Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens

J. A. Sutcliffe; W. O'Brien; C. Fyfe; T. H. Grossman

doi:10.1128/AAC.01288-13

DOI: 10.1128/AAC.01288-13

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Fig 1
Chemical structure of eravacycline (TP-434).

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Table 1

Susceptibilities of Gram-negative aerobic bacteria to eravacycline and comparators^{^a}

Organism	MIC_50/90 (μg/ml), MIC range (μg/ml), and no. of isolates
Organism	ERV	TET	TGC	CARB	AG	3rd GC	FQ	CST	PTZ
Acinetobacter baumannii	0.25/1	8/>32	0.5/4	2/32	8/>32	>16/>32	>2/>2	0.5/2	>64/>128
	0.016–8	≤0.25–>32	≤0.016–8	0.13–>32	≤0.25–>32	0.13–>64	0.016–>32	0.13–>4	≤0.5–>128
	188	159	188	188	188	128	188	155	128
Acinetobacter baumannii CARB-I/R,^{^b} FQ-R,^{^d} AG-R	0.5/2	>8/>32	2/8	>8/>32	>8/>32	>32/>32	>4/16	0.5/1	>64/>128
	≤0.016–4	2–>32	0.13–8	>8–>32	>8–>32	>16–>32	>2–>32	0.13–>4	64–>128
	52	43	52	52	52	37	52	43	44
Acinetobacter baumannii TET-R	0.5/2	>8/>32	2/4	>8/>32	>8/>32	>32/>32	>4/32	0.5/1	>64/>128
	0.06–2	>8–>32	0.25–8	≤0.25–>32	≤0.25–>32	4–>64	≤0.25–>32	0.13–>4	4–>128
	69	69	69	69	69	39	69	68	56
Acinetobacter lwoffii	0.13/0.25	1/2	0.13/0.5	≤1/4	≤0.25/1	1/16	≤0.25/≤0.25	0.25/>2	≤0.5/8
	0.03–0.25	≤0.25–>8	0.06–0.5	≤0.25–>8	≤0.25–>8	≤0.5–>64	≤0.25–2	≤0.13–4	≤0.5–16
	34	34	34	34	34	34	34	34	34
Burkholderia cenocepacia	8/32	>32/>32	8/32	32/>32	>32/>32	16/32	4/8	>32/>32	16/>128
	0.13–32	16–>32	0.25–>32	1–>32	>32–>32	2–>32	0.5–>32	>32–>32	0.5–>128
	10	10	10	10	10	10	10	10	10
Citrobacter freundii	0.25/1	1/>8	0.5/2	0.5/2	0.5/>8	1/32	<0.25/>2	0.5/1	4/>128
	0.06–2	0.5–>8	0.13–8	0.004–>32	≤0.25–>32	0.06–>64	0.008–>4	0.25–>2	0.25–>128
	115	65	115	103	115	115	115	64	115
Citrobacter freundii 3rd-GC-I/R^{^c}	0.5/1	2/8	1/2	1/16	0.5/>32	>16/>64	1/>4	0.25/1	>64/>128
	0.13–2	1–>8	0.25–8	0.25–>32	≤0.25–>32	4–>64	0.016–>4	0.25–>2	2–>128
	42	16	42	39	42	42	42	16	42
Enterobacter cloacae	0.5/2	2/>8	0.5/2	0.5/2	0.5/8	2/>64	≤0.25/>4	0.5/>4	4/>64
	0.03–4	0.5–>32	0.06–8	0.03–>32	≤0.25–>32	0.03–>64	0.008–>32	≤0.13–>32	0.5–>128
	270	218	270	270	270	246	270	178	220
Enterobacter cloacae 3rd-GC-I/R	0.5/2	4/>8	1/4	0.5/4	0.5/16	>32/>64	0.25/>4	0.25/>2	>64/>128
	0.03–4	1–>32	0.06–8	0.03–>32	≤0.25–>32	2–>64	0.008–>32	≤0.13–>32	2–>128
	122	93	122	122	122	122	122	81	107
Enterobacter cloacae CARB-I/R	0.5/2	4/>32	0.5/4	2/16	1/>32	>32/>64	≤0.25/>4	0.25/>4	>64/>128
