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 ƒCmax and t1/2 obtained after administering 600 mg intravenously every 12 h (ƒCmax, 16 mg/L; t1/2, 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.
Zhanel GG, Rossnagel E, Nichol K, Cox L, Karlowsky JA, Zelenitsky S, Noreddin AM, Hoban DJ. 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. J Antimicrob Chemother. 2011;66(6):1301-5. doi: 10.1093/jac/dkr110