A baseline assessment of telavancin's activity against a collection of Gram-positive isolates, including resistant phenotypes

Abstract number: 1134_03_322

Draghi D.C., Blosser R., Jones M., Sahm D.F.

Objectives:  

As new antimicrobial agents are developed, it is important to examine their in vitro activity against a collection of organisms for which they are targeted. Telavancin (TLV) is a rapidly bactericidal lipoglycopeptide with multiple mechanisms of action that is in Phase 3 development for the treatment of serious infections caused by gram-positive pathogens. The current study examines the in vitro activity of TLV against 101 staphylococci, Enterococci, and Streptococci, including clinically-relevant resistant phenotypes.

Methods:  

50 Staphylococcus aureus (SA), 11 coagulase-negative Staphylococci (CNS), 10 Enterococcus faecalis (EF), 10 Enterococcus faecium (EM), 10 Streptococcus pneumoniae (SP), and 10 other Streptococcus spp. (STR) were tested against TLV and comparator agents by broth microdilution (BMD; NCCLS, M7-A6, 2003) and E-test. BMD and Etest MICs were analysed on an isolate-per-isolate basis, and MICs within plus or minus one doubling dilution were considered correlative.

Results:  

Against the SA tested, TLV had an MIC range of 0.12–4 mg/L. MICs were similar against both MSSA (0.12–1 mg/L) and MRSA (0.12–1 mg/L). TLV MICs to vancomycin (VAN)-nonsusceptible (NS; intermediate and resistant) SA (n = 4) were 2–4 mg/L and against daptomycin-NS SA (n = 3) were 0.5–2 mg/L. TLV showed MICs against CNS of 0.03–0.5 mg/L with consistent activity against oxacillin-susceptible (S) (0.03–0.5mg/L) and -resistant (R) (0.12–0.25 mg/L) strains. Against VAN-S EF and EM, TLV showed MICs of 0.25–0.5 mg/L and 0.06–0.5 mg/L, respectively and elevated MICs of 0.25–8 mg/L and 4–8 mg/L against VAN-R strains. TLV showed low MICs against all Streptococci (<=0.06 mg/L), including penicillin-R and multidrug-R SP (MICs = 0.015 mg/L). TLV MICs generated using E-test were similar to those generated using BMD. Correlations between E-test and BMD were 84% for SA, 100% for CNS, 100% for EF, 90% for EM, 100% for SP, and 100% for STR.

Conclusions:  

TLV showed potent in vitro activity against the gram-positive organisms tested, including isolates with clinically-relevant resistant phenotypes.