Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections

Figures & data

Table 1 Pharmacokinetic parameters of tedizolid phosphate and tedizolid after the administration of tedizolid phosphate to rats^28,31

Tedizolid phosphate IV					Tedizolid phosphate OR
Dose (mg/kg)	5 mg/kg (n = 7)^Citation28	10 mg/kg (n = 7)^Citation28	20 mg/kg (n = 9)^Citation28	10 mg/kg^Citation31	20 mg/kg (n = 10)^Citation28	50 mg/kg (n = 8)^Citation28	100 mg/kg (n = 9)^Citation28	10 mg/kg^Citation31
AUC(mcg * min/mL)	313 ± 75.4	44.7 ± 16.9	86.3 ± 27.9	3.216	44.7 ± 16.9	86.3 ± 27.9	163 ± 40.0	2.988
T½ (min)	13.8 ± 3.64	133 ± 30.8	159 ± 32.1	205.2	133 ± 30.8	159 ± 32.1	162 ± 29.6	229.2
Cmax (mcg/mL)	–	–	–	8.81	0.214 ± 0.0833	0.320 ± 0.102	0.440 ± 0.0995	8.37
Tmax (min)	–	–	–	–	45.0 ± 24.5	80.6 ± 26.5	130 ± 73.5	30
Cl (mL/min/kg)	16.0 ± 3.40	45.0 ± 24.5	80.6 ± 26.5	3.11	–	–	–	–
Vdss (mL/kg)	84.7 ± 14.2	0.214 ± 0.0833	0.320 ± 0.102	0.918	–	–	–	–
F (%)	–	–	–	–	3.44	2.66	2.51	92.8
Tedizolid IV					Tedizolid OR
AUC (mcg * min/mL)	905 ± 105	1.780 ± 334	4.070 ± 1.140		2.890 ± 857	8.580 ± 3.230	17.500 ± 6.710
T½ (min)	106 ± 12.0	112 + 19.2	115 ± 29.8		158 ± 24.5	276 ± 113	366 ± 85.7
Cmax (mcg/mL)	12.5 ± 1.16	20.8 ± 3.41	45.4 ± 8.95		14.0 ± 4.43	22.9 ± 8.13	34.6 ± 10.1
Tmax (min)	12.1 ± 4.88	7.85 ± 4.88	10.6 ± 12.6		25.5 ± 14.2	43.1 ± 24.6	65.0 ± 72.3

Abbreviations: AUC, area under the curve; Cl, total body clearance; C_max, maximum concentration; F, absolute oral bioavailability; IV, intravenous; OR, oral; T_½, half-life; T_max, time to maximum concentration; Vd_ss, volume of distribution at steady state.

Table 2 Pharmacokinetic parameters of tedizolid after the administration of multiple doses of tedizolid phosphate to healthy adults^33,37

Dose of tedizolid phosphate	TR-701 200 mg QD OR^Citation37		TR-701 300 mg QD OR^Citation37		TR-701 400 mg QD OR^Citation37		TR-701 200 mg QD IV^Citation33		Linezolid 600 mg BID^Citation37
Parameter	Day 1	Day 15	Day 1	Day 15	Day 1	Day 15	Day 1	Day 7	Day 1	Day 15
Cmax (mcg/mL)	1.8(1.2)	1.8 (0.4)	2.1 (0.5)	2.5 (0.4)	4.2 (0.8)	4.5 (0.9)	2.34 (0.64)	3.01 (0.66)	12.2 (3.0)	14.6 (4.6)
Cmin (mcg/mL)	0.3 (0.1)	0.4 (0.2)	0.4(0.1)	0.5 (0.2)	0.7 (0.2)	0.8 (0.2)	–	–	1.7(1.4)	4.9 (3.3)
Tmax (hr) (range)	3.0(1.5–4.0)	3.0 (2.0–4.0)	2.0(1.5–4.0)	1.8(1.5–4.0)	4.0(1.0–4.0)	3.0 (2.0–8.0)	1.08(0.92–1.50)	1.17(0.92–1.50)	1.0(04–1.5)	1.5(1.0–4.0)
T½ (hr)	11.1 (1.2)	10.2(2.0)	10.1 (1.4)	9.4(1.2)	8.0(1.2)	8.4(1.0)	9.33 (1.5)	124(1.25)	3.8(1.7)	4.7(1.3)
AUC (meg * hr/mL)	21.6(6.5)	22.5 (6.5)	29.6 (7.5)	30.7(6.1)	54.0 (8.2)	53.2 (7.9)	22.29 (4.24)	29.19(6.22)	78.1 (31.6)	108.9(42.7)
Accumulation ratio	1.04		1.04		0.99		–	–	1.39
Cl/F (L/hr)	10.0(2.8)	9.5 (2.7)	10.6(2.4)	10.1 (1.8)	7.6(1.1)	7.7(1.1)	6.37(1.19)	5.87(141)	8.7(3.1)	6.4 (2.7)
V/F (L)	155(29)	143 (51)	155(37)	136(23)	86(13)	92(18)	77.6(15.9)	80.1 (21.0)	43(11)	43(11)

Abbreviations: AUC, area under the curve; BID, twice daily; Cl/F (L/hr), apparent oral clearance; C_max, maximum concentration; C_min, minimum concentration; IV, intravenous; OR, oral; QD, daily; T_½ half-life; T_max, time to maximum concentration; V/F (L), apparent volume of distribution.

