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Antimicrobial Agents and Chemotherapy, February 2009, p. 552-556, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.01324-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Evaluation of the Antimicrobial Activity of Ceftaroline against Cephalosporin-Resistant Isolates of Streptococcus pneumoniae{triangledown}

Lesley McGee,1,4* Donald Biek,2 Yigong Ge,2 Magderie Klugman,1 Mignon du Plessis,3 Anthony M. Smith,3 Bernard Beall,4 Cynthia G. Whitney,4 and Keith P. Klugman1

Emory University, Atlanta, Georgia,1 Cerexa, Inc., Alameda, California,2 National Institute for Communicable Diseases, Sandringham, South Africa,3 Centers for Disease Control and Prevention, Atlanta, Georgia4

Received 2 October 2008/ Returned for modification 31 October 2008/ Accepted 9 November 2008

Increasing pneumococcal resistance to extended-spectrum cephalosporins warrants the search for novel agents with activity against such resistant strains. Ceftaroline, a parenteral cephalosporin currently in phase 3 clinical development, has demonstrated potent in vitro activity against resistant gram-positive organisms, including penicillin-resistant Streptococcus pneumoniae. In this study, the activity of ceftaroline was evaluated against highly cefotaxime-resistant isolates of pneumococci from the Active Bacterial Core surveillance program of the Centers for Disease Control and Prevention and against laboratory-derived cephalosporin-resistant mutants of S. pneumoniae. The MICs of ceftaroline and comparators were determined by broth microdilution. In total, 120 U.S. isolates of cefotaxime-resistant (MIC ≥ 4 µg/ml) S. pneumoniae were tested along with 18 laboratory-derived R6 strains with known penicillin-binding protein (PBP) mutations. Clinical isolates were characterized by multilocus sequence typing, and the DNAs of selected isolates were sequenced to identify mutations affecting pbp genes. Ceftaroline (MIC90 = 0.5 µg/ml) had greater in vitro activity than penicillin, cefotaxime, or ceftriaxone (MIC90 = 8 µg/ml for all comparators) against the set of highly cephalosporin-resistant clinical isolates of S. pneumoniae. Ceftaroline was also more active against the defined R6 PBP mutant strains, which suggests that ceftaroline can overcome common mechanisms of PBP-mediated cephalosporin resistance. These data indicate that ceftaroline has significant potency against S. pneumoniae strains resistant to existing parenteral cephalosporins and support its continued development for the treatment of infections caused by resistant S. pneumoniae strains.

* Corresponding author. Mailing address: Hubert Department of Global Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-3984. Fax: (404) 727-4590. E-mail: lmcgee{at}sph.emory.edu

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 552-556, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.01324-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pankuch, G. A., Appelbaum, P. C. (2009). Postantibiotic Effect of Ceftaroline against Gram-Positive Organisms. Antimicrob. Agents Chemother. 53: 4537-4539 [Abstract] [Full Text]  


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