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Antimicrobial Agents and Chemotherapy, June 2007, p. 2043-2047, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.00131-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Time-Kill and Synergism Studies of Ceftobiprole against Enterococcus faecalis, Including ß-Lactamase-Producing and Vancomycin-Resistant Isolates{triangledown}

Cesar A. Arias,1,2,4 Kavindra V. Singh,1,2 Diana Panesso,4 and Barbara E. Murray1,2,3*

Center for the Study of Emerging and Reemerging Pathogens, Division of Infectious Diseases,1 Department of Internal Medicine,2 Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas 77030,3 Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, Colombia4

Received 29 January 2007/ Returned for modification 19 March 2007/ Accepted 5 April 2007

Ceftobiprole (BAL9141) is an investigational cephalosporin with broad in vitro activity against gram-positive cocci, including enterococci. Ceftobiprole MICs were determined for 93 isolates of Enterococcus faecalis (including 16 ß-lactamase [Bla] producers and 17 vancomycin-resistant isolates) by an agar dilution method following the Clinical and Laboratory Standards Institute recommendations. Ceftobiprole MICs were also determined with a high inoculum concentration (107 CFU/ml) for a subset of five Bla producers belonging to different previously characterized clones by a broth dilution method. Time-kill and synergism studies (with either streptomycin or gentamicin) were performed with two ß-lactamase-producing isolates (TX0630 and TX5070) and two vancomycin-resistant isolates (TX2484 [VanB] and TX2784 [VanA]). The MICs of ceftobiprole for 50 and 90% of the isolates tested were 0.25 and 1 µg/ml, respectively. All Bla producers and vancomycin-resistant isolates were inhibited by concentrations of ≤1 and ≤4 µg/ml, respectively, at the standard inoculum concentration. Ceftobiprole MICs at a high inoculum concentration for a subset of five Bla+ E. faecalis isolates were ≤1 µg/ml. Bactericidal activity was observed against four isolates tested at concentrations as low as 1 µg/ml regardless of the production of ß-lactamase or vancomycin resistance. A combination of ceftobiprole (0.5 µg/ml) and streptomycin (25 µg/ml) was synergistic against Bla+ TX0630 and TX5070. Ceftobiprole (0.5 µg/ml) plus gentamicin (10 µg/ml) was synergistic against VanB isolate TX2484 and showed enhanced killing, but not synergism, against TX2784 (VanA), despite the absence of high-level resistance to gentamicin. In conclusion, ceftobiprole exhibited good in vitro activity against E. faecalis, including Bla+ and vancomycin-resistant strains, and exhibited synergism with aminoglycosides against selected isolates.

* Corresponding author. Mailing address: 6431 Fannin St., Room 2,112 MSB, University of Texas Medical School, Houston, TX 77030. Phone: (713) 500-6745. Fax: (713) 500-6766. E-mail: bem.asst{at}uth.tmc.edu

{triangledown} Published ahead of print on 16 April 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 2043-2047, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.00131-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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