Literature DB >> 14973152

In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698.

Denene Lofland1, Stacey Difuntorum, Andrew Waller, John M Clements, Mellany K Weaver, James A Karlowsky, Kirk Johnson.   

Abstract

OBJECTIVES: BB-83698 is a peptide deformylase inhibitor currently in clinical trials in Europe. The purpose of this study was to provide additional susceptibility data from clinical isolates, including drug-resistant strains.
METHODS: The in vitro activities of BB-83698 and comparators were determined against 281 streptococci, 154 Staphylococcus aureus, 110 Haemophilus influenzae and 50 Moraxella catarrhalis strains selected for their resistance phenotypes. Broth microdilution MICs and MBCs were determined according to NCCLS guidelines.
RESULTS: The MIC90s were 0.25-0.5 mg/L for S. pneumoniae, including penicillin-, erythromycin-, levofloxacin- and multidrug-resistant strains. The MIC90s for Streptococcus pyogenes and Streptococcus agalactiae were 0.12 mg/L and for viridans streptococci, the MIC90 was 0.5 mg/L. Against S. aureus, including oxacillin- and levofloxacin-resistant strains, and vancomycin-intermediate strains, the MIC90 was 8 mg/L. Against beta-lactamase-negative and -positive H. influenzae, the MIC90s were 32 and 64 mg/L, respectively, and against both beta-lactamase-negative and -positive M. catarrhalis the MIC90 was 0.12 mg/L. In MBC studies, the ratio of MBC/MIC was 1:1 or 2:1 against 31% of S. pneumoniae, 33% of S. aureus, 63% of H. influenzae and 9% of M. catarrhalis.
CONCLUSIONS: Although BB-83698 has reduced in vitro activity against H. influenzae, it is a potent antimicrobial with excellent activity against streptococci and Moraxella.

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Year:  2004        PMID: 14973152     DOI: 10.1093/jac/dkh129

Source DB:  PubMed          Journal:  J Antimicrob Chemother        ISSN: 0305-7453            Impact factor:   5.790


  15 in total

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Journal:  Antimicrob Agents Chemother       Date:  2004-12       Impact factor: 5.191

2.  Phylogenomic and biochemical characterization of three Legionella pneumophila polypeptide deformylases.

Authors:  Jianzhong Huang; Glenn S Van Aller; Amy N Taylor; John J Kerrigan; Wu-Schyong Liu; Janice M Trulli; Zhihong Lai; David Holmes; Kelly M Aubart; James R Brown; Magdalena Zalacain
Journal:  J Bacteriol       Date:  2006-07       Impact factor: 3.490

3.  Pharmacokinetics/Pharmacodynamics of Peptide Deformylase Inhibitor GSK1322322 against Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Rodent Models of Infection.

Authors:  Jennifer Hoover; Thomas Lewandowski; Robert J Straub; Steven J Novick; Peter DeMarsh; Kelly Aubart; Stephen Rittenhouse; Magdalena Zalacain
Journal:  Antimicrob Agents Chemother       Date:  2015-10-19       Impact factor: 5.191

4.  Frequency of Spontaneous Resistance to Peptide Deformylase Inhibitor GSK1322322 in Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae.

Authors:  Sharon Min; Karen Ingraham; Jianzhong Huang; Lynn McCloskey; Sarah Rilling; Anne Windau; Jason Pizzollo; Deborah Butler; Kelly Aubart; Linda A Miller; Magdalena Zalacain; David J Holmes; Karen O'Dwyer
Journal:  Antimicrob Agents Chemother       Date:  2015-05-26       Impact factor: 5.191

5.  Prediction of Pharmacokinetics of IDP-73152 in Humans Using Physiologically-Based Pharmacokinetics.

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Journal:  J Mol Biol       Date:  2009-02-21       Impact factor: 5.469

7.  Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor, GSK1322322.

Authors:  Karen O'Dwyer; Meredith Hackel; Sarah Hightower; Daryl Hoban; Samuel Bouchillon; Donghui Qin; Kelly Aubart; Magdalena Zalacain; Deborah Butler
Journal:  Antimicrob Agents Chemother       Date:  2013-03-11       Impact factor: 5.191

8.  Potent sub-MIC effect of GSK1322322 and other peptide deformylase inhibitors on in vitro growth of Staphylococcus aureus.

Authors:  Deborah Butler; Dongzhao Chen; Karen O'Dwyer; Thomas Lewandowski; Kelly Aubart; Magdalena Zalacain
Journal:  Antimicrob Agents Chemother       Date:  2013-10-28       Impact factor: 5.191

9.  Comparative QSAR studies on peptide deformylase inhibitors.

Authors:  Ji Young Lee; Munikumar Reddy Doddareddy; Yong Seo Cho; Hyunah Choo; Hun Yeong Koh; Jae-Hoon Kang; Kyoung Tai No; Ae Nim Pae
Journal:  J Mol Model       Date:  2007-02-27       Impact factor: 2.172

10.  Drug forecast - the peptide deformylase inhibitors as antibacterial agents.

Authors:  David R P Guay
Journal:  Ther Clin Risk Manag       Date:  2007-08       Impact factor: 2.423

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