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JAC Advance Access originally published online on May 19, 2009
Journal of Antimicrobial Chemotherapy 2009 64(2):364-369; doi:10.1093/jac/dkp176
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Pharmacodynamic activity of ceftobiprole compared with vancomycin versus methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) using an in vitro model

George G. Zhanel1,2,3,*, Dylan Voth1, Kim Nichol1,2, James A. Karlowsky1,2, Ayman M. Noreddin4 and Daryl J. Hoban1,2

1 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada 2 Department of Clinical Microbiology, Health Sciences Centre, Winnipeg, Manitoba, Canada 3 Department of Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada 4 College of Pharmacy, University of Minnesota, Duluth, MN, USA

Received 26 February 2009; returned 15 April 2009; revised 23 April 2009; accepted 23 April 2009

* Corresponding author. Microbiology, Health Sciences Centre, MS673–820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada. Tel: +1-204/787-4902; Fax: +1-204/787-4699; E-mail: ggzhanel{at}pcs.mb.ca

Background: This study compared the pharmacodynamics of ceftobiprole and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) using an in vitro model.

Methods: Two methicillin-susceptible S. aureus (MSSA), two community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 x 106 cfu/mL and ceftobiprole dosed every 8 h (at 0, 8 and 16 h) to simulate the fCmax and t1/2 obtained after 500 mg intravenous (iv) every 8 h dosing (fCmax, 30 mg/L; t1/2, 3.5 h). Vancomycin was dosed every 12 h (at 0 and 12 h) to simulate fCmax and t1/2 obtained after 1 g iv every 12 h dosing (fCmax, 20 mg/L; t1/2, 8 h). Samples were collected over 24 h to assess viable growth.

Results: Ceftobiprole T > MIC of ≥100% (ceftobiprole MICs, ≤2 mg/L) was bactericidal (≥3 log10 killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin fAUC24/MIC of 340 (vancomycin MIC, 1 mg/L for MSSA and MRSA) resulted in a 1.8–2.6 log10 reduction in colony count at 24 h. Vancomycin fAUC24/MIC of 85–170 (vancomycin MIC, 2–4 mg/L for VISA) resulted in a 0.4–0.7 log10 reduction at 24 h. Vancomycin fAUC24/MIC of 5.3 (vancomycin MIC, 64 mg/L for VRSA) resulted in a limited effect.

Conclusions: Ceftobiprole T > MIC of ≥100% (ceftobiprole MICs, ≤2 mg/L) was bactericidal (≥3 log10 killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin was bacteriostatic against MSSA, MRSA and VISA, while demonstrating no activity against VRSA.

Keywords: bactericidal , bacterial killing , inhibition


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