It’s Not You, It’s SOSA: A Case Study on Breaking Up With an FDA-Cleared Susceptibility Testing System’s Oxacillin Results for Staphylococcus spp. Other Than S. aureus and S. lugdunensis

Abstract Background In 2021, the Clinical and Laboratory Standards Institute revised its susceptible oxacillin minimum inhibitory concentration (MIC) breakpoint for Staphylococcus spp. other than S. aureus and S. lugdunensis (SOSA) from ≤0.25 to ≤0.5 µg/mL. Here, we describe the response to this breakpoint change, which at the time of this study was not yet recognized by the US Food and Drug Administration (FDA), in our laboratory, where the primary method for antimicrobial susceptibility testing (AST) of SOSA is VITEK 2. VITEK 2 uses the Automated Expert System (AES) to integrate the results of oxacillin MIC and cefoxitin screen tests into a final interpretation; our laboratory also adjudicates discordant oxacillin and cefoxitin results using a PBP2a test. Methods We retrospectively reviewed and assessed the yield of PBP2a testing for 189 SOSA isolates with discordant (when applying the FDA susceptible oxacillin breakpoint of ≤0.25 µg/mL) VITEK 2 oxacillin and cefoxitin results, and then prospectively incorporated PBP2a testing for isolates with oxacillin MICs of 0.5 µg/mL and positive cefoxitin screens into our algorithm. Results Compared with accepting the VITEK 2 AES interpretation, PBP2a testing substantially improved the accuracy of mecA-mediated resistance classification in both scenarios, especially for the ∼4.7% of isolates with oxacillin MICs ≤0.5 µg/mL and positive cefoxitin screens. Conclusions Although detection of mecA or PBP2a is the gold standard for assessment of β-lactam resistance in staphylococci, targeting a subset of isolates for mecA or PBP2a testing based on phenotypic AST results that predict an increased risk of misclassification may be a pragmatic, labor- and cost-saving approach. Targeting selected staphylococci for PBP2a testing based on VITEK 2 phenotypic susceptibility testing results is a pragmatic approach for clinical laboratories to increase the accurate classification of mecA-mediated oxacillin resistance among Staphylococcus spp. other than S. aureus and S. lugdunensis.