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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.

OrganismNumber (cumulative percentage) of strains inhibited at BC-3205 MIC (mg/L) of:
(no. tested)leqslant R: less-than-or-eq, slant0.030.060.120.250.51248geqslant R: gt-or-equal, slanted16
MSSA (102)2 (2.0)14 (15.7)81 (95.1)5 (100.0)      
MRSA (212)18 (8.5)106 (58.5)88 (100)       
MSCoNS (50)1 (2.0)25 (52.0)21 (94.0)1 (96.0)1 (98.0)1 (100.0)    
MRCoNS (49)3 (5.9)11 (28.6)29 (87.8)6 (100)      
VS-EFM (78)1 (1.3)20 (26.9)18 (50.0)9 (61.5)1 (62.8)1 (64.1)1 (65.4)6 (73.1)3 (76.9)18 (100.0)
VR-EFM (34)1(2.9)13 (41.2)10 (70.6)5 (85.3)1 (88.2)1 (88.2)1 (88.2)2 (94.1)2 (94.1)2 (100.0)
BHS (202)99 (49.0)98 (97.5)5 (100.0)       
VGS (100)37 (37.0)41 (78.0)16 (94.0)4 (98.0)2 (100.0)     

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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