Since it is unknown whether β-lactam antimicrobial agents can be used 
effectively against borderline oxacillin-resistant Staphylococcus aureus (BORSA) 
with oxacillin MICs ≥4 mg/L, the in vitro bactericidal activity and 
pharmacodynamic effect of oxacillin against clinical BORSA isolates was 
evaluated. Time-kill experiments with oxacillin were performed and the results 
compared with those obtained with vancomycin, daptomycin and linezolid against 
BORSA with oxacillin MICs ≥4 mg/L and BORSA with oxacillin MICs ≤2 mg/L. 
Furthermore, the effect of β-lactamase production and plasmid profile analysis 
were taken into account to clarify responses to oxacillin. Oxacillin killing 
activity was attenuated against BORSA compared with ATCC 29213 since the 
pharmacodynamic parameters revealed that the potency of oxacillin was markedly 
reduced (c. ten-fold) against BORSA with oxacillin MICs ≥4 mg/L. pBORa53-like 
plasmid-containing BORSA with oxacillin MICs ≤2 mg/L showed markedly more 
regrowth. In conclusion, oxacillin was non-effective in the eradication of 
either (i) BORSA with oxacillin MICs ≥4 mg/L or (ii) β-lactamase-hyperproducing 
BORSA (MICs ≤2 mg/L). Further investigation into β-lactam dosing strategies 
against different BORSA strains is warranted in order to avoid possible therapy 
failure.