Research from E. Cambau and co-researchers in the area of pneumonia described
February 23rd, 2009
2009 FEB 23 -- Researchers detail in 'Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli,' new data in pneumonia. According to recent research published in the Journal of Antimicrobial Chemotherapy, "Besifloxacin is a new fluoroquinolone in development for ocular use. We investigated its mode of action and resistance in two major ocular pathogens, Streptococcus pneumoniae and Staphylococcus aureus, and in the reference species Escherichia coli."
"Primary and secondary targets of besifloxacin were evaluated by: (i) mutant selection experiments; (ii) MIC testing of defined topoisomerase mutants; and (iii) inhibition and cleavable complex assays with purified S. pneumoniae and E. coli DNA gyrase and topoisomerase IV enzymes. Enzyme assays showed similar besifloxacin activity against S. pneumoniae gyrase and topoisomerase IV, with IC(50) and CC(25) of 2.5 and 1 microM, respectively. In contrast to ciprofloxacin and moxifloxacin, besifloxacin was equally potent against both S. pneumoniae and E. coli gyrases. DNA gyrase was the primary target in all three species, with substitutions observed at positions 81, 83 and 87 in GyrA and 426 and 466 in GyrB (E. coli numbering). Topoisomerase IV was the secondary target. Notably, resistant mutants were not recovered at 4-fold besifloxacin MICs for S. aureus and S. pneumoniae, and S. aureus topoisomerase mutants were only obtained after serial passage in liquid medium. Besifloxacin MICs were similarly affected by parC or gyrA mutations in S. aureus and S. pneumoniae and remained below 1 mg/L in gyrA-parC double mutants," wrote E. Cambau and colleagues, .
The researchers concluded: "Although mutant selection experiments indicated that gyrase is a primary target, further biochemical and genetic studies showed that besifloxacin has potent, relatively balanced activity against both essential DNA gyrase and topoisomerase IV targets in S. aureus and S. pneumoniae."
Cambau and colleagues published their study in the Journal of Antimicrobial Chemotherapy (Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. Journal of Antimicrobial Chemotherapy, 2009;63(3):443-50).
For additional information, contact E. Cambau, Universite Paris12, Creteil, France.
The publisher's contact information for the Journal of Antimicrobial Chemotherapy is: Oxford University Press, Great Clarendon St., Oxford OX2 6DP, England.
Keywords: France, Creteil, Anti-Infectives, Antimicrobial Resistance, Antimicrobials, Chemotherapy, Ciprofloxacin, DNA, Drug Resistance, Drug Therapy, Drugs, Enzyme Research, Enzymes, Enzymology, Escherichia coli, Gyrase, Infectious Disease, Moxifloxacin, Pharmaceuticals, Pneumonia, Proteins, Proteomics, Pulmonology, Strep Infection, Streptococcal, Streptococcus, Therapy, Topoisomerase, Topoisomerase I, Treatment.
This article was prepared by Anti-Infectives Week editors from staff and other reports. Copyright 2009, Anti-Infectives Week via NewsRx.com.
