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

Livermore, David M. ORCID:, Mushtaq, Shazad, Warner, Marina, James, Dorothy and Woodford, Neil (2015) Susceptibility testing challenges with ceftaroline, MRSA, and a 1-mg/L breakpoint. Journal of Antimicrobial Chemotherapy, 70 (12). pp. 3259-3266. ISSN 0305-7453

[thumbnail of Ceftaroline_testing_revised_pdf]
PDF (Ceftaroline_testing_revised_pdf) - Accepted Version
Download (1MB) | Preview


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.

Item Type: Article
Uncontrolled Keywords: disc susceptibility tests,etests,meticillin-resistant staphylococcus aureus
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health
Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User: Pure Connector
Date Deposited: 13 Nov 2015 15:00
Last Modified: 21 Oct 2022 01:07
DOI: 10.1093/jac/dkv265


Downloads per month over past year

Actions (login required)

View Item View Item