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Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections.

ABSTRACT: BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC(50/90), 0.12/0.25 ?g/ml), coagulase-negative staphylococci (MIC(50/90), 0.06/0.12 ?g/ml), ?-hemolytic streptococci (MIC(50/90), 0.03/0.06 ?g/ml), viridans group streptococci (MIC(50/90), 0.12/0.5 ?g/ml), and Enterococcus faecium (including vancomycin-nonsusceptible strains) (MIC(50/90), 0.12/2 ?g/ml). Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes.

SUBMITTER: Sader HS

PROVIDER: S-EPMC3294907 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections.

Sader Helio S HS Biedenbach Douglas J DJ Paukner Susanne S Ivezic-Schoenfeld Zrinka Z Jones Ronald N RN

Antimicrobial agents and chemotherapy 20120109 3

BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC(50/90), 0.12/0.25 μg/ml), coagulase-nega ...[more]

PMID: 22232289

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Project description:The activities of the novel β-lactam-β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli-8,640 Enterobacteriaceae, 1,967 Pseudomonas aeruginosa, and 321 Acinetobacter sp. isolates-were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% of Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli and Klebsiella pneumoniae, meropenem-nonsusceptible (MIC≥2 μg/ml) K. pneumoniae, and ceftazidime-nonsusceptible Enterobacter cloacae. Among ESBL-phenotype K. pneumoniae strains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Among P. aeruginosa strains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptible P. aeruginosa (MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml). Acinetobacter spp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such as K. pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and meropenem-nonsusceptible P. aeruginosa.

Dataset Information

Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections.

Publications

Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections.

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