| Title | ACTIVITY OF TELAVANCIN AGAINST STAPHYLOCOCCI AND ENTEROCOCCI BY MIC AND RESISTANCE SELECTION STUDIES. | | Author(s) | Kosowska-Shick K, Clark C, Pankuch GA, McGhee P, Dewasse B, Beachel L, Appelbaum PC | | Institution | Department of Pathology, Hershey Medical Center, Hershey, PA 17033. | | Source | Antimicrob Agents Chemother 2009 Jul 20. | | Abstract | This study used CLSI broth microdilution to test the activity of telavancin and comparator antimicrobial agents against 67 methicillin-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 microg/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 heterogeneous VISA (hVISA) and VISA resistance phenotypes. In multistep resistance selection studies, telavancin yielded one stable mutant after 43 days in one MRSA out of the 10 MRSA tested with MIC rising eight-fold from 0.25 microg/ml (parent) to 2 microg/ml. MICs for this clone did not increase further when passages were continued for the maximum 50 days. By contrast, daptomycin selected stable resistant (MIC increase > 4x) clones after 14-35 days in four of 10 MRSA strains with MICs increasing from 1-2 microg/ml (parents) to 4-8 microg/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 14-21 days in two of 10 MRSA strains with MICs rising from 1-2 microg/ml (parents) to 4-16 microg/ml (stable resistant clones). Linezolid selected stable resistant clones after 22-48 days in two of 10 MRSA strains with MICs rising from 2-4 microg/ml (parents) to 32 microg/ml (resistant clones). Vancomycin yielded no resistant clones in 10 MRSA strains tested, however MICs increased two- to four-fold from 1-8 microg/ml to 2-16 microg/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 (<4.0x10(-11) to <2.9x10(-10) at 2x MIC) were lower than the spontaneous mutation frequencies obtained with the comparators. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19620338 |
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