Table 3 Proposed minimum inhibitory concentration (MIC) cut-off point and disc diffusions for tedizolid⁴⁸

Microorganism	Cut-off points (S)
	MIC (mcg/mL)	Disc diffusion using a disc of 20 or 10 mcg
Staphylococcus aureus	≤2	≥18
Coagulase-negative staphylococci	≤2	≥18
Enterococcus spp., Streptococcus pneumoniae, and Streptococcus spp. other than S. pneumoniae	≤2	≥15 mm
Corynebacterium jeikeium	≤2	No range recommended due to the reduced number of strains tested
Listeria monocytogenes	≤2	≥15 mm

Abbreviation: S, sensitive.

Table 4 Activity of tedizolid (TR-700) and other antibiotics against Gram-positive microorganisms

Microorganism	Strains tested (n)	Antibiotic	MIC50 (mcg/mL)	MIC90 (mcg/mL)	Range (mcg/mL)
Corynebacterium jeikeium	12^Citation48	Tedizolid	0.25	0.5	0.25–0.50
		Cefotaxime	32	32	8–32
		Levofloxacin	>16	>16	16 >16
		Linezolid	1	1	0.5–1.0
Enterococcus faecalis S to vancomycin	54^Citation48 + 73^Citation50 + 49^Citation54	TR-700^Citation48,Citation50,Citation54	0.25–0.50	0.5–1.0	0.12–1.0
		Linezolid^Citation48,Citation50,Citation54	2	2	0.5–4.0
		Vancomycin^Citation50,Citation54	1–2	2	0.5–4.0
		Cefotaxime^Citation48	>64	>64	0.25 > 64.0
		Levofloxacin^Citation48,Citation54	1–2	>16–64	0.5–64.0
		Ampicillin^Citation54	1	4	0.25–8.0
		Erythromycin^Citation54	4	>128	0.12 to >128.0
		Tetracycline^Citation54	64	64	0.5–128.0
		Teicoplanin^Citation54	0.25	0.5	≤0.12–0.50
E. faecalis R to vancomycin	45^Citation48 + 49^Citation50 + 12^Citation54	TR-700^Citation48,Citation50,Citation54	0.25–0.5	0.5	0.25–1.0
		Linezolid^Citation48,Citation50,Citation54	1–2	1–2	0.5–4.0
		Vancomycin^Citation50,Citation54	>32 to >128	>32 to >128	4 to >128
		Cefotaxime^Citation48	>64	>64	0.25 to >64.0
		Levofloxacin^Citation48,Citation54	>16–64	>16–64	0.5–128.0
		Ampicillin^Citation54	2	4	1–4
		Erythromycin^Citation54	>128	>128	>128
		Tetracycline^Citation54	32	64	0.5–64.0
		Teicoplanin^Citation54	64	64	32–128
E. faecalis R to linezolid	16^Citation51 + 12^Citation53	TR-700^Citation51,Citation53	2–4	4	0.5–8.0
		Linezolid^Citation51	32	32	8–32
		Vancomycin^Citation51	1	>16	1 to >16
Enterococcus faecium S to vancomycin	52^Citation48 + 53^Citation50 + 30^Citation54	TR-700^Citation48,Citation50,Citation54	0.25–0.5	0.25–1	0.06–2.00
		Linezolid^Citation48,Citation50,Citation54	2	2–4	0.5–4.0
		Vancomycin^Citation50,Citation54	0.5–1.0	0.5–1.0	0.25–4.00
		Cefotaxime^Citation48	>64	>64	0.5 to >64
		Levofloxacin^Citation48,Citation54	4–64	>16–64	0.5–128.0
		Ampicillin^Citation54	>128	>128	1 to >128
		Erythromycin^Citation54	>128	>128	0.25 to >128.00
		Tetracycline^Citation54	0.5	1	0.12–32.00
		Teicoplanin^Citation54	0.5	0.5	0.25–2.00
E. faecium R to vancomycin	52^Citation48 + 51^Citation50 + 29^Citation54	TR-700^Citation48,Citation50,Citation54	0.12–0.5	0.25–0.5	0.06–2.00
		Linezolid^Citation48,Citation50,Citation54	1–2	1–4	0.5 to >8.0
		Vancomycin^Citation50,Citation54	>32–128	>32 to >128	8 to >128
		Cefotaxime^Citation48	>64	>64	>64
		Levofloxacin^Citation48,Citation54	>16–64	>16–128	1–128
		Ampicillin^Citation54	>128	>128	64 to >128
		Erythromycin^Citation54	128	>128	64 to >128
		Tetracycline^Citation54	0.25	128	≤0.06–128.00
