Ceftaroline pharmacodynamic activity versus community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus using an in vitro model.

BACKGROUND This study assessed the pharmacodynamics of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA), heteroresistant (h) vancomycin-intermediate S. aureus (hVISA), VISA and vancomycin-resistant S. aureus (VRSA) using an in vitro model. METHODS Two methicillin-susceptible S. aureus (MSSA), one community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, one hVISA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 × 10⁶ cfu/mL and ceftaroline dosed every 12 h (at 0 and 12 h) to simulate the ƒC(max) and t(½) obtained after administering 600 mg intravenously every 12 h (ƒC(max), 16 mg/L; t(½), 2.6 h). Samples were collected over 24 h to assess viable growth and changes in ceftaroline MIC over time. RESULTS Ceftaroline ƒT(> MIC) of ≥ 92% (ceftaroline MICs, ≤ 1 mg/L) was bactericidal (≥ 3 log₁₀ killing) against MSSA, CA-MRSA, HA-MRSA, hVISA, VISA and VRSA at 12 and 24 h. No bacterial regrowth occurred over the study period and no change in ceftaroline MIC was observed. CONCLUSIONS Ceftaroline ƒT(> MIC) of ≥ 92% (ceftaroline MICs, ≤ 1 mg/L) was bactericidal (≥ 3 log₁₀ killing) against MSSA, CA-MRSA, HA-MRSA, hVISA, VISA and VRSA at 12 and 24 h.