TABLE 4.

Enzymatic parameters for the reaction of BAL30072 with penicillin-binding proteins and β-lactamases

EnzymeDrugHydrolysis parameter valueaIC50a (μM)
kcat (s−1)Km (μM)kcat/Km (M−1·s−1)
TEM-30.861605,4004.6
SHV-2Not determined3.4
SHV-40.42, 0.046b600, 320710, 1404.3
KPC-2BAL300720.0551,70032>2,500
KPC-2Aztreonam5153097,000>2,500
IMP-1BAL30072Not determined<0.0001>2,500
IMP-1AztreonamNot determined0.0021100
VIM-1BAL30072Not determined<0.0001>2,500
E. coli AmpCBAL300720.004100380.5
E. coli AmpCAztreonam0.00006212.90.06
C. freundii AmpCBAL30072Not determinedNot determinedNot determined2.7
P. aeruginosa 18S/H class CBAL30072Not determinedNot determinedNot determined28
P. aeruginosa 143724R class CBAL30072Not determinedNot determinedNot determined27
E. coli PBP 1aBAL30072Not determinedNot determinedNot determined3.9
E. coli PBP 1aAztreonamNot determinedNot determinedNot determined>50
E. coli PBP 1bBAL30072Not determinedNot determinedNot determined1.9
E. coli PBP 1bAztreonamNot determinedNot determinedNot determined>50
E. coli PBP 2BAL30072Not determinedNot determinedNot determined30
E. coli PBP 2AztreonamNot determinedNot determinedNot determined>50
E. coli PBP 3BAL30072Not determinedNot determinedNot determined0.048
E. coli PBP 3AztreonamNot determinedNot determinedNot determined0.023
  • a Errors in the kinetic parameters were less than 20% of the value indicated.

  • b The reaction progress curves were strongly biphasic; the parameters are given for the initial burst and the continuing steady-state rate of hydrolysis.