	0.25–4	2–>32	0.13–4	≤0.016–>32	≤0.25–>32	0.13–>64	0.03–>32	≤0.13–>32	1–>128
	34	31	34	34	34	26	34	21	21
Enterobacter cloacae FQ-R	2/4	8/>32	2/4	0.5/8	1/>32	>32/>64	>4/32	0.25/1	>64/>128
	0.25–4	2–>32	0.25–8	≤0.016–>32	≤0.25–>32	0.5–>64	>2–>32	≤0.13–>4	2–>128
	36	29	36	36	36	35	36	21	27
Enterobacter cloacae AG-R	0.5/2	8/>32	1/4	0.5/16	16/>32	>32/>64	>2/>4	0.25/1	>64/>128
	0.25–4	1–>32	0.25–8	0.13–>32	>8–>32	0.25–>64	≤0.016–>32	≤0.13–1	2–>128
	26	20	26	26	26	26	26	15	22
Enterobacter cloacae TET-R	2/4	>8/>32	1/4	0.25/2	1/>32	32/>64	4/16	0.25/>4	16/>64
	0.25–4	>8–>32	0.25–8	0.03–>32	≤0.25–>32	0.13–>64	0.03–>32	≤0.13–>32	2–>128
	25	25	25	25	25	25	25	21	16
Enterobacter aerogenes	0.25/1	2/8	0.5/2	≤1/1	≤0.25/0.5	≤0.5/>32	≤0.25/≤0.25	0.25/0.5	4/>64
	0.13–2	0.5–>8	0.25–4	≤0.25–8	≤0.25–8	≤0.5–>64	≤0.25–>4	≤0.13–>4	≤0.5–>64
	77	77	77	77	77	77	77	77	77
Enterobacter aerogenes 3rd-GC-I/R	0.25/1	2/8	0.5/2	0.5/1	≤0.25/1	32/>32	≤0.25/>4	0.25/1	64/>64
	0.13–2	1–>8	0.25–4	≤0.25–8	≤0.25–2	4–>64	≤0.25–>4	≤0.13–1	8–>64
	27	27	27	27	27	27	27	27	27
Escherichia coli	0.25/0.5	4/>32	0.25/0.5	0.25/0.5	1/>8	≤0.5/>32	≤0.25/>4	0.5/0.5	2/>64
	≤0.016–4	0.25–>64	0.06–>8	≤0.002–>32	≤0.25–>32	≤0.016–>64	≤0.25–>32	≤0.13–4	≤0.5–>128
	445	390	445	445	445	445	445	216	359
Escherichia coli 3rd-GC-I/R	0.25/0.5	>8/>32	0.25/1	0.06/0.5	2/>32	>32/>64	>4/32	0.25/0.5	8/128
	≤0.016–1	0.5–>32	0.03–>8	≤1–>32	≤0.25–>32	2–>64	≤0.25–>32	≤0.13–4	≤0.5–>128
	127	113	127	127	127	127	127	69	93
Escherichia coli FQ-R	0.25/0.5	>8/>32	0.25/0.5	0.13/≤0.5	4/>32	>16/>64	>4/32	0.25/0.5	8/>64
	≤0.016–4	0.25–>32	0.06–>8	≤1–>32	0.25–>32	0.06–>64	>2–>32	≤0.13–4	1–>128
	143	118	143	143	143	143	143	72	142
Escherichia coli AG-R	0.25/0.5	>8/>32	0.25/0.5	0.063/≤0.5	>8/>32	32/>64	>4/32	0.25/0.5	8/>64
	≤0.016–1	0.25–>32	0.063–>8	≤1–>32	>8–>32	0.06–>64	≤0.25–>32	≤0.13–0.5	≤0.5–>128
	79	69	79	79	79	79	79	44	78
Escherichia coli AG-R, FQ-R, 3rd-GC-I/R	0.25/0.5	>8/>32	0.25/0.5	0.063/0.5	>32/>32	>32/>64	>4/32	0.25/0.5	8/>128
	≤0.016–1	0.5–>32	0.063–>8	≤1–>32	>8–>32	4–>64	>2–>32	≤0.12–0.5	1–>128
	40	35	40	40	40	40	40	21	40
Escherichia coli TET-R	0.25/0.5	16/>32	0.25/0.5	0.063/≤0.5	2/>8	4/>32	1/32	0.25/0.5	4/>64
	≤0.016–2	>8–>64	0.06–4	≤1–>32	≤0.25–>32	0.06–>64	≤0.25–>32	≤0.13–4	≤0.5–>128
	157	157	157	157	157	157	157	94	148
Haemophilus influenzae	0.13/0.25	0.5/1	0.13/0.25	1/2	ND	<0.03/0.13	0.016/0.03	ND	ND
