Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

Figures & data

Figure 1 Chemical structure of oritavancin.

Table 1 Susceptibility of aerobic and anaerobic Gram-positive bacteria to oritavancin

Organism	Number of isolates	MIC range (μg/mL)	MIC50 (μg/mL)	MIC90 (μg/mL)
Susceptibility of aerobic Gram-positive bacteria to oritavancin^Citation12,Citation13
Methicillin-susceptible Staphylococcus aureus	7,332	≤0.004–0.50	0.03	0.06
Methicillin-resistant Staphylococcus aureus	4,264	≤0.004–0.25	0.03	0.06
Staphylococcus epidermidis	586	≤0.008–0.5	0.03–0.06	0.06–0.12
Enterococcus faecalis	1,017	≤0.004–0.5	0.015–0.03	0.06
Vancomycin-susceptible Enterococcus faecium	278	≤0.004–0.03	≤0.008	≤0.008–0.015
Vancomycin-resistant Enterococcus faecium	216	≤0.004–0.5	0.008–0.06	0.06–0.12
Streptococcus anginosus group	172	≤0.008–0.06	≤0.008	≤0.008–0.015
Streptococcus pyogenes	868	≤0.0005–1.0	0.03	0.03–0.25
Streptococcus agalactiae	546	0.001–0.5	0.03	0.12
Streptococcus dysgalactiae	81	≤0.008–0.5	0.06	0.25–0.5
Susceptibility of anaerobic Gram-positive bacteria to oritavancin^Citation11
Clostridium perfringens	28	0.25–1	0.5	1.0
Propionibacterium acnes	11	0.125–0.25	0.125	0.25
Peptostreptococcus anaerobius	15	0.06–0.5	0.125	0.25
Peptoniphilus asaccharolyticus	17	≤0.03–0.5	0.25	0.5
Anaerococcus prevotti	16	≤0.03–1	≤0.03	0.25
Micromonas micros	15	≤0.03–0.5	0.125	0.25

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

Table 2 Susceptibility of Gram-positive bacteria to oritavancin and selected antibiotics in different geographic regions

Organism	Antimicrobial agent	MIC90 (μg/mL)
		USA	Europe	Canada
Methicillin-resistant Staphylococcus aureus	Oritavancin	0.06	0.06	0.06
	Vancomycin	1	1	1
	Daptomycin	0.5	0.5	0.5
Coagulase-negative staphylococci	Oritavancin	0.06	0.06	0.12 (Staphylococcus epidermidis)
	Vancomycin	2	2	2 (S. epidermidis)
	Daptomycin	0.5	0.5	0.25 (S. epidermidis)
Enterococcus faecalis	Oritavancin	0.06	0.06	0.06
	Vancomycin	2	2	2
	Daptomycin	2	1	2
Vancomycin-susceptible Enterococcus faecium	Oritavancin	≤0.008	≤0.008	0.015
	Vancomycin	2	1	1
	Daptomycin	4	4	2
Vancomycin-resistant Enterococcus faecium	Oritavancin	0.12	0.06	0.12
	Vancomycin	>16	>16	>32
	Daptomycin	2	4	2
Streptococcus agalactiae	Oritavancin	0.12	0.12	0.12
	Vancomycin	0.5	0.5	0.5
	Daptomycin	0.25	0.25	0.25
Streptococcus pyogenes	Oritavancin	0.12	0.12	0.25
	Vancomycin	0.5	0.5	0.5
	Daptomycin	≤0.06	≤0.06	0.12
Streptococcus anginosus group	Oritavancin	0.015	≤0.008	NR
	Vancomycin	1	1	NR
	Daptomycin	0.5	0.5	NR

Notes: Data from Mendes et al¹² and Karlowsky et al.¹³

Abbreviations: MIC90, minimum inhibitory concentration required to inhibit the growth of 90% of isolate; NR, not reported.

Table 3 Pharmacokinetic parameters of oritavancin in Phase II/III studies (n=360)

Pharmacokinetic parameter	Mean value (SD)
Cmax (μg/mL)	28.5 (12.2)
Cmin (μg/mL)	1.99 (1.10)
AUC0–24 (μg h/mL)	146 (63.7)
T1/2β (hours)	31.2 (11.4)
T1/2γ (hours)	393 (73.5)
CL (L/h)	0.601 (0.204)
Vc (L)	7.10 (2.46)

Notes: Data from Rubino et al.¹⁷

Abbreviations: SD, standard deviation; C_max, maximum plasma concentration; C_min, minimum plasma concentration; AUC_0–24, area under the plasma concentration–time curve from time 0 hours to 24 hours; T_1/2β, plasma elimination-phase half-life; T_1/2γ, plasma terminal elimination half-life; CL, total clearance; V_c, volume of distribution of the central compartment.

