Susceptibility testing challenges with ceftaroline, MRSA and a 1 mg/L breakpoint.

Area of Science:

• Clinical Microbiology
• Antimicrobial Susceptibility Testing
• Infectious Diseases

Background:

• A 1 mg/L breakpoint for ceftaroline susceptibility in staphylococci is widely accepted.
• Discrepancies exist between EUCAST, CLSI, and FDA breakpoints for ceftaroline, impacting resistance interpretation.
• Reliable differentiation of minimum inhibitory concentrations (MICs) of 1 mg/L versus 2 mg/L is crucial for effective treatment.

Purpose of the Study:

• To evaluate the reliability of routine diagnostic methods in distinguishing ceftaroline MICs of 1 mg/L versus 2 mg/L in Staphylococcus aureus.
• To assess the performance of different disc diffusion and Etest methods compared to central agar dilution reference methods.

Main Methods:

• Thirty-five UK laboratories tested Staphylococcus aureus isolates using EUCAST (5 μg) or CLSI (30 μg) disc diffusion methods on Mueller-Hinton or Iso-Sensitest agar.
• Etests were performed for Methicillin-resistant Staphylococcus aureus (MRSA) isolates.
• Central MIC determination was conducted using CLSI and BSAC agar dilution methods.

Main Results:

• Analysis of 1607 S. aureus isolates (33% MRSA) revealed poor discrimination between MICs of 1 and 2 mg/L by routine methods.
• EUCAST and CLSI disc diffusion methods showed low positive predictive values for resistance (11.0% and 13.4%, respectively).
• Essential agreement between Etests and agar dilution was high (>95%), but agreement on non-susceptibility was low (20%).

Conclusions:

• Routine methods demonstrate poor discrimination for ceftaroline MICs of 1 mg/L and 2 mg/L in MRSA.
• Systematic bias was observed in zone diameter interpretations across different laboratories and methods.
• Improved standardization, automation, or adjustment of ceftaroline breakpoints are recommended for accurate susceptibility testing.