	≤0.016–0.5	≤0.06–16	≤0.016–1	0.06–8	ND	≤0.016–0.5	0.004–0.13	ND	ND
	114	114	114	101	ND	114	114	ND	ND
Klebsiella pneumoniae	0.5/2	4/>32	0.5/2	0.25/>8	0.5/>8	8/>32	0.5/>32	0.5/1	8/>128
	0.03–16	≤0.25–>64	0.13–16	≤0.002–>32	≤0.25–>32	≤0.016–>64	≤0.25–>64	≤0.13–>16	≤0.5–>128
	394	339	394	394	223	394	394	209	394
Klebsiella pneumoniae 3rd-GC-I/R	0.5/2	8/>32	1/4	1/16	4/16	>32/64	>4/>32	0.5/4	>64/>128
	0.03–16	1–>64	0.13–16	≤1–>32	0.25–>32	4–>64	≤0.25–>64	≤0.13–>16	0.5–>128
	210	187	210	210	82	210	210	110	209
Klebsiella pneumoniae CARB-I/R	0.5/2	8/>32	1/2	>8/>32	4/>8	>32/>32	>4/>32	0.5/>4	>64/>128
	0.13–16	1–>32	0.25–16	2–>32	0.25–>32	1–>64	0.06–>64	0.13–>16	4–>128
	90	81	90	90	50	90	90	57	90
Klebsiella pneumoniae FQ-R	0.5/2	8/>32	1/2	1/32	4/32	>32/>32	>4/>32	0.5/>4	>64/>128
	0.13–16	1–>32	0.13–16	≤1–>32	≤0.25–>32	0.25–>64	>2–>64	0.13–>16	4–>128
	156	134	156	156	82	156	156	78	156
Klebsiella pneumoniae AG-R	0.5/2	8/>32	1/4	0.5/32	>8/>32	>32/>64	>4/>32	0.5/1	>64/>128
	0.06–16	1–>32	0.13–16	≤1–>32	>8–>32	0.25–>64	≤0.25–>64	≤0.13–>16	2–>128
	119	106	119	119	59	119	119	61	118
Klebsiella pneumoniae AG-R, FQ-R, 3rd-GC-I/R	0.5/2	8/>32	1/4	1/32	>8/>32	>32/>32	8/>32	0.5/1	>64/>128
	0.13–16	2–>32	0.13–16	≤1–>32	>8–>32	8–>64	>2–>64	0.13- >16	4–>128
	74	66	74	74	35	74	74	36	74
Klebsiella pneumoniae AG-R, FQ-R, CARB-I/R	0.5/2	8/>32	1/2	>8/>32	>8/>32	>32/>32	>4/>32	0.5/>4	>128/>128
	0.13–16	4–>32	0.25–16	2–>32	>8–>32	>16–>64	>2–>64	0.13–>16	>64–>128
	37	33	37	37	21	37	37	21	37
Klebsiella oxytoca	0.5/1	1/>32	0.5/2	≤1/≤1	0.5/>32	≤0.5/>32	≤0.25/4	≤0.13/0.13	2/16
	0.03–2	0.5–>32	0.06–4	0.004–1	≤0.13–>32	≤0.016–>32	0.03–>32	0.03–>2	≤0.5–>64
	48	48	48	48	48	48	48	41	48
Klebsiella oxytoca 3rd-GC-I/R	0.5/1	>32/>32	0.25/0.5	0.06/0.25	>32/>32	>32/>32	0.5/>32	0.13/0.13	8/>32
	0.03–1	0.5–>32	0.06–1	0.03–1	0.5–>32	4–>32	0.03–>32	0.03–0.13	0.5–>32
	11	11	11	11	11	11	11	11	11
Legionella pneumophila	1/2	4/8	ND	ND	ND	ND	ND	ND	ND
	0.016–2	0.5–8	ND	ND	ND	ND	ND	ND	ND
	70	70	ND	ND	ND	ND	ND	ND	ND
Moraxella catarrhalis	0.03/0.06	≤0.25/0.5	0.06/0.13	≤0.25/≤0.25	≤0.25/≤0.25	≤0.5/≤0.5	≤0.25/≤0.25	1/1	≤0.5/≤0.5
	≤0.016–0.06	≤0.06–>32	≤0.016–0.13	≤0.25–≤0.25	≤0.06–0.25	≤0.5–2	≤0.25–≤0.25	0.5–2	≤0.5–2
	92	92	92	78	78	78	92	28	28
Morganella morganii	1/2	2/>8	2/4	≤1/2	1/>8	≤0.5/8	≤0.25/4	>2/>4	≤0.5/2
	0.5–4	0.5–>8	0.25–8	0.008–4	≤0.25–>8	≤0.016–>16	0.03–>4	>2–>4	≤0.5–>64
