams, including oxacillin and cloxacillin, so the organism is managed as resistant to the whole class. Vancomycin-intermediate and vancomycin-resistant strains are much rarer, but each one changes treatment and must be reported.
What you must remember
- mecA gene: carried on the staphylococcal cassette chromosome mec element, it encodes PBP2a, which keeps cell wall synthesis going when native penicillin-binding proteins are blocked.
- Oxacillin and cefoxitin: oxacillin is the surrogate for methicillin, and cefoxitin is a better inducer of mecA in many strains, so it is the usual screening disc.
- Cefoxitin screen: under CLSI breakpoints, a 30 microgram cefoxitin disc with a zone of 21 mm or less indicates mecA-mediated resistance in Staphylococcus aureus.
- Vancomycin MIC: 2 micrograms per millilitre or less is susceptible, 4 to 8 is vancomycin-intermediate, and 16 or more is resistant.
- VISA: a thickened cell wall with excess D-alanyl-D-alanine targets traps vancomycin, and it usually emerges during prolonged therapy.
- VRSA: the vanA gene, acquired from vancomycin-resistant enterococci on the Tn1546 transposon, confers high-level resistance and is rare.
- Treatment: vancomycin remains the usual drug for serious MRSA infection, with linezolid, daptomycin or ceftaroline as alternatives depending on the site and the severity.
A stepwise laboratory workflow for MRSA
Correct reporting of MRSA depends on a sequence of checks, starting from a pure colony. The steps below follow the usual order in a diagnostic laboratory.
- Identify: colony morphology, catalase and tube coagulase confirm Staphylococcus aureus.
- Screen: a cefoxitin disc is placed on Mueller-Hinton agar, and the zone diameter is measured after overnight incubation.
- Confirm: a PBP2a latex agglutination test or a mecA PCR confirms the resistance mechanism.
- Test vancomycin: broth microdilution or an Etest gives the vancomycin MIC, which decides whether the isolate is VISA or VRSA.
- Report: the report names MRSA, gives the vancomycin MIC, and flags the isolate for infection control.
The screen detects resistance, while the MIC guides treatment. A clean cefoxitin result without a vancomycin MIC leaves the clinician unable to judge whether vancomycin will work. For this reason, many laboratories report the vancomycin MIC on every invasive MRSA isolate, not only on those that look unusual.
Where the exam tries to catch you
MRSA questions often test the difference between methicillin resistance and vancomycin resistance.
- Trap: calling MRSA vancomycin resistant Correct: MRSA is methicillin resistant but usually remains vancomycin susceptible, with an MIC of 2 micrograms per millilitre or less.
- Trap: treating a rising vancomycin MIC as a minor laboratory detail Correct: an MIC of 4 to 8 micrograms per millilitre signals VISA, which predicts treatment failure and calls for an alternative drug.
- Trap: assuming VRSA is widespread Correct: VRSA is rare, carries vanA acquired from enterococci, and each case is reported as an important event.
Frequently asked questions
What is the mechanism of methicillin resistance in MRSA?
Methicillin resistance in MRSA results from the mecA gene, which encodes penicillin-binding protein 2a with low affinity for beta-lactam antibiotics. PBP2a keeps cell wall synthesis going even when the native penicillin-binding proteins are inactivated by the drug.
What MIC defines vancomycin-intermediate Staphylococcus aureus?
Vancomycin-intermediate Staphylococcus aureus has a vancomycin MIC of 4 to 8 micrograms per millilitre under CLSI breakpoints. An MIC of 16 micrograms per millilitre or more places the isolate in the resistant category, which is the VRSA group.
Which gene confers vancomycin resistance in VRSA?
The vanA gene confers vancomycin resistance in VRSA, having been acquired from vancomycin-resistant enterococci on the Tn1546 transposon. VRSA is rare, and its detection leads to strict infection control measures and reporting.
Why is the cefoxitin disc used to screen for MRSA?
The cefoxitin disc is used because cefoxitin is a better inducer of mecA expression than oxacillin in many strains. Under CLSI breakpoints, a zone of 21 mm or less on the cefoxitin disc signals methicillin resistance in Staphylococcus aureus.