		Teicoplanin^Citation54	16	64	2–64
E. faecium R to linezolid	36^Citation51 + 45^Citation53	TR-700^Citation51,Citation53	2	2–4	0.5–8.0
		Linezolid^Citation51	32	64	4 to >128
		Vancomycin^Citation53	>16	>16	0.5 to >16
Listeria monocytogenes	33^Citation48	Tedizolid	0.25	0.25	0.25–0.50
		Cefotaxime	32	32	2–32
		Levofloxacin	1	1	1–2
		Linezolid	2	2	2–2
Staphylococcus aureus S to methicillin	105^Citation48 + 95^Citation50 + 30^Citation54	TR-700^Citation48,Citation50,Citation54	0.25–0.50	0.5	0.25–8.00
		Linezolid^Citation48,Citation50,Citation54	2–4	2–4	1 to >8
		Vancomycin^Citation48,Citation50,Citation54	0.5–1.0	1	0.25–2.00
		Oxacillin^Citation48,Citation50,Citation54	0.25–0.50	0.5	0.06–0.50
		Cefotaxime^Citation48	2	2	0.03–4.00
		Levofloxacin^Citation48,Citation54	0.25–0.50	1–4	0.12 to >16.00
		Erythromycin^Citation48,Citation54	0.5	>128	0.5 to >128.0
		Clindamycin^Citation48,Citation54	0.25	0.25	≤0.06–1.00
		Cotrimoxazole^Citation48,Citation54	0.25	2	≤0.06–32.00
		Gentamycin^Citation48,Citation54	0.5	128	0.06 to >128.00
		Tetracycline^Citation48,Citation54	0.5	32	0.25–64.00
S. aureus S to methicillin**	39^Citation55	Tedizolid	0.25	0.25	0.12–0.50
		Linezolid	1	2	0.5–2.0
S. aureus R to methicillin	129^Citation48 + 103^Citation50 + 30^Citation54	TR-700^Citation48,Citation50,Citation54	0.5	0.5–1.0	0.12–16.0
		Linezolid^Citation48,Citation50,Citation54	2	4	1 to >8
		Vancomycin^Citation50	1	1	0.5–2.0
		Oxacillin^Citation50,Citation54	32 to >128	32 to >128	4 to >128
		Cefotaxime^Citation48	16	>64	2 to >64
		Levofloxacin^Citation48,Citation54	8–16	>16 to >128	0.12 to >128.00
		Erythromycin^Citation48,Citation54	>128	>128	0.5 to >128.0
		Clindamycin^Citation48,Citation54	>128	>128	0.25 to >128.00
		Cotrimoxazole^Citation48,Citation54	0.5	>128	0.25 to >128.00
		Gentamycin^Citation48,Citation54	64	>128	0.25 to >128.00
		Tetracycline^Citation48,Citation54	64	64	0.5–128.0
S. aureus R to methicillin community-acquired	100^Citation50	TR-700	0.5	0.5	0.25–1.00
		Linezolid	2	4	1–4
		Vancomycin	4	4	1–4
		Oxacillin	32	32	4 to >32
S. aureus R to methicillin**	124^Citation55	Tedizolid	0.25	0.25	0.12–0.50
		Linezolid	1	2	0.5–2.0
S. aureus S to linezolid*	449^Citation49	TR-700	0.25	0.5	0.125–0.500
		Linezolid	2	2	≤0.25–4.00
		Daptomycin	0.25	0.5	≤0.125–1.000
		Vancomycin	1	1	≤0.5–4.0
		Teicoplanin	≤0.5	1	≤0.5–4.0
–S. aureus S to linezolid, S to oxacillin*	202^Citation49	TR-700	0.25	0.25	0.125–0.500
		Linezolid	1	2	≤0.25–4.00
		Daptomycin	0.25	0.5	≤0.125–1.000
		Vancomycin	1	1	≤0.5–2.0
		Teicoplanin	≤0.5	1	≤0.5–2.0
–S. aureus S to linezolid, R to oxacillin*	247^Citation49	TR-700	0.25	0.5	0.125–0.500
		Linezolid	2	4	≤0.25–4.00
		Daptomycin	0.5	0.5	≤0.125–1.000
		Vancomycin	1	2	≤0.5–4.0
		Teicoplanin	≤0.5	1	≤0.5–4.0
S. aureus R to linezolid*	7^Citation49	TR-700	0.5	NA	0.5
		Linezolid	16	NA	16
		Daptomycin	0.5	NA	0.5
		Vancomycin	2	NA	1–2
		Teicoplanin	1	NA	≤0.5–2.0
S. aureus R to linezolid	13^Citation48 + 17^Citation51 + 5^Citation52	Tedizolid^Citation48,Citation51,Citation52	0.25–4.00	0.2–8.0, NA^Citation52	0.12–16.00
		Cefotaxime^Citation48	>64	>64	2 to >64
		Levofloxacin^Citation48	>16	>16	0.25 to >16.00
