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

Objectives A 1 mg/L susceptibility breakpoint for ceftaroline and staphylococci is universally agreed; EUCAST counts MIC >1 mg/L as resistant whereas CLSI and FDA count 2 mg/L as intermediate and >2 mg/L as resistant. We investigated whether routine diagnostic tests reliably distinguish MICs of 1 versus 2 mg/L.Methods Thirty-five UK laboratories collected Staphylococcus aureus isolates and performed tests with 5 μg (as EUCAST) or 30 μg (as CLSI) discs and either confluent growth on Mueller–Hinton agar (as EUCAST and CLSI) or semi-confluent growth on Iso-Sensitest agar (as BSAC). They also ran Etests for MRSA. Reference MICs were determined centrally by CLSI and BSAC agar dilution.Results We obtained paired local disc and central MIC results for 1607 S. aureus (33% MRSA). EUCAST's zone breakpoint recognized 56% of isolates found resistant in MIC tests, but the positive predictive value (PPV) for resistance was 11.0%; corresponding proportions by CLSI testing were 28.0% and 13.4%. The BSAC disc method detected 25% of resistant isolates, with a PPV of 18.2%. Essential agreement, ±1 dilution, of local Etests and central agar MICs was >95%, but only 20% of the isolates found non-susceptible by agar dilution were found non-susceptible by Etest and vice versa. Review for isolates with the modal MIC (0.25 mg/L) indicated that the same laboratories reported large or small zones irrespective of disc and method, implying systematic bias.Conclusions MRSA with ceftaroline MICs of 1 and 2 mg/L were poorly discriminated by routine methods. Solutions lie in greater standardization, automation or dosages justifying a higher breakpoint.