Antimicrobial Activity of the Investigational Pleuromutilin Compound BC-3781 Tested against Gram-Positive Organisms Commonly Associated with Acute Bacterial Skin and Skin Structure Infections

Antimicrobial Activity of the Pleuromutilin Antibiotic BC-3781 against Bacterial Pathogens Isolated in the SENTRY Antimicrobial Surveillance Program in 2010

“…BC-3781 MICs were lower among vancomycin-nonsusceptible strains (MIC 50 , 0.06 g/ml, and MIC 90 , 0.25 g/ml) than among vancomycin-susceptible strains (MIC 50 , 0.12 g/ml, and MIC 90 , Ͼ16 g/ml [ Table 2]), as already observed in earlier studies (23). Elevated BC-3781 MICs of Ն2 g/ml were shown against 23.7% of vancomycin-susceptible isolates, but only with 3.0% of vancomycin-nonsusceptible strains.…”

“…Similar to BC-3781, quinupristin-dalfopristin was slightly more active against vancomycin-nonsusceptible E. faecium (MIC 50/90 , Յ0.5/1 g/ml; 97.0% susceptible) than against vancomycin-susceptible E. faecium (MIC 50/90 , Յ0.5/2 g/ml; 76.7% susceptible). BC-3781 was not evaluated against E. faecalis since previous investigations showed no significant activity against this species (23).…”

“…BC-3781 is the first systemic pleuromutilin derivative in development for intravenous and oral administration to combat serious infections in humans. It has completed clinical phase 2 in ABSSSI (18)(19)(20)(21)(22)(23). The spectrum of activity of this new antibacterial comprises of potent activity against organisms commonly isolated from ABSSSI, as well as those causing CABP, including multidrugresistant Gram-positive cocci and those causing atypical pneumonia, such as Mycoplasma pneumoniae (MIC 50/90 , 0.006/0.006 g/ ml), Chlamydophila pneumoniae (MIC 50/90 , 0.02/0.04 g/ml), and Legionella pneumophila (MIC 50/90 , 0.06/0.5 g/ml) (22,23).…”

“…The spectrum of activity of this new antibacterial comprises of potent activity against organisms commonly isolated from ABSSSI, as well as those causing CABP, including multidrugresistant Gram-positive cocci and those causing atypical pneumonia, such as Mycoplasma pneumoniae (MIC 50/90 , 0.006/0.006 g/ ml), Chlamydophila pneumoniae (MIC 50/90 , 0.02/0.04 g/ml), and Legionella pneumophila (MIC 50/90 , 0.06/0.5 g/ml) (22,23). BC-3781 has also been shown to be active against Enterococcus faecium (particularly vancomycin-resistant strains [VRE]), which has become an important nosocomial pathogen, whereas it is not active against Enterococcus faecalis (23).…”

Crystal structure of 14-O-[(2-methylbenzamide-2-methylpropane-2-yl) thioacetate] Mutilin, C38H61NO7S

“…Pleuromutilin was first isolated in acrystalline form from cultures of two species of basidiomycetes, Pleurotus mutilus and P. passeckerianus in 1951 [1].P leuromutilin is a diterpene, constituted of arather rigid 5-6-8tricyclic carbon skeleton with eight stereogenic centers [2,3]. The derivatives of pleuromutilin have received much investigative attention due to the high activities against drug-resistant Gram-positive bacteria and mycoplasmas in vitro and in vivo [4],p harmacodynamic properties [5] and no target-specific cross-resistance to other antibiotics [6]. The crystal structure of the title compound is built up of C 34 H 49 NO 5 S, 2(C 2 H 6 O) moleculescontaininga5-6-8 tricyclic carbon skeleton and abenzene ring, in which all bond lengths are in normalranges.…”