title: Effect of Susceptibility Testing Conditions on the In Vitro Antibacterial Activity of ETX0914.
abstract: The effect of various conditions including pH, inoculum, temperature, atmosphere, divalent cations, and several body fluids on the in vitro activity of the novel antibacterial spiropyrimidinetrione ETX0914 in standard susceptibility tests was investigated against several species. None of the parameters investigated affected the activity of ETX0914, with the exception of pH. Whereas the MIC values for ETX0914 with S. aureus, E. faecalis, and E. coli did not change when the pH of the growth medium was varied from 5 to 8, they did increase at least 8-fold at pH values above 8. This loss of activity can be attributed to the deprotonation of the molecule at elevated pH. The data suggest that routine susceptibility testing with ETX0914 should result in reproducible MIC values.
authors.affiliation: AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA, 02451, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Giacobbe
authors.affiliation: AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA, 02451, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Huband
authors.affiliation: AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA, 02451, USA. Electronic address: Boudewijn.deJonge@astrazeneca.com.
authors.forename: Boudewijn L M
authors.initials: BL
authors.lastname: deJonge
authors.affiliation: AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA, 02451, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001463:Barbiturates / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007555:Isoxazoles; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009025:Morpholines; D023303:Oxazolidinones; D015203:Reproducibility of Results; D013141:Spiro Compounds / Q000494:pharmacology*; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D001463:Barbiturates; D003470:Culture Media; D007555:Isoxazoles; D009025:Morpholines; D023303:Oxazolidinones; D013141:Spiro Compounds; C000599190:zoliflodacin
keywords: ETX0914; Spiropyrimidinetrione; Susceptibility testing