		Linezolid^Citation48,Citation51,Citation52	2 to >8	>8–16, NA^Citation52	1–64
		Vancomycin^Citation52	1	NA	1
		Teicoplanin^Citation52	1	NA	≤0.5–2.0
		Daptomycin^Citation52	0.5	NA	0.5
		Tigecycline^Citation52	0.12	NA	0.12–0.25
		Quinupristin/dalfopristin^Citation52	4	NA	1–4
		Ciprofloxacin^Citation52	>4	NA	≤1 to .4
		Cotrimoxazole^Citation52	≤1	NA	≤1
		Tetracycline^Citation52	≤4	NA	≤4
		Erythromycin^Citation52	>4	NA	≤0.5 to >4.0
		Clindamycin^Citation52	>4	NA	>4
		Chloramphenicol^Citation52	>32	NA	16 to >32
		Gentamycin^Citation52	≤4	NA	≤4 to >16
		Tobramycin^Citation52	≤16	NA	≤4 to >16
		Rifampicin^Citation52	≤1	NA	≤1 to >4
S. aureus not S to vancomycin	32^Citation48	Tedizolid	0.25	1	0.12–1.00
		Cefotaxime	>64	>64	2 to >64
		Levofloxacin	16	>16	4 to >16
		Linezolid	2	4	1–4
Coagulase-negative staphylococci**	755	Tedizolid	NA	NA	0.12–0.25
		Linezolid	NA	NA	0.5–1.0
Coagulase-negative staphylococci S to linezolid *	199a,^Citation49	TR-700	0.25	0.25	≤0.03–0.50
		Linezolid	1	2	≤0.25–4.00
		Daptomycin	0.25	0.5	≤0.125–1.000
		Vancomycin	2	2	≤0.5–4.0
		Teicoplanin	2	8	≤0.5–32.0
–Coagulase-negative staphylococci S to linezolid, S to oxacillin*	41^Citation49	TR-700	0.25	0.25	0.06–0.25
		Linezolid	1	2	≤0.25–2.00
		Daptomycin	0.25	0.5	≤0.125–0.500
		Vancomycin	2	2	≤0.5–2.0
		Teicoplanin	2	4	≤0.5–8.0
–Coagulase-negative staphylococci S to linezolid, R to oxacillin*	158^Citation49	TR-700	0.125	0.25	≤0.03–0.50
		Linezolid	1	2	≤0.25–4.00
		Daptomycin	0.25	0.5	≤0.125–1.000
		Vancomycin	2	2	≤0.5–4.0
		Teicoplanin	2	8	≤0.5–32.0
Coagulase-negative staphylococci R to linezolid	5b,^Citation49	TR-700	2	NA	0.25–4.00
		Linezolid	16	NA	16–256
		Daptomycin	0.5	NA	0.25–0.50
		Vancomycin	2	NA	1–2
		Teicoplanin	4	NA	1–16
Coagulase-negative staphylococci S to methicillin	46^Citation48 + 29^Citation54	Tedizolid^Citation48,Citation54	0.25–0.50	0.5	0.12–1.0
		Cefotaxime^Citation48	0.5	2	0.03–4.00
		Levofloxacin^Citation48,Citation54	0.25–0.50	0.5	0.06–32.00
		Linezolid^Citation48,Citation54	1–2	2–4	0.5–4.0
		Erythromycin^Citation54	0.5	128	0.25 to >128.00
		Clindamycin^Citation54	0.25	1	0.12 to >128.00
		Cotrimoxazole^Citation54	0.25	16	≤0.06–32.00
		Gentamycin^Citation54	0.12	64	0.06–128.00
		Tetracycline^Citation54	0.5	32	0.5–128.0
		Oxacillin^Citation54	0.12	0.25	0.06–0.25
		Vancomycin^Citation54	1	1	0.5–2.0
Coagulase-negative staphylococci R to methicillin	58^Citation48 + 26^Citation54	Tedizolid^Citation48,Citation54	0.25–0.50	0.5	0.12–1.00
		Cefotaxime^Citation48	8	>64	0.5 to >64.0
		Levofloxacin^Citation48,Citation54	0.5–8.0	≤16	0.12 to >16.00
		Linezolid^Citation48,Citation54	1–2	2–4	0.5–8.0
		Erythromycin^Citation54	64	128	≤0.06 to >128.00
		Clindamycin^Citation54	0.25	>128	0.12 to >128.00
		Cotrimoxazole^Citation54	2	32	≤0.06–32.00
		Gentamycin^Citation54	16	64	0.06–128.00
		Tetracycline^Citation54	4	128	0.5 to >128.0
		Oxacillin^Citation54	4	64	0.5 to >128.0
		Vancomycin^Citation54	1	2	0.25–2.00
Coagulase-negative staphylococci not S to linezolid	40c,^Citation53	TR-700	4	16	1 to >32
		Vancomycin	2	2	1–2
Coagulase-negative staphylococci R to linezolid	6d,^Citation51 + 164e,^Citation52	TR-700^Citation51,Citation52	NA,^Citation51 4^Citation52	NA,^Citation51 8^Citation52	0.06–16.00
