TABLE 3.

Activities of cefepime-enmetazobactam and comparator agents tested against clinical Gram-negative isolates

Species (n), drug, and region	MIC (μg/ml)			% susceptible
	MIC50	MIC90	Range	CLSI	EUCAST
Enterobacteriaceae
All (1,696)
Cefepime	0.06	32	0.015 to >64	83.7	82.5
Cefepime-enmetazobactam	0.06	0.25	0.015 to >64	NAc	NA
Piperacillin-tazobactam	2	64	0.12 to >128	85.7	82.0
Meropenem	0.03	0.06	0.008 to >8	96.2	96.4
Ceftolozane-tazobactam	0.25	2	0.06 to >32	90.7	88.5
Ceftazidime	0.25	64	0.03 to >64	81.2	77.7
Ceftazidime-avibactam	0.12	0.5	≤0.015 to >64	99.7	99.7
Gentamicin	0.5	16	0.12 to >32	89.0	88.3
Ciprofloxacin	0.03	>16	0.004 to >16	71.7	71.7
United States (848)
Cefepime	0.06	4	0.015 to >64	88.6	87.9
Cefepime-enmetazobactam	0.06	0.25	0.015 to >64	NA	NA
Piperacillin-tazobactam	2	32	0.12 to >128	89.5	86.2
Meropenem	0.03	0.03	0.008 to >8	97.8	97.8
Ceftolozane-tazobactam	0.25	1	0.06 to >32	93.8	91.4
Ceftazidime	0.25	32	0.03 to >64	86.1	83.4
Ceftazidime-avibactam	0.12	0.25	≤0.015 to 16	99.9	99.9
Gentamicin	0.5	2	0.12 to >32	90.9	90.3
Ciprofloxacin	0.03	>16	0.004 to >16	75.4	75.4
Europe (848)
Cefepime	0.06	>64	0.015 to >64	78.9	77.1
Cefepime-enmetazobactam	0.06	0.25	0.015 to >64	NA	NA
Piperacillin-tazobactam	2	>128	0.25 to >128	81.8	77.8
Meropenem	0.03	0.06	0.008 to >8	94.7	95.0
Ceftolozane-tazobactam	0.25	4	0.06 to >32	87.6	85.6
Ceftazidime	0.25	64	0.06 to >64	76.3	71.9
Ceftazidime-avibactam	0.12	0.5	≤0.015 to >64	99.5	99.5
Gentamicin	0.5	32	0.12 to >32	87.1	86.3
Ciprofloxacin	0.03	>16	0.004 to >16	68.0	68.0
E. coli (697)
Cefepime	0.06	16	0.015 to >64	85.8	84.4
Cefepime-enmetazobactam	0.06	0.12	0.015 to 32	NA	NA
Piperacillin-tazobactam	2	8	≤0.12 to >128	92.4	90.5
Meropenem	0.015	0.03	0.008 to 8	99.6	99.7
Ceftolozane-tazobactam	0.25	0.5	0.06 to >32	98.1	96.8
Ceftazidime	0.25	16	0.06 to >64	86.7	82.2
Ceftazidime-avibactam	0.12	0.25	≤0.015 to 2	100	100
Gentamicin	0.5	32	0.12 to >32	86.2	85.5
Ciprofloxacin	0.015	>16	0.004 to >16	64.1	64.1
E. coli ESBL genotypea (109)
Cefepime	16	>64	0.12 to >64	13.8	6.4
Cefepime-enmetazobactam	0.06	0.12	0.016 to 32	NA	NA
Piperacillin-tazobactam	4	64	0.5 to >128	82.6	75.2
Meropenem	0.03	0.03	0.008 to 8	99.1	99.1
Ceftolozane-tazobactam	0.5	2	0.12 to >32	93.6	88.1
Ceftazidime	16	64	1 to >64	26.6	3.7
Ceftazidime-avibactam	0.12	0.25	≤0.015 to 2	100	100
Gentamicin	1	>32	0.12 to >32	59.6	58.7
Ciprofloxacin	>16	>16	0.008 to >16	9.2	9.2
K. pneumoniae (799)
Cefepime	0.06	>64	0.015 to >64	80.9	80.6
Cefepime-enmetazobactam	0.06	0.5	0.015 to >64	NA	NA
Piperacillin-tazobactam	4	>128	0.25 to >128	83.1	78.6
Meropenem	0.03	0.12	0.008 to >8	92.7	92.9
Ceftolozane-tazobactam	0.25	8	0.06 to >32	87.5	85.7
Ceftazidime	0.25	>64	0.03 to >64	80.4	78.1
Ceftazidime-avibactam	0.12	0.5	≤0.015 to >64	99.6	99.6
Gentamicin	0.25	8	0.12 to >32	90.0	89.1
Ciprofloxacin	0.03	>16	0.004 to >16	75.2	75.2
K. pneumoniae ESBL genotypea (102)
Cefepime	64	>64	1 to >64	3.9	2.0
Cefepime-enmetazobactam	0.12	1	0.03 to 8	NA	NA
Piperacillin-tazobactam	32	>128	1 to >128	44.1	28.4
