AZD2563, a novel oxazolidinone: definition of antibacterial spectrum, assessment of bactericidal potential and the impact of miscellaneous factors on activity in vitro.
AZD2563, a new oxazolidinone targeted at Gram-positive bacteria, was evaluated and compared with linezolid and other agents against 802 aerobic bacterial isolates for spectrum of activity, bactericidal activity, and the effect of miscellaneous factors upon activity in vitro. At a concentration of 2 mg/L, AZD2563 inhibited 98% of all Gram-positive bacteria tested (100% at 4 mg/L), including susceptible and resistant isolates of Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., Streptococcus pneumoniae, other Streptococcus spp. and Corynebacterium spp. Conversely, all Enterobacteriaceae and non-fermenting Gram-negative bacteria had MICs > 128 mg/L, and only a few Haemophilus or Moraxella spp. had MICs < 8 mg/L. By conventional laboratory definition, AZD2563 and linezolid were bacteriostatic against staphylococci and enterococci, with variable bactericidal activity against Strep. pneumoniae. The in-vitro activity of AZD2563 was essentially unaffected by altering pH, inoculum size, the type of testing medium, or the inclusion of human serum up to 25% v/v.
Wookey
A
A
Antibiotic Development and Technical Support Group, AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK.
Turner
P J
PJ
Greenhalgh
J M
JM
Eastwood
M
M
Clarke
J
J
Sefton
C
C
D001419:Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*
D023303:Oxazolidinones; C453362:posizolid