		Linezolid^Citation51,Citation52	NA,^Citation51 128^Citation52	NA,^Citation51 >128^Citation52	8 to >128
		Vancomycin^Citation52	2	4	1–4
		Teicoplanin^Citation52	4	16	≤0.5–64
		Daptomycin^Citation52	0.5	1	0.25–2.00
		Tigecycline^Citation52	0.25	0.5	≤0.06–0.50
		Quinupristin/dalfopristin^Citation52	1	2	≤0.25–16.00
		Ciprofloxacin^Citation52	>4	>4	≤1 to >4
		Cotrimoxazole^Citation52	>4	>4	≤1 to >4
		Tetracycline^Citation52	≤4	≤4	≤4 to >16
		Erythromycin^Citation52	>4	>4	≤0.5 to >4.0
		Clindamycin^Citation52	>4	>4	≤0.5 to >4.0
		Chloramphenicol^Citation52	>32	>32	≤8 to >32
		Gentamycin^Citation52	>16	>16	≤4 to >16
		Tobramycin^Citation52	>16	>16	≤4 to >16
		Rifampicin^Citation52	>4	>4	≤1 to >4
Staphylococcus epidermidis S to methicillin	48^Citation50	TR-700	0.25	0.5	0.12–1.00
		Linezolid	1	2	0.5–4.0
		Vancomycin	2	2	1–4
		Oxacillin	0.12	0.25	0.06–0.25
S. epidermidis R to methicillin	72^Citation50	TR-700	0.25	0.5	0.12–1.00
		Linezolid	1	2	0.5–4.0
		Vancomycin	2	2	0.25–4
		Oxacillin	16	>32	0.5 ≥ 32
S. epidermidis R to linezolid	19^Citation51	TR-700	4	8	2 to >64
		Linezolid	32	>128	16 to >128
Beta-hemolytic streptococci	202f,^Citation48	Tedizolid	0.25	0.25	0.12–0.5
		Cefotaxime	0.03	0.06	0.015–0.06
		Levofloxacin	0.5	1	0.25–2.00
		Linezolid	1	2	1–4
Streptococcus agalactiae	52^Citation50 + 15^Citation54	TR-700^Citation50,Citation54	0.25	0.5	0.06–1.00
		Linezolid^Citation50,Citation54	2	2	1–2
		Vancomycin^Citation50	0.5	0.5	0.25–1.00
		Penicillin G^Citation54	0.06	0.06	0.03–0.06
		Cefotaxime^Citation54	0.06	0.06	0.03–0.06
		Clindamycin^Citation54	0.25	>128	0.25 to >128.00
		Erythromycin^Citation54	0.5	>128	0.25 to >128.00
		Levofloxacin^Citation54	1	2	1–2
Streptococcus pneumoniae S to penicillin	53^Citation48 + 38^Citation50	TR-700^Citation48,Citation50	0.25	0.25	0.03–0.50
		Linezolid^Citation48,Citation50	1	1–2	0.12–2.00
		Vancomycin^Citation50	0.25	0.5	0.12–1.00
		Cefotaxime^Citation48	0.015	0.03	0.015–0.250
		Levofloxacin^Citation48	1	1	0.25–4.00
S. pneumoniae I to penicillin	26^Citation48 + 37^Citation50	TR-700^Citation48,Citation50	0.25	0.25–0.50	0.06–0.50
		Linezolid^Citation48,Citation50	1	1–2	0.5–4.0
		Vancomycin^Citation50	0.25	0.5	0.25–0.50
		Cefotaxime^Citation48	0.12	0.5	0.03–1.00
		Levofloxacin^Citation48	1	1	0.5–1.0
S. pneumoniae R to penicillin	54^Citation48 + 35^Citation50	TR-700^Citation48,Citation50	0.25	0.25	0.06–0.50
		Linezolid^Citation48,Citation50	1	1–2	0.25–2.00
		Vancomycin^Citation50	0.25	0.5	0.12–1.00
		Cefotaxime^Citation48	1	8	0.5–8.0
		Levofloxacin^Citation48	1	1	0.5–2.0
Streptococcus pyogenes	102^Citation50 + 15^Citation54	TR-700^Citation50,Citation54	0.12–0.25	0.25–0.50	0.06–0.50
		Linezolid^Citation50,Citation54	1	2	0.06–2.00
		Vancomycin^Citation50	0.5	0.5	0.25–1.00
		Penicillin G^Citation54	0.015	0.015	≤0.008–0.015
		Cefotaxime^Citation54	0.015	0.03	≤0.008–0.030
		Clindamycin^Citation54	0.12	0.25	0.12–0.25
		Erythromycin^Citation54	0.12	0.25	0.12–0.25
		Levofloxacin^Citation54	1	4	0.5–4
Streptococcus viridans	30^Citation48	Tedizolid	0.25	0.25	0.06–0.50
		Cefotaxime	0.12	0.5	0.015–2.000
		Levofloxacin	1	2	0.25–2.00
		Linezolid	2	2	0.5–2.0