	43	43	43	43	43	43	43	39	43
Proteus mirabilis	1/2	>8/32	4/8	2/4	1/>8	≤0.5/1	≤0.25/>4	>2/>4	≤0.5/2
	0.25–16	2–>64	0.5–16	0.008–>32	≤0.25–>64	≤0.016–>64	0.016–>64	>2–>4	≤0.016–64
	166	111	166	166	166	166	166	95	157
Proteus mirabilis 3rd-GC-I/R	1/4	>8/64	4/8	4/8	8/16	8/>32	>2/8	ND	2/4
	0.5–8	>8–64	1–16	0.25–32	0.5–>64	4–>64	≤0.25–16	>2–>4	≤0.5–64
	21	15	21	21	21	21	21	9	19
Proteus mirabilis CARB-R	1/4	>8/32	4/8	2/8	1/>8	≤0.5/2	≤0.25/>4	>2/>4	≤0.5/2
	0.25–16	2–>64	1–16	0.06–>32	≤0.25–>64	≤0.016–>64	0.016–>64	>2–>4	≤0.06–>64
	136	81	136	136	136	136	136	67	127
Proteus mirabilis FQ-R	2/4	>8/64	4/8	4/8	2/16	≤0.5/16	>4/16	>2/>4	1/2
	0.5–16	>8–>64	1–16	0.25–32	≤0.25–>64	≤0.016–>64	>2–>64	>2–>4	≤0.13–64
	43	26	43	43	43	43	43	19	38
Proteus mirabilis AG-R	2/4	>8/>32	4/8	2/8	>8/>64	≤0.5/32	>2/>4	>2/>4	0.5/4
	0.5–8	>8–64	2–8	0.25–32	>8–>64	≤0.016–>64	0.016–32	>2–>4	≤0.13–8
	24	16	24	24	24	24	24	12	23
Proteus mirabilis TET-R	1/2	>8/32	4/8	2/8	1/>8	≤0.5/1	≤0.25/>4	>2/>4	≤0.5/2
	0.25–16	>8–>64	0.5–16	0.008–>32	≤0.25–>64	≤0.015–>64	0.03–>64	>2–>4	≤0.5–>64
	109	109	109	109	109	109	109	93	100
Proteus vulgaris	0.5/1	8/>8	2/4	≤1/2	1/4	≤0.5/32	≤0.25/0.5	>2/>2	≤0.5/1
	0.25–2	1–>8	0.5–8	≤0.5–4	≤0.25–>8	≤0.03–>64	≤0.25–4	>2–>4	≤0.5–4
	55	55	55	55	55	55	55	55	55
Providencia stuartii	1/2	>8/>8	2/4	2/4	4/32	<0.5/16	>2/>4	>2/>2	4/64
	0.13–8	<0.25–>8	0.06–16	0.25–16	≤0.25–>32	≤0.016–>64	0.016–>4	>2–>4	≤0.13–>128
	101	51	101	101	101	101	101	51	101
Pseudomonas aeruginosa	8/32	>8/64	16/32	2/>8	2/>8	>16/>32	1/>4	1/2	8/>128
	1–>32	8–64	1–>32	0.13–>32	0.13–>32	1–>64	0.06–>32	0.25–4	>64–>128
	145	93	145	145	145	145	145	85	145
Salmonella spp.	0.25/0.25	1/>8	0.25/0.5	≤1/≤1	0.5/1	≤0.5/≤0.5	≤0.25/≤0.25	≤0.13/0.5	2/4
	0.13–0.5	0.5–>8	0.13–1	≤1–8	≤0.25–>8	≤0.5–≤0.5	≤0.25–>4	≤0.13–2	1–64
	30	30	30	30	30	30	30	30	30
Serratia marcescens	1/1	>8/>8	1/2	0.5/1	0.5/1	≤0.5/1	≤0.25/1	>2/>4	2/4
	0.25–8	2–>8	0.5–4	≤0.25–2	≤0.25–8	≤0.5–>64	≤0.25–>4	0.25–>4	≤0.5–>64
	112	112	112	112	112	112	112	112	112
Shigella spp.	0.13/0.5	>8/>8	0.25/0.5	≤1/≤1	1/1	≤0.5/≤0.5	≤0.25/0.5	≤0.13/≤0.13	2/2
	0.06–1	≤0.25–>8	0.13–1	≤1–≤1	≤0.25–>8	≤0.5–2	≤0.25–1	≤0.13–≤0.13	≤0.5–4
	30	30	30	30	30	30	30	30	30
Stenotrophomonas maltophilia	0.5/2	>8/32	0.5/4	>8/>32	>8/>32	>32/>32	1/>4	>2/>32	>64/>128
	≤0.016–8	0.5–>32	0.03–8	2–>32	≤0.25–>32	1–>64	0.13–32	≤0.13–>32	8–>128
	105	105	105	105	105	105	105	104	105

