Effects of ceftobiprole and oxacillin on mecA expression in methicillin-resistant Staphylococcus aureus clinical

Wenchi Shang1, Todd A Davies, Robert K Flamm

  • 1Johnson & Johnson Pharmaceutical Research & Development LLC, 1000 Route 202 South, Raritan, NJ 08869, USA. wshang2@its.jnj.com

Insights

Ceftobiprole and oxacillin induced the mecA gene in methicillin-resistant Staphylococcus aureus. However, the induction levels did not correlate with antibiotic resistance, suggesting complex resistance mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat.
  • The mecA gene is crucial for MRSA's resistance to beta-lactam antibiotics.
  • Understanding mecA induction is vital for developing effective treatment strategies.

Purpose of the Study:

  • To investigate the induction of the mecA gene by ceftobiprole and oxacillin in clinical MRSA isolates.
  • To determine the correlation between mecA induction levels and antibiotic minimum inhibitory concentrations (MICs).
  • To explore the relationship between mecA induction and Staphylococcal Cassette Chromosome mec (SCCmec) types.

Main Methods:

  • Studied 18 clinical MRSA isolates with diverse SCCmec cassettes.
  • Quantified mecA gene induction using reverse transcriptase PCR (RT-PCR).
  • Determined MICs for ceftobiprole and oxacillin.

Main Results:

  • mecA induction varied significantly (3-65 fold for ceftobiprole, 2-69 fold for oxacillin).
  • No correlation was observed between mecA induction magnitude and ceftobiprole MICs.
  • High oxacillin MICs (≥256 µg/ml) were associated with substantial oxacillin-induced mecA expression (≥13 fold) in 11 isolates.
  • No association found between mecA induction levels and SCCmec type.

Conclusions:

  • Ceftobiprole and oxacillin can induce mecA expression in MRSA.
  • mecA induction levels do not consistently predict ceftobiprole resistance.
  • High-level oxacillin resistance in some MRSA strains correlates with significant mecA induction.
  • SCCmec type does not appear to influence the magnitude of mecA induction by these antibiotics.

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