TABLE 3.

Activity of KBP-7072 and tetracycline class comparators against Gram-negative clinical isolates

Antimicrobial agent (no. of isolates)	MIC50 (mg/liter)	MIC90 (mg/liter)	MIC range (mg/liter)	CLSIa
				%S	%I	%R
Enterobacterales (410)
KBP-7072	0.25	2	0.06–16
Doxycycline	2	32	0.5 to >32	67.6	5.6	26.8
Minocycline	2	16	0.25 to >32	79.0	6.1	14.9
Omadacycline	2	16	0.5 to >32
Tetracycline	2	>64	0.5 to >64	64.4	3.2	32.4
Tigecycline	0.5	2	0.12–8	93.4b	5.6	1.0
Enterobacterales (133)c tetracycline resistant
KBP-7072	1	4	0.12–16
Doxycycline	32	>32	4 to >32	3.0	15.0	82.0
Minocycline	8	>32	1 to >32	38.3	15.8	45.9
Omadacycline	4	32	0.5 to >32
Tetracycline	>64	>64	16 to >64	0.0	0.0	100
Tigecycline	1	4	0.12–8	79.7	17.3	3.0
Citrobacter freundii species complex (22)
KBP-7072	0.25	0.5	0.12–1
Doxycycline	2	8	1–32	86.4	4.5	9.1
Minocycline	1	8	0.5–16	86.4	9.1	4.5
Omadacycline	1	4	1–8
Tetracycline	1	8	0.5 to >64	86.4	4.5	9.1
Tigecycline	0.25	1	0.12–2	100.0b	0.0	0.0
C. koseri (21)
KBP-7072	0.12	0.25	0.12–0.5
Doxycycline	1	2	0.5–4	100.0	0.0	0.0
Minocycline	0.5	2	0.5–4	100.0	0.0	0.0
Omadacycline	1	1	0.5–2
Tetracycline	1	2	1–4	100.0	0.0	0.0
Tigecycline	0.25	0.25	0.12–0.5	100.0b	0.0	0.0
Enterobacter cloacae species complex (50)
KBP-7072	0.25	0.5	0.25–4
Doxycycline	2	2	1–16	92.0	0.0	8.0
Minocycline	2	4	0.5–32	96.0	0.0	4.0
Omadacycline	2	4	1–16	94.0b,d	2.0	4.0
Tetracycline	2	4	1 to >64	90.0	0.0	10.0
Tigecycline	0.5	0.5	0.25–4	96.0b	4.0	0.0
E. cloacae species complex (18) ceftazidime-nonsusceptible (MIC, ≥8 mg/liter)
KBP-7072	0.25	0.5	0.25–4
Doxycycline	2	4	1–16	94.4	0.0	5.6
Minocycline	2	4	0.5–32	94.4	0.0	5.6
Omadacycline	2	4	1–16	94.4b,d	0.0	5.6
Tetracycline	2	16	1 to >64	88.9	0.0	11.1
Tigecycline	0.5	0.5	0.25–4	94.4b	5.6	0.0
Escherichia coli (77)
KBP-7072	0.12	0.5	0.06–2
Doxycycline	2	32	0.5 to >32	58.4	14.3	27.3
Minocycline	1	8	0.5–32	84.4	7.8	7.8
Omadacycline	1	2	0.5–16
Tetracycline	2	>64	0.5 to >64	57.1	0.0	42.9
Tigecycline	0.25	0.5	0.12–4	98.7b	1.3	0.0
E. coli (26) ESBL phenotype
KBP-7072	0.25	1	0.12–2
Doxycycline	8	32	1–32	38.5	26.9	34.6
Minocycline	2	8	0.5–32	84.6	7.7	7.7
Omadacycline	2	4	0.5–16
Tetracycline	>64	>64	1 to >64	38.5	0.0	61.5
Tigecycline	0.25	1	0.12–4	96.2b	3.8	0.0
Klebsiella aerogenes (21)
KBP-7072	0.25	0.5	0.25–4
Doxycycline	2	4	0.5 to >32	90.5	0.0	9.5
Minocycline	2	2	1 to >32	95.2	0.0	4.8
Omadacycline	2	2	1–32
Tetracycline	2	8	1 to >64	85.7	4.8	9.5
Tigecycline	0.5	0.5	0.25–8	95.2b	0.0	4.8
K. oxytoca (53)
KBP-7072	0.25	0.5	0.12–2
Doxycycline	1	8	0.5–32	88.7	3.8	7.5
Minocycline	1	4	0.25–16	94.3	1.9	3.8
Omadacycline	1	2	0.5–16
Tetracycline	1	8	0.5 to >64	88.7	1.9	9.4
Tigecycline	0.25	1	0.12–2	100.0b	0.0	0.0
K. pneumoniae (80)
KBP-7072	0.25	1	0.12–4
Doxycycline	1	16	0.5 to >32	71.2	3.8	25.0
Minocycline	2	8	0.5 to >32	83.8	7.5	8.8
Omadacycline	2	8	0.5–32	87.5b,d,e	7.5	5.0
Tetracycline	2	>64	0.5 to >64	72.5	0.0	27.5
Tigecycline	0.5	1	0.25–4	96.2b	3.8	0.0
K. pneumoniae (27) ESBL phenotype
KBP-7072	0.5	2	0.25–4
Doxycycline	8	32	1 to >32	40.7	11.1	48.1
Minocycline	4	>32	1 to >32	74.1	7.4	18.5
