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Antimicrobial Agents and Chemotherapy, October 2009, p. 4217-4224, Vol. 53, No. 10
0066-4804/09/$08.00+0 doi:10.1128/AAC.00742-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Activity of Telavancin against Staphylococci and Enterococci Determined by MIC and Resistance Selection Studies
Klaudia Kosowska-Shick,
Catherine Clark,
Glenn A. Pankuch,
Pamela McGhee,
Bonifacio Dewasse,
Linda Beachel, and
Peter C. Appelbaum*
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033
Received 3 June 2009/ Returned for modification 30 June 2009/ Accepted 3 July 2009
This study used CLSI broth microdilution to test the activity of telavancin and comparator antimicrobial agents against 67 methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates. Twenty-six vancomycin-intermediate S. aureus (VISA) strains were among the isolates tested; all strains were susceptible to telavancin at 
1 µg/ml, whereas 12/26 (46%) of these isolates were nonsusceptible to daptomycin at the same concentration. All strains were susceptible to quinupristin-dalfopristin, while resistance was found to all other drugs tested. Telavancin demonstrated potent activity against all vancomycin-susceptible isolates as well as against heterogeneously VISA and VISA resistance phenotypes. In multistep resistance selection studies, telavancin yielded one stable mutant after 43 days in one MRSA strain out of the 10 MRSA strains tested with the MIC rising eightfold from 0.25 µg/ml (parent) to 2 µg/ml. MICs for this clone did not increase further when passages were continued for the maximum 50 days. In contrast, daptomycin selected stable resistant clones (MIC increase of >4x) after 14 to 35 days in 4 of 10 MRSA strains with MICs increasing from 1 to 2 µg/ml (parents) to 4 to 8 µg/ml (resistant clones). Sequencing analysis of daptomycin resistance determinants revealed point mutations in the mprF genes of all four stable daptomycin-resistant clones. Teicoplanin gave rise to resistant clones after 14 to 21 days in 2 of 10 MRSA strains with MICs rising from 1 to 2 µg/ml (parents) to 4 to 16 µg/ml (stable resistant clones). Linezolid selected stable resistant clones after 22 to 48 days in 2 of 10 MRSA strains with MICs rising from 2 to 4 µg/ml (parents) to 32 µg/ml (resistant clones). Vancomycin yielded no resistant clones in 10 MRSA strains tested; however, MICs increased two- to fourfold from 1 to 8 µg/ml to 2 to 16 µg/ml after 50 days. No cross-resistance was found with any clone/antimicrobial combination. The two enterococci developed resistance to daptomycin, and one developed resistance to linezolid. Single-step mutation frequencies for telavancin (<4.0 x 10–11 to <2.9 x 10–10 at 2x MIC) were lower than the spontaneous mutation frequencies obtained with the comparators.
* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psu.edu
Published ahead of print on 20 July 2009.
Antimicrobial Agents and Chemotherapy, October 2009, p. 4217-4224, Vol. 53, No. 10
0066-4804/09/$08.00+0 doi:10.1128/AAC.00742-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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