Meropenem	0.03	1	0.016 to >8	92.2	91.2
Ceftolozane-tazobactam	2	32	0.12 to >32	52.9	47.1
Ceftazidime	64	>64	0.25 to >64	4.9	2.0
Ceftazidime-avibactam	0.25	1	≤0.015 to 2	100	100
Gentamicin	32	>32	0.25 to >32	41.2	38.2
Ciprofloxacin	>16	>16	0.008 to >16	7.8	7.8
K. pneumoniae KPC genotypeb (45)
Cefepime	>64	>64	8 to >64	0.0	0.0
Cefepime-enmetazobactam	16	>64	0.5 to >64	NA	NA
Piperacillin-tazobactam	>128	>128	1 to >128	2.2	2.2
Meropenem	>8	>8	4 to >8	0.0	0.0
Ceftolozane-tazobactam	>32	>32	16 to >32	0.0	0.0
Ceftazidime	>64	>64	32 to >64	0.0	0.0
Ceftazidime-avibactam	1	4	0.03 to >16	97.8	97.8
Gentamicin	2	>32	0.12 to >32	71.1	66.7
Ciprofloxacin	>16	>16	0.5 to >16	0.0	0.0
E. aerogenes (100)
Cefepime	0.06	0.5	0.015 to 8	97.0	96.0
Cefepime-enmetazobactam	0.06	0.25	0.015 to 2	NA	NA
Piperacillin-tazobactam	2	64	0.25 to 128	77.0	69.0
Meropenem	0.03	0.12	0.015 to 1	100	100
Ceftolozane-tazobactam	0.25	4	0.06 to 32	84.0	76.0
Ceftazidime	0.25	64	0.06 to >64	73.0	65.0
Ceftazidime-avibactam	0.12	0.5	≤0.015 to 4	100	100
Gentamicin	0.5	0.5	0.12 to >32	98.0	98.0
Ciprofloxacin	0.015	0.12	0.004 to >16	91.0	91.0
E. cloacae (100)
Cefepime	0.12	16	0.03 to >64	79.0	71.0
Cefepime-enmetazobactam	0.12	1	0.03 to >64	NA	NA
Piperacillin-tazobactam	4	128	1 to >128	68.0	63.0
Meropenem	0.03	0.12	0.008 to >8	97.0	98.0
Ceftolozane-tazobactam	0.5	16	0.25 to >32	71.0	65.0
Ceftazidime	0.5	>64	0.12 to >64	58.0	55.0
Ceftazidime-avibactam	0.25	0.5	0.03 to >64	98.0	98.0
Gentamicin	0.25	0.5	0.12 to >32	92.0	92.0
Ciprofloxacin	0.03	2	0.008 to >16	77.0	77.0
P. aeruginosa (297)
Cefepime	4	16	0.12 to >64	79.5	79.5
Cefepime-enmetazobactam	4	16	0.12 to >64	NA	NA
Piperacillin-tazobactam	8	128	0.12 to >128	75.4	75.4
Meropenem	0.5	>8	0.015 to >8	76.4	76.4
Ceftolozane-tazobactam	0.5	4	0.25 to >32	92.6	92.6
Ceftazidime	4	64	0.25 to >64	78.5	78.5
Ceftazidime-avibactam	2	8	0.06 to >64	95.0	95.0
Gentamicin	2	32	0.12 to >32	84.5	84.5
Ciprofloxacin	0.25	16	0.004 to >16	68.0	68.0
United States (149)
Cefepime	4	16	0.5 to >64	82.6	82.6
Cefepime-enmetazobactam	4	16	0.12 to >64	NA	NA
Piperacillin-tazobactam	4	64	0.12 to >128	81.2	81.2
Meropenem	0.5	8	0.015 to >8	75.2	75.2
Ceftolozane-tazobactam	0.5	2	0.25 to >32	98.0	98.0
Ceftazidime	4	16	0.5 to 64	87.2	87.2
Ceftazidime-avibactam	2	4	0.25 to >64	98.7	98.7
Gentamicin	2	8	0.12 to >32	89.3	89.3
Ciprofloxacin	0.12	8	0.03 to >16	73.2	73.2
Europe (148)
Cefepime	4	32	0.12 to >64	76.4	76.4
Cefepime-enmetazobactam	4	32	0.12 to >64	NA	NA
Piperacillin-tazobactam	8	>128	0.25 to >128	69.9	69.9
Meropenem	0.5	>8	0.03 to >8	77.7	77.7
Ceftolozane-tazobactam	0.5	8	0.25 to >32	87.2	87.2
Ceftazidime	4	64	0.25 to >64	69.6	69.6
Ceftazidime-avibactam	2	8	0.06 to >64	91.2	91.2
Gentamicin	2	>32	0.12 to >32	79.6	79.6
Ciprofloxacin	0.25	>16	0.004 to >16	62.8	62.8

^aIsolates containing genes encoding an ESBL with or without OXA-48 or AmpC β-lactamases.

^bIsolates containing genes encoding a KPC with or without an ESBL, OXA-48, and/or AmpC β-lactamases.

^cNA, not applicable.