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Antimicrobial Agents and Chemotherapy, November 2009, p. 4712-4717, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00636-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Activity of Ceftaroline against Methicillin-Resistant Staphylococcus aureus and Heterogeneous Vancomycin-Intermediate S. aureus in a Hollow Fiber Model{triangledown}

Céline Vidaillac,1 Steve N. Leonard,1,3,{dagger} and Michael J. Rybak1,2,3*

Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences,1 School of Medicine, Wayne State University, Detroit, Michigan 48201,2 Detroit Receiving Hospital, Detroit, Michigan 482013

Received 11 May 2009/ Returned for modification 3 August 2009/ Accepted 28 August 2009

Ceftaroline is a broad-spectrum injectable cephalosporin exhibiting bactericidal activity against a variety of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Using a two-compartment in vitro pharmacokinetic/pharmacodynamic (PK/PD) model, we evaluated the activity of ceftaroline at 600 mg every 8 h (q8h) and q12h in comparison with that of vancomycin at 1,000 mg q12h over a 72-h time period against six clinical MRSA isolates, including two heterogeneous vancomycin-intermediate S. aureus (hVISA) isolates. The MIC and minimum bactericidal concentration ranged between 0.125 to 2 and 0.5 to 2 µg/ml for ceftaroline and vancomycin, respectively. In the PK/PD model, ceftaroline was superior to vancomycin against all isolates (P < 0.05), except one to which it was equivalent. No difference in activity was observed between both q8 and q12h dosing regimens of ceftaroline. Bacterial regrowth was observed after 32 h for two isolates treated with ceftaroline. This regrowth was uncorrelated to resistance, instability of the drug, or tolerance. However, subpopulations with higher MICs to ceftaroline were found by population analysis for these two isolates. Finally, and in contrast to ceftaroline, MIC elevations up to 8 to 12 µg/ml were observed with vancomycin for the hVISA isolates. In conclusion, in addition to a lower potential to select resistant mutants, ceftaroline demonstrated activity equal to or greater than vancomycin against MRSA isolates. Although further in vitro and in vivo investigations are warranted, ceftaroline appears to be a promising alternative for the treatment of MRSA infections.

* Corresponding author. Mailing address: Anti-Infective Research Laboratory, Pharmacy Practice—4148, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201. Phone: (313) 577-4376. Fax: (313) 577-8915. E-mail: m.rybak{at}wayne.edu

{triangledown} Published ahead of print on 8 September 2009.

{dagger} Present address: Northeastern University, School of Pharmacy, Boston, MA 02115.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4712-4717, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00636-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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