Notes:

* Blood culture strains

** skin and skin-structure infection strains

a Staphylococcus epidermidis: 135, Staphylococcus hominis: 40, Staphylococcus haemolyticus: 19, Staphylococcus lugdunensis: 3, Staphylococcus intermedius: 1, Staphylococcus warneri: 1

b S. epidermidis: 2, S. hominis: 2, S. haemolyticus: 1

c Staphylococcus capitis: 2, S. epidermidis: 29, S. haemolyticus: 5, Staphylococcus simulans: 2, Staphylococcus xylosus: 2

d S. hominis: 1, Staphylococcus sciuri: 5

e S. epidermidis: 142, S. hominis: 15, S. warneri: 7

f Streptococcus agalactiae: 101, Streptococcus pyogenes: 101. In bold: Staphylococcus aureus S to linezolid* group includes 202 strains of S. aureus S to linezolid, S to oxacillin* and 247 strains of S. aureus S to linezolid, R to oxacillin*. Coagulase-negative staphylococci S to linezolid* group includes 41 strains of coagulase-negative staphylococci S to linezolid, S to oxacillin* and 158 strains of coagulase-negative staphylococci S to linezolid, R to oxacillin*. Data from Brown and Traczewski,⁴⁸ Betriu et al,⁴⁹ Schaadt et al,⁵⁰ Shaw et al,⁵¹ Rodríguez-Avial et al,⁵² Jones et al,⁵³ Yum et al,⁵⁴ Prokocimer et al.⁵⁵

Abbreviations: S, sensitive; I, intermediate sensitivity; R, resistant; NA, not applicable; MIC₅₀, minimum inhibitory concentration required to inhibit the growth of 50% of organisms; MIC₉₀, minimum inhibitory concentration required to inhibit the growth of 90% of organisms.

Table 5 Activity of tedizolid (TR-700) and other antibiotics against Gram-positive microorganisms with characterized linezolid-resistance mechanisms

Microorganism	Strains tested (n)	Antibiotic	MIC50 (mcg/mL)	MIC90 (mcg/mL)	Range (mcg/mL)
G2576T
Enterococcus spp.	69a,^Citation53	TR-700	2	2	0.5–8
		Linezolid	8	16	4–32
		Ciprofloxacin	>4	>4	1 to >4
		Daptomycin	1	2	0.12–4.00
		Erythromycin	>2	>2	≤0.25 to >2.0
		Quinupristin/dalfopristin	1	>2	≤0.25 to >2.0
		Teicoplanin	>16	>16	≤0.12 to >16.00
		Tetracycline	≤2	>8	≤2 to >8
		Vancomycin	>16	>16	0.5 to >16.0
Staphylococcus spp.	39b,^Citation53	TR-700	4	8	0.5–16.0
		Linezolid	16	>32	8 ≥ 32
		Ciprofloxacin	>4	>4	0.25 to >4.00
		Clindamycin	1	>2	≤0.25 to >2.00
		Daptomycin	0.25	0.5	0.25–1.00
		Erythromycin	>2	>2	≤0.25 to >2.00
		Gentamicin	>8	>8	≤2 to >8
		Oxacillin	>2	>2	≤0.25 to >2.00
		Quinupristin/dalfopristin	0.5	1	≤0.25–2.00
		Teicoplanin	4	8	0.5–16.0
		Tetracycline	≤2	>8	≤2 to >8
		Trimethoprim/sulfamethoxazole	>2	>2	≤0.5 to >2.0
		Vancomycin	2	2	0.5–2.0
crf gene
Staphylococcus spp.	4c,^Citation53	TR-700	1	–	0.5–8.0
		Linezolid	32	–	8 to >32
		Ciprofloxacin	>4	–	>4
		Clindamycin	>4	–	>4
		Daptomycin	≤0.25	–	≤0.25
		Erythromycin	≤0.25	–	≤0.25 to >2.00
		Gentamicin	>8	–	≤2 to >8
		Oxacillin	>2	–	>2
		Quinupristin/dalfopristin	>2	–	1 to >2
		Teicoplanin	≤2	–	≤2
		Tetracycline	≤2	–	≤2 to >8
		Trimethoprim/sulfamethoxazole	>2	–	≤0.5 to >2.0
		Vancomycin	1	–	1–2

Notes:

a Enterococcus faecalis: 15, Enterococcus faecium: 54

b Staphylococcus aureus: 6, Staphylococcus epidermidis: 22, Staphylococcus capitis: 2, Staphylococcus haemolyticus: 5, Staphylococcus simulans: 2, Staphylococcus xylosus: 2

c S. aureus: 2, S. epidermidis: 2. Data from Jones et al.⁵³

Abbreviations: MIC₅₀, minimum inhibitory concentration required to inhibit the growth of 50% of organisms; MIC₉₀, minimum inhibitory concentration required to inhibit the growth of 90% of organisms.

