What does the presence of mecA (methicillin-resistant gene A) or mecC (methicillin-resistant gene C) indicate in a bacterial isolate?

Understanding mecA and mecC Genes in Bacterial Isolates

The presence of mecA or mecC genes in a bacterial isolate definitively indicates methicillin resistance, most commonly in Staphylococcus aureus, conferring resistance to all commercially available β-lactam antibiotics and requiring alternative antimicrobial treatment strategies. 1

Molecular Basis of Methicillin Resistance

mecA Gene

• Encodes a modified penicillin-binding protein (PBP2a) with reduced affinity for β-lactam antibiotics 1
• Carried on mobile genetic elements called Staphylococcal Cassette Chromosome mec (SCCmec) 1
• SCCmec elements contain two essential components:
  • mec gene complex (contains mecA)
  • ccr gene complex (contains site-specific recombinase genes) 1
• Strains carrying mecA are resistant to all commercially available β-lactams 1

mecC Gene

• A homolog of mecA (shares 63% similarity) 2
• More recently discovered variant that also confers methicillin resistance
• Also carried on SCCmec elements (typically SCCmecXI) 3
• Encodes a transpeptidase enzyme functionally similar to PBP2a 2

Clinical Significance

Diagnostic Implications

• Molecular detection of mecA/mecC is the most accurate method for identifying methicillin resistance 1
• Rapid molecular identification of these genes allows for:
  • Earlier initiation of appropriate antimicrobial therapy 1
  • Reduced mortality in serious infections 1
  • Better antimicrobial stewardship 1

Treatment Implications

• Isolates positive for mecA or mecC require non-β-lactam antibiotics 1
• Recommended treatment options include:
  • Vancomycin (first-line for MRSA infections) 1
  • Linezolid 1
  • Daptomycin 1
  • Teicoplanin 2
  • Trimethoprim-sulfamethoxazole (for less severe infections) 1
  • Tetracyclines (doxycycline or minocycline) 1

Epidemiological Considerations

mecA vs. mecC Distribution

• mecA is far more prevalent globally than mecC 4
• In a multi-center study in Pakistan (2023), among MRSA isolates:
  • 31.8% carried mecA alone
  • 7.9% carried mecC alone
  • 57.1% carried both mecA and mecC 2
• mecC has been detected in several European countries but may be absent in certain regions 4, 3

Clinical Presentation

• Both mecA and mecC positive isolates can cause severe infections, including fatal bacteremia 3
• No significant difference in virulence has been established between mecA and mecC positive strains

Testing Considerations

• Molecular methods (PCR) are superior to phenotypic testing for detecting mecA/mecC 5
• Rapid diagnostic tests that detect these genes improve time to appropriate therapy 1
• Some discrepancies between genotypic and phenotypic resistance determination can occur, though rare 1
• Nucleic acid lateral flow immunoassays (NALFIA) offer rapid, reliable detection of both mecA and mecC genes 6

Important Caveats

• Detection of mecA/mecC alone doesn't identify the bacterial species - additional testing is needed to confirm the organism is S. aureus or another staphylococcal species 6
• Some methicillin-resistant isolates may lack both mecA and mecC, suggesting alternative resistance mechanisms 4
• Heterogeneous expression of methicillin resistance can complicate phenotypic susceptibility testing 5
• Always correlate molecular findings with clinical presentation and conventional culture results for optimal patient management