MRSA Detection: The EUCAST Guide for FRCPath Candidates

By FRCPath Prep Consultant

In the FRCPath Part 1 and Part 2 exams, few topics are as "high yield" as antimicrobial susceptibility testing. Specifically, the detection of Methicillin-Resistant Staphylococcus aureus (MRSA) is a cornerstone of laboratory safety.

Examiners expect you to know not just the "what" (the breakpoints) but the "why" (the mechanisms). While automated systems (Vitek, Phoenix) often handle this in the lab, you must understand the manual disk diffusion criteria defined by EUCAST, as this is frequently tested in the Part 2 OSPE.

The Mechanism: Why Methicillin?

Resistance to anti-staphylococcal beta-lactams (methicillin, oxacillin, flucloxacillin) is primarily driven by the acquisition of the mecA gene (or the homologue mecC).

• Normal: Staphylococci produce Penicillin-Binding Proteins (PBPs) that build the cell wall.

• MRSA: The mecA gene codes for PBP2a (or PBP2' in mecC strains). PBP2a has a low affinity for beta-lactams. Even in the presence of flucloxacillin, PBP2a continues to synthesize the cell wall, allowing the bacteria to survive.

The Surrogate: Why Cefoxitin?

Historically, we used Methicillin or Oxacillin disks. However, Cefoxitin is now the preferred surrogate marker for mecA-mediated resistance.

Why? Cefoxitin is a potent inducer of the mecA gene. It is much more sensitive than oxacillin for detecting low-level resistant populations (heteroresistance), making it the gold standard for phenotypic detection.

The EUCAST Criteria (The Rules)

You cannot blindly apply a "one size fits all" rule to staphylococci. The zone diameter breakpoints for the 30 µg Cefoxitin disk differ based on the species. Memorizing these distinctions is crucial for the exam.

1. The Standard Rule

Target: Staphylococcus aureus and most Coagulase-Negative Staphylococci (CoNS). Note: This excludes S. epidermidis, S. lugdunensis, and the S. pseudintermedius group.

Result	Zone Diameter (30 µg Cefoxitin)
Sensitive (S)	≥ 22 mm
Resistant (R)	< 22 mm

Interpretation: If the zone is < 22 mm, report as MRSA. The isolate is resistant to all beta-lactams (penicillins, cephalosporins, carbapenems) except those specifically active against MRSA (e.g., Ceftaroline, Ceftobiprole).

2. The "Epi/Lug" Rule

Target: S. epidermidis and S. lugdunensis. These species have different PBP expression levels, requiring a stricter cutoff to avoid false susceptibility.

Result	Zone Diameter (30 µg Cefoxitin)
Sensitive (S)	≥ 27 mm
Resistant (R)	< 27 mm

Examiner’s Trap: A zone of 24 mm is Sensitive for S. aureus but Resistant for S. epidermidis. Check the organism ID before measuring the zone!

3. The Veterinary Exception (S. pseudintermedius)

Target: S. pseudintermedius, S. intermedius, S. schleiferi, S. coagulans. These are often zoonotic pathogens (dog bites). For these species, Cefoxitin is not a reliable marker. You must use Oxacillin.

Result	Zone Diameter (1 µg Oxacillin)
Sensitive (S)	≥ 20 mm
Resistant (R)	< 20 mm

Part 2 OSPE Tips

In an OSPE station, you might be presented with a plate and a ruler.

1. Identify the Organism First: Is it S. aureus or CoNS?

2. Select the Right Breakpoint: 22 mm vs 27 mm.

3. Check for "Haze": Look closely within the zone of inhibition. Any growth within the zone (even a light haze) indicates resistance, regardless of the diameter.

4. Know the Limitations: Cefoxitin detects mecA/mecC. It does not detect rare mechanisms like hyper-production of beta-lactamase (BORSA - Borderline Oxacillin Resistant S. aureus), though these are clinically treated as MRSA anyway.

Mastering these nuances separates the safe Consultant from the uncertain trainee. For more detailed guides and mock OSPE stations, visit FRCPathprep.com.