Abstract
We assessed ceftaroline disk diffusion breakpoints for Staphylococcus aureus when applying revised Clinical and Laboratory Standards Institute (CLSI) ceftaroline MIC breakpoints. Disk-MIC correlation was evaluated by testing a challenge collection (n = 158) of methicillin-resistant S. aureus (MRSA) isolates composed of 106 randomly selected isolates plus 52 isolates with decreased susceptibility to ceftaroline (MIC, 1 to 16 μg/ml). Disk diffusion was performed with 30-μg disks and Mueller-Hinton agar from 2 manufacturers each. Revised CLSI susceptible (S)/susceptible dose-dependent (SDD)/resistant (R) MIC breakpoints of ≤1/2 to 4/≥8 μg/ml were applied. The disk breakpoints that provided the lowest error rates were CLSI S/R breakpoints of ≥25 mm/≤19 mm, with no very major (VM) or major (Ma) errors and with minor (Mi) error rates of 0.0% for ≥2 doubling dilutions above the I or SDD (≥I + 2), 22.1% for I or SDD plus or minus 1 doubling dilution (I ± 1), and 2.3% for ≤2 doubling dilutions below the I or SDD ≤I - 2 (overall Mi error rate, 16.5%). No mutation in the penicillin-binding protein 2a (PBP2a) was observed in 5 of 15 isolates with a ceftaroline MIC of 2 μg/ml; 3 of 11 isolates with a ceftaroline MIC of 1 μg/ml exhibited mutations in the penicillin-binding domain (PBD; 1 isolate) or in the non-PBD (2 isolates). All isolates except 1, with a ceftaroline MIC of ≥4 μg/ml, showed ≥1 mutation in the PBD and/or non-PBD. In summary, results from the disk diffusion method showed a good correlation with those from the reference broth microdilution method. Our results also showed that the ceftaroline MIC distribution of isolates with no mutations in the PBP2a goes up to 4 μg/ml, and reference broth microdilution and disk diffusion methods do not properly separate wild-type from non-wild-type isolates.
Highlights
We assessed ceftaroline disk diffusion breakpoints for Staphylococcus aureus when applying revised Clinical and Laboratory Standards Institute (CLSI) ceftaroline MIC breakpoints
The organism collection comprised a subset of 106 methicillin-resistant S. aureus (MRSA) isolates that were randomly selected from a collection of 1,596 MRSA clinical isolates recovered from non-U.S countries during the SENTRY program for 2016 and a subset of 52 clinical MRSA isolates with elevated ceftaroline MIC values (1 to 16 g/ml) that were included to provide a better evaluation of the categorical agreement between results from disk diffusion and broth microdilution methods
When error rates were analyzed for each disk separately, both disks displayed acceptable error rates, with no major or very major errors, and they had minor error rates of 0.0%, 14.2%, and 4.5% for disks were obtained from Hardy/MAST (disk A) and 0.0%, 29.6%, and 0.0% for disk B at ՆI ϩ 2, I Ϯ 1, and ՅI Ϫ 2, respectively
Summary
We assessed ceftaroline disk diffusion breakpoints for Staphylococcus aureus when applying revised Clinical and Laboratory Standards Institute (CLSI) ceftaroline MIC breakpoints. Disk-MIC correlation was evaluated by testing a challenge collection (n ϭ 158) of methicillin-resistant S. aureus (MRSA) isolates composed of 106 randomly selected isolates plus 52 isolates with decreased susceptibility to ceftaroline (MIC, 1 to 16 g/ml). All isolates except 1, with a ceftaroline MIC of Ն4 g/ ml, showed Ն1 mutation in the PBD and/or non-PBD. Results from the disk diffusion method showed a good correlation with those from the reference broth microdilution method. Our results showed that the ceftaroline MIC distribution of isolates with no mutations in the PBP2a goes up to 4 g/ml, and reference broth microdilution and disk diffusion methods do not properly separate wildtype from non-wild-type isolates
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