Table 6 Activity of tedizolid and other antibiotics against Gram-negative microorganisms

Microorganism	Strains tested (n)	Antibiotic	MIC50 (mcg/mL)	MIC90 (mcg/mL)	Range (mcg/mL)
All Haemophilus influenzae	99^Citation48 + 25^Citation54	Tedizolid^Citation48,Citation54	2–8	4–16	2–32
		Cefotaxime^Citation48,Citation54	0.015–0.030	0.5	≤0.008–2.000
		Levofloxacin^Citation48,Citation54	0.12	0.12	0.12
		Linezolid^Citation48,Citation54	≥8	>8–16	4–16
		Ampicillin^Citation54	>128	>128	0.5 to >128.0
		Ampicillin/sulbactam^Citation54	4	8	0.5–8.0
		Cefaclor^Citation54	4	>128	2 to >128
		Cefuroxime^Citation54	1	>128	0.25 to >128.0
		Azithromycin^Citation54	4	4	2–4
		Cotrimoxazol^Citation54	4	32	≤0.06–32.00
		Tetraciclina^Citation54	0.5	8	0.25–32.00
Beta-lactamase-negative H. influenzae	32^Citation48	Tedizolid	8	16	4–32
		Cefotaxime	0.008	0.015	0.008–0.030
		Levofloxacin	0.12	0.12	0.12
		Linezolid	>8	>8	4 to >8
Beta-lactamase-positive H. influenzae	42^Citation48	Tedizolid	8	32	4–32
		Cefotaxime	0.015	0.015	0.008–0.030
		Levofloxacin	0.12	0.12	0.12
		Linezolid	>8	>8	8 to >8
Beta-lactamase-negative H. influenzae, not sensitive to ampicillin	25^Citation48	Tedizolid	8	16	2–16
		Cefotaxime	0.5	0.5	0.03–2.00
		Levofloxacin	0.12	0.12	0.12
		Linezolid	>8	>8	>8 to >8
Moraxella catarrhalis	50^Citation48 + 27^Citation54	Tedizolid^Citation48,Citation54	1–4	1–4	0.5–4
		Cefotaxime^Citation48	0.250	1	0.03–2
		Levofloxacin^Citation48,Citation54	0.06	0.06	0.03–0.06
		Linezolid^Citation48,Citation54	4–8	4–8	2–16
		Penicillin G^Citation54	16	32	0.03–32
		Cefaclor^Citation54	2	8	0.25–32
		Clindamycin^Citation54	2	4	1–4
		Erythromycin^Citation54	0.25	0.5	0.12–0.5
		Tetracycline^Citation54	0.5	0.5	0.25–16

Data from Brown and Traczewski⁴⁸ and Yum et al.⁵⁴

Abbreviations: MIC₅₀, minimum inhibitory concentration required to inhibit the growth of 50% of organisms; MIC₉₀, minimum inhibitory concentration required to inhibit the growth of 90% of organisms.

Table 7 Activity of tedizolid and other antibiotics against anaerobic microorganisms