↵a CARB, carbapenem (imipenem, meropenem, or ertapenem); AG, aminoglycoside (gentamicin or tobramycin); 3rd-GC, third-generation cephalosporin (ceftazidime, cefotaxime, or ceftriaxone); FQ, fluoroquinolone (levofloxacin or ciprofloxacin); ERV, eravacycline; TET, tetracycline; TGC, tigecycline; CST, colistin; PTZ, piperacillin-tazobactam; ND, not determined.
↵b For Enterobacteriaceae, carbapenem-I/R isolates were defined as having an imipenem/meropenem MIC of ≥2 μg/ml or an ertapenem MIC of ≥1 μg/ml, and for Acinetobacter, carbapenem-I/R isolates were defined as having an imipenem/meropenem MIC of ≥16 μg/ml.
↵c Third-generation cephalosporin-I/R isolates were defined as having a ceftazidime MIC of ≥8 μg/ml and a cefotaxime/ceftriaxone MIC of ≥2 μg/ml.
↵d Fluoroquinolone-resistant (FQ-R) isolates were defined as having a levofloxacin MIC of ≥8 μg/ml or a ciprofloxacin MIC of ≥4 μg/ml.

Table 2

Susceptibilities of Gram-positive aerobic bacteria to eravacycline and comparators^{^a}

