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Antimicrob Agents Chemother. 2002 Oct;46(10):3168-74.
In vitro antimicrobial activity of GSQ1530, a new heteroaromatic polycyclic compound.

Ge Y, Difuntorum S, Touami S, Critchley I, Burli R, Jiang V, Drazan K, Moser H.

Genesoft Inc., South San Francisco, California 94080, USA. jgenesoft.com

GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were coevaluated against 215 clinical isolates. The MICs at which 90% of isolates are inhibited (MIC(90)s) of GSQ1530 for methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were 2 and 4 micro g/ml, respectively. The MIC(90)s of GSQ1530 for the streptococci tested were 2 micro g/ml or less, regardless of their susceptibilities to other antibiotics. The MIC(90) of GSQ1530 for the enterococci tested (including vancomycin-resistant enterococci) was 4 micro g/ml. No cross-resistance was found between GSQ1530 and other known antibiotics. In a separate assay, GSQ1530 demonstrated excellent activity against vancomycin-intermediate-susceptible staphylococci (MIC(90), 1 micro g/ml). The minimal bactericidal concentration test was conducted with 73 clinical isolates; GSQ1530 was cidal against streptococci and staphylococci but static against enterococci. An in vitro killing kinetic study revealed a time-dependent profile, with at least a 3-log reduction of bacterial growth within 6 h after exposure to four times the MICs of GSQ1530 for both S. aureus and Streptococcus pneumoniae. The checkerboard study showed that GSQ1530 had a synergistic interaction with rifampin against MRSA. The test medium was found to have little effect on in vitro antimicrobial potency. The MICs of GSQ1530 for gram-positive cocci were 4- to 32-fold higher in the presence of serum proteins. GSQ1530 has high levels of plasma protein binding (91 and 89% for rat and human plasma, respectively). These preliminary results demonstrate that GSQ1530, a representative compound of our novel HARP antibiotics, has broad-spectrum activity against gram-positive bacteria. This novel class of antibacterial compounds is profiled in vivo to assess the therapeutic potential in humans. Ongoing in vivo studies will assess whether this class of molecules has promising in vivo efficacy and safety profiles.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234840&dopt=Abstract












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