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Antimicrobial activity of the investigational pleuromutilin compound BC-3781 against Gram-positive organisms commonly associated with cutaneous infections

Abstract number: P910

Objective: To determine the antimicrobial activity of BC-3781 against recent clinical isolates of Gram-positive cocci. BC-3781 is an investigational semi-synthetic pleuromutilin derivative, which inhibits ribosomal protein synthesis. BC-3781 binds to 50S ribosomal subunit and cross resistance with other antimicrobial classes is very uncommon.

Methods: Antimicrobial activity of BC-3718 and comparator agents was determined against 827 non-duplicate Gram-positive organisms, including staphylococci (413), streptococci (302) and enterococci (112). Susceptibility (S) testing used the CLSI reference broth microdilution method (M07-A8, 2009) for MIC determinations with BC-3781 and comparator drugs (azithromycin [AZ], clindamycin [CL] and linezolid [LZ]). Interpretation of MIC values were based on CLSI (M100-S19, 2009) and EUCAST (2009) S criteria.

Results: Staphylococcal isolates were very S to BC-3781 with highest MIC value being 0.25 and 1 mg/L for S. aureus (SA) and coagulase-negative staphylococci (CoNS), respectively. BC-3781 was eight- to 16-fold more potent than LZ and also showed greater potency compared to AZ and CL when tested against staphylococci (Table). Methicillin-S and -resistant (R) staphylococci showed similar BC-3781 MIC distributions. Highest BC-3781 MIC value among b-haemolytic streptococci (BHS) was 0.12 mg/L. BC-3781 was slightly more active than CL and eight- to 16-fold more active than LZ when tested against BHS. Viridans group streptococci (VGS) was also BC-3781-S, but MIC values were slightly elevated compared to BHS. BC-3781 showed potent activity against vancomycin-S and -R E. faecium (EFM), and it was significantly more active than comparators against EFM. However, 28.6% of EFM exhibited higher (geqslant R: gt-or-equal, slanted2 mg/L) BC-3781 MIC values (mechanism unknown).

Conclusions: BC-3781 was very active against a contemporary (2008–2009) collection of staphylococci, streptococci and enterococci, organisms commonly associated with cutaneous infections. BC-3781 activity was not adversely influenced by R to methicillin among staphylococci or vancomycin among enterococci. Further studies are warrant to determine the role of this novel pleuromutilin for the treatment skin and skin structure infections.

Table. Activity of BC-3781 and comparator agents tested against selected Gram-positive cocci

OrganismBC-3781AzithromycinClindamycinLinezolid
(no. tested)MIC50/90%SaMIC50/90%SaMIC50/90%SaMIC50/90%Sa
SA (314)0.12/0.12100.0a16/>1634.10.12/>1677.12/2100.0
CoNS (99)0.06/0.12100.0a>16/>1647.50.12/>1676.81/199.0
BHS (202)0.03/0.06100.0a0.12/884.70.06/0.1294.11/1100.0
VGS (100)0.12/0.598.0a0.25/8a0.03/0.1291.01/1a
EFM (112)0.12/1671.4a>16/>16a>16/>16a2/297.3
aAn ECV of leqslant R: less-than-or-eq, slant1 mg/L was applied for comparison purposes only; breakpoint criteria published by EUCAST; and - = no breakpoint has been established.

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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