Table 1.

Meropenem Time-Kill Results Against Klebsiella pneumoniae That Developed Ceftazidime-Avibactam Resistance^a

Isolate	ST	KPC Variant	MIC (µg/mL)b			Log-Kill at 24 Hours in Presence of Meropenemc
			Ceftazidime-Avibactam	Ceftazidime	Meropenem	4× MIC	8× MIC	16 µg/mL
1-A	258	KPC-3	2 (S)	512	128	d	d	+3.53
1-B	258	D179Y, T243M	256	>512	0.5 (S)	−4.97	−4.27	−4.97
1-C	258	D179Y, T243M	256	>512	0.25 (S)	−5.94	−4.94	−5.96
2-A	258	KPC-3	4 (S)	256	32	d	d	+3.57
2-B	258	V240G	32	>512	8	−6.14	−6.14	−6.14
2-C	258	D179Y	>256	>512	4	−4.64	−5.64	−4.64
3-A	258	KPC-3	2 (S)	256	32	d	d	+3.52
3-B	258	D179Y	128	512	0.25 (S)	−5.98	−5.98	−5.98
3-C	258	D179Y	64	512	0.125 (S)	−3.18	−3.18	−5.83
4-A	258	KPC-3	1 (S)	256	16	d	d	+3.52
4-B	258	A177E, D179Y	256	256	0.25 (S)	−3.70	−5.16	−6.16
4-C	258	A177E, D179Y	128	256	0.25 (S)	−3.26	−2.54	−5.96

Abbreviations: cfu, colony-forming units; CLSI, Clinical Laboratory Standards Institute; KPC, Klebsiella pneumoniae carbapenemase; MIC, minimum inhibitory concentration; S, susceptible based on CLSI interpretive criteria; ST, sequence type. Bolded rows represent the baseline isolate from each of the 4 patients.

^aTime-kill assays were performed in duplicate for each isolate, using a 1 × 10⁶ cfu/mL inoculum in cation-adjusted Mueller-Hinton broth. Bactericidal responses were defined as a ≥3-log decrease in cfu/mL from the starting inoculum at 24 hours.

^bMICs were determined by broth microdilution according to reference methods (1). CLSI interpretative criteria were applied to define susceptibility as follows: ceftazidime-avibactam, ≤8 µg/mL; ceftazidime, ≤4 µg/mL; meropenem, ≤1 µg/mL.

^cDifference in concentration (log₁₀) compared with baseline (time 0). Data are shown for a representative replicate of each isolate.

^dNot tested.