Organism	MIC_50/90 (μg/ml), MIC range (μg/ml), and no. of isolates
Organism	ERV	TET	TGC	DAP	LZD	VAN	LEV	MACRO
Enterococcus faecalis	0.06/0.13	32/>32	0.13/0.25	2/4	2/2	2/>64	>8/>32	>8/>8
	≤0.016–0.13	0.13–>32	≤0.016–0.5	0.13–8	≤0.5–32	0.5–>64	0.25–>32	≤0.13–>8
	194	98	194	194	194	150	194	59
Enterococcus faecalis VSE	0.06/0.13	32/>32	0.13/0.25	2/4	2/2	1/2	2/>32	>4/>8
	≤0.016–0.13	0.13–>32	≤0.016–0.5	0.13–8	≤0.5–32	0.5–4	0.25–>32	≤0.13–>8
	121	70	121	121	121	92	121	38
Enterococcus faecalis VRE	0.06/0.13	32/>32	0.13/0.25	2/4	2/2	>64/>64	>32/>32	>8/>8
	≤0.016–0.13	1–>32	0.03–0.25	0.13–8	1–8	>16–>64	0.25–>32	2–>8
	73	28	73	73	73	58	73	21
Enterococcus faecalis FQ-R	0.06/0.13	32/>32	0.13/0.25	2/4	2/2	>64/>64	>32/>32	>8/>8
	≤0.016–0.13	0.13–>32	≤0.016–0.5	≤0.5–8	1–32	1–>64	>4–>32	≤0.13–32
	111	48	111	111	111	87	111	34
Enterococcus faecium	0.06/0.06	≤2/>32	0.06/0.13	4/8	2/4	2/>64	>32/>32	>8/>8
	≤0.016–0.5	0.25–>32	≤0.016–0.5	1–16	≤0.5–32	≤0.5–>64	0.25–>32	0.25–>8
	153	59	153	153	153	108	153	56
Enterococcus faecium VSE	0.06/0.13	1/>32	0.06/0.13	4/8	2/2	1/1	>8/>32	>8/>8
	0.03–0.5	0.25–>32	0.03–0.25	1–8	1–4	≤0.5–4	0.25–>32	0.25–>8
	84	33	84	84	84	58	84	33
Enterococcus faecium VRE	0.06/0.06	32/>32	0.06/0.13	4/8	2/4	>64/>64	>32/>32	>8/>8
	≤0.016–0.25	0.25–>32	0.03–0.5	1–16	≤0.5–32	>16–>64	1–>32	8–>8
	69	26	69	69	69	49	69	24
Enterococcus faecium FQ-R	0.06/0.06	2/>32	0.06/0.12	4/8	2/4	32/>64	>32/>32	>8/>8
	≤0.016–0.5	0.25–>32	≤0.016–0.5	1–16	≤0.5–32	≤0.5–>64	>4–>32	>4–>8
	127	48	127	127	127	88	127	45
Enterococcus faecium DAP-NS	0.06/0.06	ND	0.06/0.13	8/16	4/4	>64/>64	>32/>32	ND
	≤0.016–0.5	ND	0.03–0.25	8–16	1–32	0.5–>64	2–>32	ND
	44	ND	44	44	44	44	44	ND
Enterococcus spp.	0.03/0.06	0.5/32	0.13/0.13	0.5/2	2/2	ND	1/>8	0.5/>8
	≤0.016–0.13	≤0.06–>32	≤0.016–0.25	0.25–4	1–2	ND	≤0.13–>8	≤0.13–>8
	29	29	29	29	29	ND	29	29
Staphylococcus aureus	0.06/0.25	0.25/32	0.13/0.25	1/1	2/4	1/1	1/32	>8/>32
	≤0.016–4	0.06–>64	≤0.016–16	0.063–4	1–64	0.5–8	0.06–>64	0.13–>64
	408	245	408	407	407	258	399	237
MRSA	0.06/0.13	0.25/32	0.13/0.25	1/1	2/4	1/1	8/>32	>8/>32
	0.016–4	0.063–>64	≤0.016–1	0.063–4	1–64	0.5–8	0.06–>64	0.13–>64
	284	177	284	283	283	202	275	169
MRSA PVL⁺	0.03/0.03	0.25/0.25	0.13/0.13	0.5/1	1/2	1/1	0.25/>2	>4/>4
	≤0.016–0.03	0.13–0.25	0.06–0.13	0.5–1	1–2	1–1	0.25–>2	1–>4
	30	30	30	30	30	30	30	30
Staphylococcus aureus MACRO-R^{^b}	0.06/0.25	0.25/32	0.13/0.25	0.5/1	2/4	1/1	8/32	>8/>32
	≤0.016–4	0.06–>64	≤0.016–16	0.13–4	1–64	0.5–8	0.06–>64	>4–>64
	132	132	132	131	131	70	132	132
Staphylococcus aureus FQ-R	0.06/0.13	0.25/32	0.12/0.25	1/1	2/4	1/1	>8/>32	>8/>32
	≤0.016–2	0.06–>64	≤0.016–16	0.125–2	1–64	0.5–8	>2–>64	0.25–>64
	178	109	178	178	178	126	174	105
Staphylococcus aureus MACRO-R, FQ-R	0.06/0.25	0.25/>32	0.13/0.25	0.5/1	2/4	1/2	>8/32	>8/>32
	≤0.016–2	0.06–>64	≤0.016–16	0.13–2	1–64	0.5–8	>2–>64	>4–>64
	83	83	83	83	83	45	83	83