Microorganism	Strains tested (n)	Antibiotic	MIC50 (mcg/mL)	MIC90 (mcg/mL)	Range (mcg/mL)
Bacteroides fragilis	10^Citation50 + 30^Citation54	TR-700^Citation50,Citation54	2–4	2–4	1–4
		Linezolid^Citation50,Citation54	4	4	2–4
		Metronidazole^Citation50,Citation54	0.12–4.00	1–4	0.12 to >32.00
		Imipenem^Citation50,Citation54	0.12–0.25	0.5–1.0	≤0.06–4.00
		Ampicillin^Citation54	32	>128	16 to >128
		Ampicillin/sulbactam^Citation54	2	16	1–32
		Piperacillin^Citation54	32	256	4 to >256
		Piperacillin/tazobactam^Citation54	0.25	1	0.12–8.00
		Cefoxitin^Citation54	8	32	4–64
		Cefotetan^Citation54	8	32	4–128
		Clindamycin^Citation54	128	>128	≤0.06 to >128.00
Bacteroides vulgatus	10^Citation50	TR-700	2	4	1–8
		Linezolid	2	4	2–4
		Metronidazole	0.25	0.25	0.12–0.50
		Imipenem	0.25	0.5	0.25–0.50
Bacteroides thetaiotaomicron	10^Citation50 + 15^Citation54	TR-700^Citation50,Citation54	2	2	1–2
		Linezolid^Citation50,Citation54	4	4–8	4–8
		Metronidazole^Citation50,Citation54	1–4	1–4	0.5 to >32
		Imipenem^Citation50,Citation54	0.25–0.50	1–2	0.12–4
		Ampicillin^Citation54	32	>128	16 to >128
		Ampicillin/sulbactam^Citation54	1	32	1–32
		Piperacillin^Citation54	32	>256	16 to >256
		Piperacillin/tazobactam^Citation54	4	8	2–16
		Cefoxitin^Citation54	16	32	16–32
		Cefotetan^Citation54	128	>128	32 to >128
		Clindamycin^Citation54	8	>128	2 to >128
Bacteroides ovatus	10^Citation50	TR-700	2	8	0.06–8.00
		Linezolid	8	8	0.5–8.0
		Metronidazole	1	1	0.5 to >32.0
		Imipenem	0.25	0.5	0.06–0.50
Clostridium perfringens	10^Citation50 + 15^Citation54	TR-700^Citation50,Citation54	0.25–0.50	0.25–2.0	0.12–2.00
		Linezolid^Citation50,Citation54	2	2–4	1–2
		Metronidazole^Citation50,Citation54	1–4	4 to >32	1 to >32
		Imipenem^Citation50,Citation54	≤0.06–0.12	≤0.06–0.50	≤0.06–1.00
		Ampicillin^Citation54	≤0.06	0.12	≤0.06–0.50
		Ampicillin/sulbactam^Citation54	≤0.06	0.25	≤0.06–0.50
		Piperacillin^Citation54	≤0.06	0.25	≤0.06–1.00
		Piperacillin/tazobactam^Citation54	≤0.06	≤0.06	≤0.06
		Cefoxitin^Citation54	0.5	1	0.25–1.00
		Cefotetan^Citation54	≤0.06	0.12	≤0.06–0.50
		Clindamycin^Citation54	1	2	≤0.06–2.00
		Vancomycin^Citation54	0.5	0.5	0.5–2.0
Peptostreptococcus spp.	59a,^Citation54	Tedizolid	0.06	0.25	0.03–0.25
		Linezolid	0.5	1	0.25–2.00
		Ampicillin	0.12	1	≤0.06–16.00
		Ampicillin/sulbactam	0.12	1	≤0.06–8.00
		Piperacillin	≤0.06	8	≤0.06–16.00
		Piperacillin/tazobactam	≤0.06	8	≤0.06–16.00
		Cefoxitin	0.25	4
		Cefotetan	0.5	16	≤0.06–128.00
		Imipenem	≤0.06	0.12	≤0.06–1.00
		Clindamycin	0.5	64	≤0.06 to >128.00
		Metronidazole	1	2	≤0.06–4.00
		Vancomycin	0.25	0.5	≤0.12–1.00
Peptostreptococcus anaerobius	10^Citation50	TR-700	0.25	0.5	0.12–0.50
		Linezolid	1	2	0.5–8
		Metronidazole	0.5	1	≤0.06–1.00
		Imipenem	0.06	1	≤0.03–1.00
Peptostreptococcus micros	10^Citation50	TR-700	0.25	0.5	0.12–1.00
		Linezolid	1	2	0.5–2.0
		Metronidazole	≤0.06	>32	≤0.06 to >32.00
		Imipenem	≤0.03	≤0.03	≤0.03 to ≤0.06
Porphyromonas asaccharolytica	10^Citation50	TR-700	0.25	0.5	0.25–0.50
		Linezolid	1	2	0.5–2
		Metronidazole	1	1	0.5–2
		Imipenem	>0.03	0.06	≤0.03 to ≤0.06
Prevotella spp.	20^Citation50	TR-700	1	4	≤0.06–16.00
		Linezolid	2	4	0.25–16.00
		Metronidazole	0.5	>32	≤0.06 to >32.00
		Imipenem	≤0.06	1	≤0.03–16.00

Notes:

a Finegoldia magna: 19, Peptoniphilus asaccharolyticus: 15, Peptostreptococcus anaerobius: 12, Peptostreptococcus micros: 7, Anaerococcus prevotii: 6. Data from Schaadt et al⁵⁰ and Yum et al.⁵⁴

Abbreviations: MIC₅₀, minimum inhibitory concentration required to inhibit the growth of 50% of organisms; MIC₉₀, minimum inhibitory concentration required to inhibit the growth of 90% of organisms.

Table 8 Most common treatment-emergent adverse events (>2% of treated subjects) (N = 188)⁴⁰

Adverse effect(s)	N (%)
Any adverse effect	130 (69.1)
Cardiac disorders	4 (2.1)
Tachycardia	4 (2.1)
Gastrointestinal disorders	71 (37.8)
Diarrhea	16 (8.5)
Dry mouth	4 (2.1)
Nausea	35 (18.6)
Vomiting	19 (10.1)
General disorders and administration site conditions	15 (8.0)
Fatigue	5 (2.7)
Pain	6 (3.2)
Infections	41 (21.8)
Abscesses	22 (11.7)
Cellulitis	4 (2.1)
Skin infections	8 (4.3)
Investigations	8 (4.3)
Increase in blood pressure	7 (3.7)
Metabolism and nutrition disorders	6 (3.2)
Decreased appetite	5 (2.7)
Central nervous system disorders	30 (16.0)
Dizziness	5 (2.7)
Headache	21 (11.2)
Psychiatric disorders	16 (8.5)
Insomnia	6 (3.2)
Respiratory disorders	15 (8.0)
Flu	5 (2.7)
Oropharyngeal pain	4 (2.1)
Rhinorrhea	4 (2.1)
Skin and subcutaneous tissue disorders	21 (11.2)
Pruritus	4 (2.1)
Rash	5 (2.7)
Skin lesions	7 (3.7)

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