Update on Telavancin Activity Tested Against a Global Collection of Gram-positive Pathogens (2010)

Telavancin-susceptible breakpoints for S. aureus (≤1 µg/mL), vancomycin-susceptible E. faecalis (≤1 µg/mL), BHS ( ≤0.12 µg/mL), and VGS (≤0.12 µg/mL) were those approved by the US Food and Drug Administration (FDA). 2 • Enterococcal isolates were clustered according to glycopeptide susceptibility. The VanA phenotype was characterized by non-susceptibility to vancomycin ( ≥8 µg/mL) and teicoplanin ( ≥16 µg/mL), while isolates with a VanB phenotype were those nonsusceptible to vancomycin ( ≥8 µg/mL), but susceptible to teicoplanin ( ≤8 µg/mL), according to the CLSI interpretive criteria. 4 RESULTS • Resistance to oxacillin was observed in 40.4% and 74.0% of S. aureus and CoNS, respectively. Telavancin (MIC 50/90 , 0.12/0.25 µg/mL) exhibited equivalent potencies when tested against S. aureus and CoNS and inhibited all isolates at ≤1 µg/mL, regardless of oxacillin resistance ( Table 1 ). • When tested against MRSA, telavancin (MIC 50/90 , 0.12/0.25 µg/mL) was 2-fold more potent than daptomycin (MIC 50/90 , 0.25/0.5 µg/mL) and 4- to 8-fold more active than vancomycin (MIC 50/90 , 1/1 µg/mL) and linezolid (MIC 50/90 , 1/1 µg/mL; Table 2 ). • When tested against a worldwide collection of CoNS, telavancin (MIC 50/90 , 0.12/0.25 µg/mL) was 2-fold more potent than daptomycin (MIC 50/90 , 0.25/0.5 µg/mL) and 4- to 8-fold more active than linezolid (MIC 50/90 , 0.5/1 µg/mL) and vancomycin (MIC 50/90 , 1/2 µg/mL; Table 2 ). • When tested against E. faecalis , telavancin (MIC 50/90 , 0.5/0.5 µg/mL) inhibited 97.8% of clinical isolates at ≤1 µg/mL, including 6 VanB-type strains. All 32 E. faecalis exhibiting telavancin MIC at ≥2 µg/mL displayed a VanA phenotype ( Table 1 ). • When tested against all E. faecalis , telavancin (MIC 50/90 , 0.5/0.5 µg/mL) demonstrated MIC 90 values 2- to 4-fold lower than ampicillin (MIC 50/90 , ≤1/2 µg/mL), vancomycin (MIC 50/90 , 1/2 µg/mL), daptomycin (MIC 50/90 , 1/1 µg/mL), and linezolid (MIC 50/90 , 1/2 µg/mL; Table 2 ). • Telavancin tested against vancomycin-susceptible E. faecium (MIC 50/90 , 0.06/0.12 µg/mL) was 4- to 8-fold more active when compared with vancomycin-susceptible E. faecalis (MIC 50/90 , 0.5/0.5 µg/mL; Table 1 ). • When tested against vancomycin-susceptible E. faecium , telavancin (MIC 50/90 , 0.06/0.12 µg/mL) was 8- to 16-fold more active than vancomycin (MIC 50/90 , 1/1 µg/mL) and 16- to 32-fold more active than daptomycin (MIC 50/90 , 2/2 µg/mL; Table 2 ). • VanB-type E. faecium (MIC 50/90 , 0.12/0.5 µg/mL) exhibited higher telavancin MIC values when compared with vancomycin-susceptible strains (MIC 50/90 , 0.06/0.12 µg/mL; Table 1 ), yet telavancin inhibited all strains at ≤1 µg/mL. VanA-type E. faecium showed decreased susceptibility to telavancin (MI C50/90 , 2/>2 µg/mL). • Telavancin (MIC 50/90 , ≤0.015/0.03 µg/mL) was very potent against S. pneumoniae isolates, from which 0.6% and 22.4% of S. pneumoniae were penicillin-resistant using the CLSI criteria (parenteral [ ≥8 µg/mL] and oral [ ≥2 µg/mL] therapy breakpoints, respectively; Table 2 ). • Telavancin MIC 50 results when tested against BHS serogroup B (MIC 50/90 , 0.06/0.12 µg/mL) were slightly higher (2-fold) than those noted against serogroup A (MIC 50/90 , 0.03/0.06 µg/mL), serogroup C (MIC 50/90 , 0.03/0.06 µg/mL), serogroup F (MIC 50 , 0.03 µg/mL), and serogroup G (MIC 50/90 , 0.03/0.12 µg/mL; Table 1 ). • Among VGS, 5.4% of strains were fully resistant to penicillin ( Table 2 ). Telavancin (MIC 50/90 , 0.03/0.06 µg/mL) was 2- to 16-fold more potent than penicillin (MIC 50/90 , 0.06/1 µg/mL), daptomycin (MIC 50/90 , 0.25/0.5 µg/mL), vancomycin (MIC 50/90 , 0.5/0.5 µg/mL), and linezolid (MIC 50/90 , 1/1 µg/mL) when tested against VGS. Table 1. Antimicrobial activity of telavancin tested against a worldwide collection of Gram-positive clinical isolates (2010) Organism/groups MIC ( µg/mL) Number (cumulative %) of isolates inhibited at each telavancin MIC ( µg/mL) of: