TABLE 4.

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

Enzyme	Drug	Hydrolysis parameter valuea			IC50a (μM)
		kcat (s−1)	Km (μM)	kcat/Km (M−1·s−1)
TEM-3		0.86	160	5,400	4.6
SHV-2		Not determined			3.4
SHV-4		0.42, 0.046b	600, 320	710, 140	4.3
KPC-2	BAL30072	0.055	1,700	32	>2,500
KPC-2	Aztreonam	51	530	97,000	>2,500
IMP-1	BAL30072	Not determined		<0.0001	>2,500
IMP-1	Aztreonam	Not determined		0.002	1100
VIM-1	BAL30072	Not determined		<0.0001	>2,500
E. coli AmpC	BAL30072	0.004	100	38	0.5
E. coli AmpC	Aztreonam	0.00006	21	2.9	0.06
C. freundii AmpC	BAL30072	Not determined	Not determined	Not determined	2.7
P. aeruginosa 18S/H class C	BAL30072	Not determined	Not determined	Not determined	28
P. aeruginosa 143724R class C	BAL30072	Not determined	Not determined	Not determined	27
E. coli PBP 1a	BAL30072	Not determined	Not determined	Not determined	3.9
E. coli PBP 1a	Aztreonam	Not determined	Not determined	Not determined	>50
E. coli PBP 1b	BAL30072	Not determined	Not determined	Not determined	1.9
E. coli PBP 1b	Aztreonam	Not determined	Not determined	Not determined	>50
E. coli PBP 2	BAL30072	Not determined	Not determined	Not determined	30
E. coli PBP 2	Aztreonam	Not determined	Not determined	Not determined	>50
E. coli PBP 3	BAL30072	Not determined	Not determined	Not determined	0.048
E. coli PBP 3	Aztreonam	Not determined	Not determined	Not determined	0.023

^aErrors in the kinetic parameters were less than 20% of the value indicated.

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