Activity of BC-3205 when tested against Gram-positive organisms responsible from skin and skin structure infections
Abstract number: P911
Objective: To assess the in vitro activity for BC-3205, a novel semi-synthetic pleuromutilin, against a contemporary collection of Gram-positive cocci. Pleuromutilins inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. BC-3205 is in early stage clinical development for oral treatment of multidrug-resistant (R) skin and skin structure infections (SSSI).
Methods: Over 800 unique contemporary clinical isolates of Gram-positive organisms tested for susceptibility (S) by broth microdilution methods (CLSI, M07-A8) to BC-3205 and comparator agents, including azithromycin (AZ), clindamycin (CL) and linezolid (LZ). The organisms tested were S. aureus (SA; 314), coagulase-negative staphylococci (CoNS; 99), E. faecium (EFM; 112), b-haemolytic streptococci (BHS; 202) and viridans group streptococci (VGS; 100). Interpretation of results was guided by CLSI (M100-S19, 2009) and EUCAST criteria.
Results: BC-3205 was very active against SA (MIC50/90, 0.12/0.12 mg/L) and showed similar potency against methicillin-S (MSSA) and -R (MRSA) strains. Against MRSA, BC-3205 (MIC50/90, 0.06/0.12 mg/L) showed significantly greater activity than CL (MIC50/90, 0.12/>16 mg/L), LZ (MIC50/90, 2/2 mg/L) and AZ (MIC50/90, >16/>16 mg/L). Methicillin-S (MSCoNS) and -R CoNS (MRCoNS) were also very S to BC-3205 (see Table). LZ (MIC50/90, 1/1 mg/L) was also very potent against CoNS, but eight- to 16-fold less active than BC-3205. CL and AZ showed more limited activity against CoNS, especially MRCoNS strains (MIC50/90, 0.12/>16 and >16/>16 mg/L, respectively). BC-3205 was highly active against vancomycin-S (VS) and vancomycin-R (VR) EFM (MIC50, 0.12 mg/L for both). BHS strains were very S to BC-3205 (MIC50/90, 0.06/0.06 mg/L). BC-3205 (MIC50/90, 0.06/0.12 mg/L) was four- and 16-fold more active than AZ (MIC50/90, 0.25/8 mg/L) and LZ (MIC50/90, 1/1 mg/L); but slightly less potent than CL (MIC50/90, 0.03/0.12 mg/L), when tested against VGS.
Conclusions: BC-3205 was very active against a representative collection of contemporary pathogens associated with SSSI. Pending further pharmacokinetic/pharmacodynamic and early clinical trial studies, BC-3205 appears to be a promising treatment for cutaneous infections caused by R Gram-positive organisms.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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