Re-examining cephalosporin activity against methicillin-susceptible Staphylococcus aureus among clinical isolates from southern Taiwan

Background: (MSSA) is typically inferred from oxacillin or cefoxitin results; however, the reliability of this surrogate approach remains uncertain. This study aimed to evaluate MSSA susceptibility to first- through fifth-generation cephalosporins and assess the predictive value of oxacillin minimum inhibitory concentrations (MICs) for identifying non-susceptibility. Methods: A total of 514 MSSA bloodstream isolates were collected from two hospitals in Taiwan. MICs for oxacillin and various cephalosporins were determined using broth microdilution. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of oxacillin MICs. Multilocus sequence typing (MLST) was performed on isolates exhibiting ceftaroline resistance or the susceptible-dose dependent (SDD) phenotype to examine their genetic diversity. Results: Non-susceptibility rates ranged from 4.9% to 6.2% for cefazolin, cefuroxime, ceftriaxone, and cefepime. For ceftaroline, while resistance was uncommon (1.4%), a notable proportion of isolates (9.7%) exhibited the SDD phenotype. An oxacillin MIC ≥0.25 mg/L predicted non-susceptibility to first- through fourth-generation cephalosporins with high accuracy (area under the curve [AUC] 0.827-0.875; negative predictive value [NPV] ≥ 98.7%) but was less predictive for ceftaroline (AUC 0.614). Among 44 isolates with elevated ceftaroline MICs, MLST identified 36 distinct sequence types, including 25 novel ones, indicating substantial genetic diversity. Conclusions: Cephalosporin non-susceptibility can occur among MSSA isolates. Although elevated oxacillin MICs were associated with higher MICs for several cephalosporins, this relationship was less predictive for ceftaroline. These findings highlight microbiological variability in MSSA cephalosporin susceptibility and may inform situations where direct MIC testing provides additional clarity.