MSSA	0.13/0.25	0.5/1	0.13/0.25	1/1	4/4	1/1	0.25/1	1/>8
	0.03–0.25	0.25–32	0.06–0.25	0.25–1	2–4	0.5–2	0.13–>32	0.25–>8
	124	68	124	124	124	56	124	68
Coagulase-negative staphylococci	0.06/0.5	0.25/32	0.25/1	1/1	2/2	1/2	0.5/>32	0.5/>8
	≤0.016–2	≤0.06–>32	0.03–2	0.25–2	≤0.5–4	0.5–2	0.13–>32	≤0.13–>8
	165	59	165	165	165	111	165	59
Coagulase-negative staphylococci, methicillin sensitive	0.06/0.5	0.25/32	0.25/1	1/1	2/2	1/2	0.25/>8	0.25/>8
	≤0.016–1	≤0.06–>32	0.03–2	0.25–2	≤0.5–4	0.5–2	0.13–>32	≤0.13–>8
	89	37	89	89	89	54	89	37
Coagulase-negative staphylococci, methicillin resistant	0.06/0.5	0.25/>32	0.13/0.5	1/1	1/2	1/2	8/>32	>4/>8
	0.03–2	0.25–>32	0.06–1	0.25–2	≤0.5–2	0.5–2	0.13–>32	0.25–>8
	76	22	76	76	76	57	76	22
Streptococcus pneumoniae	0.016/0.016	0.25/>8	0.016/0.03	≤0.03/0.5	0.5/1	0.25/0.5	1/1	2/>2
	≤0.008–0.03	≤0.03–>8	≤0.008–0.06	≤0.03–2	≤0.13–2	0.13–0.5	≤0.03–>8	≤0.03–>2
	182	100	182	182	182	82	182	100
Streptococcus pneumoniae penicillin resistant^{^c}	0.016/0.016	>8/>8	0.016/0.03	≤0.03/0.5	0.5/1	0.25/0.25	1/1	>2/>2
	≤0.008–0.03	0.13–>8	≤0.008–0.03	≤0.03–0.5	0.25–1	0.13–0.5	0.5–>8	≤0.03–>2
	60	33	60	60	60	27	60	33
Streptococcus pneumoniae MACRO-R^{^d}	≤0.008/0.016	>8/>8	0.016/0.03	≤0.03/≤0.03	0.5/0.5	ND	1/1	>2/>2
	≤0.008–0.016	≤0.03–>8	≤0.008–0.03	≤0.03–0.13	0.25–1	ND	0.5–>8	2–>2
	53	53	53	53	53	ND	53	53
Streptococcus pneumoniae penicillin resistant, MACRO-R	≤0.008/0.016	>8/<8	0.016/0.03	≤0.03/≤0.03	0.5/0.5	ND	1/1	>2/>2
	≤0.008–0.016	0.13–>8	≤0.008–0.03	≤0.03–≤0.03	0.25–0.5	ND	0.5–>8	2–>2
	29	29	29	29	29	ND	29	29
Streptococcus pneumoniae TET-R	≤0.008/0.016	>8/>8	0.016/0.03	≤0.03/≤0.03	0.5/0.5	ND	1/1	>2/>2
	≤0.008–0.016	>8–>8	≤0.008–0.03	≤0.03–0.06	0.25–0.5	ND	0.5–>2	2–>2
	34	34	34	34	34	ND	34	34
Streptococcus pyogenes	0.03/0.03	0.25/0.25	0.03/0.06	0.13/0.13	1/2	ND	0.5/1	0.06/0.06
	0.015–0.13	0.13–>8	≤0.016–0.13	≤0.03–0.25	0.5–2	ND	0.25–2	≤0.03–0.13
	74	20	74	74	74	ND	74	20
Streptococcus agalactiae	0.03/0.06	>8/>8	0.03/0.06	0.06/0.5	1/2	0.5/0.5	0.5/1	0.06/>4
	0.016–0.06	0.25–>8	0.016–0.13	≤0.03–1	0.5–2	0.25–0.5	0.5–2	≤0.03–>4
	123	79	123	123	123	48	123	79
Streptococcus anginosus	0.016/0.031	0.5/>16	0.016/0.06	0.25/0.5	1/2	0.5/1	0.5/1	0.03/>0.5
	≤0.008–0.13	≤0.06–>16	≤0.008–0.25	≤0.03–0.5	≤0.25–2	≤0.008–1	≤0.25–2	≤0.016–>2
	47	47	47	25	47	46	25	25
Streptococcus intermedius	0.016/0.06	0.25/>4	0.03/0.13	0.5/1	1/1	0.5/0.5	1/2	0.06/>0.5
	≤0.008–0.06	≤0.06–>4	≤0.008–0.25	≤0.03–>1	≤0.25–1	≤0.06–0.5	≤0.25–>4	≤0.016–>0.5
	31	31	31	31	31	31	30	31
Streptococcus mitis	0.016/0.06	0.5/>4	0.03/0.13	0.5/1	1/1	0.5/0.5	1/2	>0.5/>0.5
	≤0.008–0.06	0.13–>8	≤0.008–0.25	0.06–>1	0.5–1	≤0.06–1	0.5–>4	≤0.016–>2
	32	32	32	32	32	31	32	32
Streptococcus spp.	0.016/0.13	1/>8	0.03/0.13	0.13/1	0.5/1	0.5/1	1/2	0.06/>2
	≤0.008–0.25	≤0.06–>8	≤0.008–0.25	≤0.03–1	≤0.25–2	≤0.06–1	≤0.25–2	≤0.016–>2
	62	62	62	62	62	21	62	62