Omadacycline	4	16	1–32	81.5b,d,e	7.4	11.1
Tetracycline	>64	>64	1 to >64	40.7	0.0	59.3
Tigecycline	0.5	2	0.25–4	92.6b	7.4	0.0
Morganella morganii (20)
KBP-7072	1	2	0.5–8
Doxycycline	32	>32	1 to >32	45.0	0.0	55.0
Minocycline	4	32	1 to >32	50.0	5.0	45.0
Omadacycline	8	8	2 to >32
Tetracycline	32	>64	1 to >64	45.0	0.0	55.0
Tigecycline	1	2	0.5–4	95.0b	5.0	0.0
Proteus mirabilis (22)
KBP-7072	4	8	1–16
Doxycycline	32	>32	16 to >32	0.0	0.0	100.0
Minocycline	16	32	8 to >32	0.0	13.6	86.4
Omadacycline	16	>32	8 to >32
Tetracycline	32	64	32–64	0.0	0.0	100.0
Tigecycline	4	4	1–8	31.8b	59.1	9.1
Providencia spp. (22)f
KBP-7072	4	4	0.5–8
Doxycycline	>32	>32	2 to >32	4.5	4.5	90.9
Minocycline	16	>32	2 to >32	18.2	22.7	59.1
Omadacycline	32	32	4 to >32
Tetracycline	64	>64	2 to >64	9.1	0.0	90.9
Tigecycline	2	4	0.5–4	86.4b	13.6	0.0
Serratia marcescens (22)
KBP-7072	0.5	1	0.5–16
Doxycycline	4	16	2–32	59.1	22.7	18.2
Minocycline	2	4	2–32	90.9	4.5	4.5
Omadacycline	4	8	2 to >32
Tetracycline	8	>64	4 to >64	4.5	45.5	50.0
Tigecycline	1	2	0.5–8	95.5b	0.0	4.5
Acinetobacter baumannii-calcoaceticus species complex (22)
KBP-7072	0.5	1	0.03–1
Doxycycline	1	>32	0.06 to >32	63.6	9.1	27.3
Minocycline	0.5	8	0.03–16	72.7	18.2	9.1
Omadacycline	2	8	0.12–8
Tetracycline	16	>64	1 to >64	40.9	4.5	54.5
Tigecycline	2	4	0.12–4
A. baumannii-calcoaceticus species complex (13) carbapenem resistant
KBP-7072	0.5	1	0.25–1
Doxycycline	8	>32	0.25 to >32	38.5	15.3	46.2
Minocycline	4	16	0.25–16	53.8	30.8	15.4
Omadacycline	4	8	2–8
Tetracycline	64	>64	4 to >64	7.7	0.0	92.3
Tigecycline	4	4	2–4
Pseudomonas aeruginosa (22)
KBP-7072	8	16	0.5 to >32
Doxycycline	16	32	4 to >32
Minocycline	16	32	4 to >32
Omadacycline	32	>32	2 to >32
Tetracycline	16	32	4 to >64
Tigecycline	8	16	0.5 to >16
Stenotrophomonas maltophilia (22)
KBP-7072	0.5	1	0.25–8
Doxycycline	2	4	1–16
Minocycline	0.5	1	0.25–8	95.5	4.5	0.0
Omadacycline	4	8	2–32
Tetracycline	32	64	16–64
Tigecycline	1	2	0.5–16
Haemophilus influenzae (52)
KBP-7072	0.12	0.25	0.06–0.5
Doxycycline	0.5	0.5	0.12–1
Minocycline	0.25	0.5	0.12–0.5
Omadacycline	0.5	1	0.25–2	100.0b,e	0.0	0.0
Tetracycline	0.5	0.5	0.25–8	98.1	0.0	1.9
Tigecycline	0.25	0.25	0.06–0.5	94.2
H. parainfluenzae (12)
KBP-7072	0.25	0.5	0.06–0.5
Doxycycline	0.5	2	0.25–16
Minocycline	1	2	0.25–4
Omadacycline	1	2	0.25–2	100.0b,e	0.0	0.0
Tetracycline	0.5	1	0.25–32	91.7	0.0	8.3
Tigecycline	0.5	0.5	0.06–1
Moraxella catarrhalis (21)
KBP-7072	0.06	0.06	≤0.015 to 0.06
Doxycycline	0.12	0.12	0.06–0.25
Minocycline	0.06	0.06	0.03–0.06
Omadacycline	0.12	0.25	0.06–0.25
Tetracycline	0.25	0.5	0.12–0.5	100.0	0.0	0.0
Tigecycline	0.06	0.06	0.03–0.06

^aCriteria as published by CLSI (22).

^bFDA breakpoints.

^cOrganisms include Citrobacter freundii species complex (2), E. cloacae species complex (5), E. coli (33), K. aerogenes (2), K. oxytoca (5), K. pneumoniae (22), M. morganii (11), P. mirabilis (22), P. rettgeri (11), P. stuartii (9), and S. marcescens (11).

^dUsing ABSSSI breakpoints.

^eUsing CABP breakpoints.

^fOrganisms include Providencia alcalifaciens (1), P. rettgeri (12), and P. stuartii (9).