Evaluating veterinary Staphylococcus β-lactam breakpoint performance: a comparative analysis of individual agents...

Staphylococcus pseudintermedius is an important pathogen in companion animals. Accurate detection and reporting of mecA-mediated resistance to β-lactam antimicrobials is essential for guiding appropriate antimicrobial treatments. While surrogate agents are used in human diagnostic laboratories to predict β-lactam results in staphylococci, individual β-lactam breakpoints are published for veterinary staphylococci, discouraging the use of a surrogate. Comparative performance of these individual β-lactam breakpoints to predict methicillin-resistance in veterinary Staphylococcus species has not been previously evaluated. This study evaluated oxacillin's accuracy at detecting mecA presence and performance as a surrogate for β-lactams in S. pseudintermedius from canids and felids. Antimicrobial susceptibility data for S. pseudintermedius were obtained from clinical isolates (n = 1,914) from veterinary diagnostic laboratories across the United States and Canada and included broth microdilution results for amoxicillin-clavulanate, cefazolin, cefovecin, cefpodoxime, cephalothin, and oxacillin, along with the corresponding presence or absence of mecA. Agreement analysis, sensitivities, and specificities were calculated to compare oxacillin performance with individual β-lactams. Oxacillin demonstrated the highest sensitivity for the prediction of mecA-mediated resistance among all antimicrobials analyzed. For isolates possessing mecA, the proportion showing resistant minimum inhibitory concentrations to β-lactams other than oxacillin was low, ranging between 16.5% and 85%. Additionally, when compared to oxacillin, all β-lactams other than cefovecin exhibited high rates of very major discrepancies, corroborating the significant risk of reporting false susceptibility when testing these antimicrobials. These findings support utilizing oxacillin as a surrogate agent for predicting β-lactam interpretations and emphasize the necessity for clarified guidance in the Clinical Laboratory Standards Institute VET01S document.IMPORTANCEAccurate testing and reporting of β-lactam antimicrobials in Staphylococcus species are essential for guiding appropriate antimicrobial therapy in companion animals. Our findings show that oxacillin is the most sensitive antimicrobial for detecting mecA-mediated resistance when testing Staphylococcus pseudintermedius, while most other β-lactams have low sensitivity for mecA and unacceptable rates of very major discrepancies when compared to oxacillin. These results highlight the risk of reporting falsely reporting β-lactam results when interpretations are based solely on testing each individual agent. Therefore, oxacillin and cefoxitin should be used as surrogate markers for β-lactam susceptibility, as appropriate for the Staphylococcus species, to minimize the risk of reporting false susceptible results. The clarification of these criteria by the Clinical and Laboratory Standards Institute in VET01S will enhance diagnostic accuracy, aid effective antimicrobial stewardship, and improve clinical outcomes in veterinary medicine.