↵a MACRO, macrolide (erythromycin, azithromycin, or clarithromycin); ND, not determined; ERV, eravacycline; TET, tetracycline; TGC, tigecycline; DAP, daptomycin; LZD, linezolid; VAN, vancomycin; LEV, levofloxacin; DAP-NS, daptomycin nonsusceptible; PVL⁺, Panton-Valentine leukocidin positive.
↵b Macrolide-resistant staphylococci were defined as having an erythromycin/azithromycin/clarithromycin MIC of ≥8 μg/ml.
↵c Penicillin-resistant streptococcal isolates were defined as having an MIC of ≥2 μg/ml for the oral penicillin breakpoint.
↵d Macrolide-resistant streptococcal isolates were defined as having an erythromycin/clarithromycin MIC of ≥1 μg/ml and an azithromycin MIC of ≥2 μg/ml.

Table 3

Susceptibilities of anaerobic bacteria to eravacycline and comparators^{^a}

Organism	MIC_50/90 (μg/ml), MIC range (μg/ml), and no. of isolates
Organism	ERV	TGC	CARB	MTZ	VAN
Actinomyces spp.	ND	ND	ND	ND	ND
	0.25–0.25	0.25–0.5	ND	4–>16	ND
	5	5	ND	5	ND
Anaerococcus spp.	0.13/0.13	0.13/0.25	ND	2/2	ND
	0.03–0.25	0.06–0.25	ND	0.5–4	ND
	10	10	ND	10	ND
Bacteroides fragilis	0.5/1	0.5/4	0.25/1	1/1	>16/>16
	0.06–2	0.13–8	0.13–4	0.25–>16	16–>16
	36	36	16	31	11
B. fragilis cefinase positive	0.5/1	1/4	ND	1/1	ND
	0.13–2	0.25–8	ND	0.25–1	ND
	20	20	ND	20	ND
Bacteroides ovatus	1/4	0.5/16	0.25/0.25	1/2	>16/>16
	0.016–8	0.06–32	0.03–1	0.13–>16	8–>16
	11	11	11	10	10
Bacteroides thetaiotaomicron	1/4	8/16	0.5/2	1/2	>16/>16
	0.13–4	0.25–16	0.13–4	0.5–>16	16–>16
	11	11	11	10	10
Bacteroides vulgatus	0.25/0.25	0.5/0.5	0.25/1	0.5/1	>16/>16
	0.13–1	0.13–4	0.25–1	0.5–1	16–>16
	12	12	12	10	10
Bifidobacterium spp.	ND	ND	ND	ND	ND
	0.13–0.5	0.25–0.5	ND	2–>16	ND
	7	7	ND	6	ND
Clostridium difficile	0.06/0.13	0.13/0.13	4/8	1/1	1/2
	0.03–0.25	0.06–0.5	0.25–8	0.5–2	0.5–4
	11	11	11	11	11
Clostridium perfringens	1/2	1/4	0.13/0.5	4/16	1/>16
	0.06–4	0.13–8	0.06–1	2–>16	0.5–>16
	11	11	11	10	10
Eggerthella lenta	0.25/0.25	0.5/0.5	ND	0.5/0.5	ND
	0.25–0.25	0.25–0.5	ND	0.25–0.5	ND
	12	12	ND	12	ND
Finegoldia magna	0.25/0.5	0.25/0.25	ND	0.5/1	ND
	0.13–0.5	0.13–0.25	ND	≤0.13–1	ND
	10	10	ND	10	ND
Fusobacterium spp.	0.13/0.25	0.13/0.5	ND	≤0.13/0.25	ND
	0.03–0.25	0.06–0.5	ND	≤0.13–0.25	ND
	21	21	ND	21	ND
Lactobacillus spp.	0.25/0.5	0.5/0.5	ND	>16/>16	ND
	0.25–1	0.25–1	ND	>16–>16	ND
	7	7	ND	7	ND
Parabacteroides distasonis	0.5/1	1/2	ND	1/1	ND
	0.25–1	0.25–4	ND	0.5–1	ND
	10	10	ND	10	ND
Peptoniphilus asaccharolyticus	0.06/0.13	0.13/0.25	ND	1/2	ND
	0.03–0.13	0.06–0.25	ND	0.5–2	ND
	10	10	ND	10	ND
Peptostreptococcus anaerobius	0.06/0.25	0.06/0.25	0.06/1	1/2	0.5/2
	0.016–0.25	0.016–0.5	0.03–1	0.25–2	0.5–>16
	10	10	10	10	10
Peptostreptococcus micros	0.016/0.25	0.03/0.25	0.016/0.03	0.25/>16	1/1
	0.016–0.5	0.016–1	≤0.008–0.03	≤0.008–>16	0.5–2
	10	10	10	10	10
Porphyromonas asaccharolytica	0.03/0.06	0.06/0.06	0.016/0.03	1/2	0.25/0.5
	0.016–0.13	0.03–0.13	≤0.008–0.06	0.5–4	0.13–1
	10	10	10	10	10
Prevotella bivia	1/1	1/2	ND	1/4	ND
	0.13–1	0.03–2	ND	0.5–4	ND
	13	13	ND	13	ND
Prevotella buccae	0.06/0.13	0.13/0.13	ND	0.5/1	ND
	0.03–0.13	0.06–0.25	ND	0.25–1	ND
	10	10	ND	10	ND
Prevotella disiens	0.13/0.25	0.25/0.5	ND	1/1	ND
	0.06–0.25	0.13–0.5	ND	0.5–2	ND
	12	12	ND	12	ND
Prevotella intermedia	0.06/0.13	0.25/0.25	ND	0.5/0.5	ND
	0.03–0.13	0.13–0.25	ND	0.25–1	ND
	10	10	ND	10	ND
Prevotella melaninogenica	0.13/1	0.5/1	ND	0.25/1	ND
	0.06–1	0.06–4	ND	≤0.008–>16	1–>16
	13	13	ND	13	8
Prevotella spp.	ND	ND	ND	ND	ND
	0.03–1	0.06–0.5	ND	0.25–>16	ND
	7	7	ND	7	ND
Propionibacterium acnes	ND	ND	ND	ND	ND
	0.13–0.13	0.13–0.13	ND	>16–>16	ND
	5	5	ND	5	ND

↵a ERV, eravacycline; TGC, tigecycline; MTZ, metronidazole; VAN, vancomycin; CARB, ertapenem or imipenem; ND, not determined.

Table 4

Distribution of tigecycline/eravacycline MIC ratios^{^a} for individual isolates

TGC/ERV MIC ratio	No. of isolates with TGC/ERV ratio
TGC/ERV MIC ratio	A. baumannii	E. coli	E. cloacae	K. pneumoniae	P. mirabilis	B. fragilis
32		2
16	1	4		3
8	39	7	4	4	5	1
4	80	27	21	35	82	6
2	44	106	134	140	65	21
1	20	211	95	185	13	8
0.5	4	86	15	27	0
0.25		2	1		1
Total	188	445	270	394	166	36

↵a For each isolate within a given organism panel, the ratio of the tigecycline MIC to the eravacycline MIC (TGC/ERV MIC) was calculated.

Table 5
Activity of eravacycline against S. aureus strains expressing NorA or MepA efflux pumps
Compound MIC (μg/ml)
SA981 (parent) SA982 (norA) SA983 (parent) SA984 (mepA)
Eravacycline 0.004 0.004 0.004 0.016
Tigecycline 0.063 0.13 0.016 1
Tetracycline 0.5 0.5 0.5 0.5
Ciprofloxacin 0.5 16 2 4
Meropenem 0.25 0.13 0.13 0.13

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Compound	MIC (μg/ml)
Compound	SA981 (parent)	SA982 (norA)	SA983 (parent)	SA984 (mepA)
Eravacycline	0.004	0.004	0.004	0.016
Tigecycline	0.063	0.13	0.016	1
Tetracycline	0.5	0.5	0.5	0.5
Ciprofloxacin	0.5	16	2	4
Meropenem	0.25	0.13	0.13	0.13