Table 4 Oritavancin Phase III clinical trials

	SOLO I^Citation31			SOLO II^Citation32
	Oritavancin	Vancomycin	Difference [95% CI]	Oritavancin	Vancomycin	Difference [95% CI]
Primary and secondary end points for mITT population
Primary composite end point	82.3% (391/475)	78.9% (378/479)	3.4 [−1.6, 8.4]	80.1% (403/503)	82.9% (416/502)	−2.7% [−7.5, 2.0]
≥20% reduction in lesion size	86.9% (413/475)	82.9% (397/479)	4.1 [−0.5, 8.6]	85.9% (432/503)	85.3% (428/502)	0.6 [−3.7, 5.0]
Clinical cure	79.6% (378/475)	80.0% (383/479)	−0.4 [−5.5, 4.7]	82.7% (416/503)	80.5% (404/502)	2.2 [−2.6, 7.0]
Primary and secondary end points for CE population
Primary composite end point	87.3% (344/394)	86.1% (342/397)	1.2 [−3.6, 5.9]	83.6% (357/427)	87.7% (358/408)	−4.1 [−8.9, 6]
≥20% reduction in lesion size	91.9% (362/394)	93.2% (370/397)	−1.3 [−5.0, 2.3]	88.5% (378/427)	89.2% (364/408)	−0.7 [−5.0, 3.6]
Clinical cure	90.6% (357/394)	88.7% (352/397)	1.9 [−2.3, 6.2]	93.2% (398/427)	94.9% (387/408)	−1.6 [−4.9, 1.6]
Primary efficacy outcome at early clinical evaluation according to pathogen detected at baseline
Detection of at least one pathogen	82.4% (201/244)	81.0% (196/242)	1.4 [−5.5, 8.3]	82.1% (234/285)	85.1% (252/296)	−3.0 [−9.0, 3.0]
Staphylococcus aureus	81.8% (180/220)	81.9% (172/210)	−0.1 [−7.4, 7.2]	83.2% (208/250)	84.9% (219/258)	−1.7 [−8.1, 4.7]
MRSA	80.8% (84/104)	80.0% (80/100)	0.8 [−10.1, 11.7]	82.0% (82/100)	81.2% (82/101)	0.8 [−9.9, 11.5]
MSSA	82.8% (96/116)	83.6% (92/110)	−0.9 [−10.6, 8.9]	84.0% (126/150)	87.3% (137/157)	−3.3 [−11.1, 4.6]
Enterococcus faecalis	85.7% (6/7)	80.0% (4/5)	NA	83.3% (5/6)	85.7% (6/7)	NA

Abbreviations: CI, confidence interval; mITT, modified intention to treat; CE, clinical evaluation; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible S. aureus; NA, not available.

Table 5 Adverse events attributed to oritavancin compared to vancomycin in Phase III trials

Frequently reported adverse events	Oritavancin	Vancomycin
	SOLO I + SOLO II (n=976)	SOLO I + SOLO II (n=983)
Nausea	9.9% (97/976)	10.5% (103/983)
Headache	7.1% (69/976)	6.7% (66/983)
Pruritus	3% (29/976)	7.4% (73/983)
Vomiting	4.6% (45/976)	4.7% (46/983)
Constipation	3.4% (33/976)	3.9% (38/983)
Diarrhea	3.7% (36/976)	3.3% (32/983)
Cellulitis	3.8% (37/976)	3.3% (32/983)
Infusion-site extravasation	3.4% (33/976)	3.4% (33/983)
Pyrexia	3.1% (30/976)	3.2% (31/983)
Abscess on limb	2.8% (27/976)	1.3% (13/983)
Dizziness	2.7% (26/976)	2.6% (26/983)
Infusion-site phlebitis	2.5% (24/976)	1.5% (15/983)
Infusion-site reaction	1.9% (19/976)	3.5% (34/983)
Insomnia	1.4% (14/976)	1.3% (13/983)
Chills	1% (10/976)	1.2% (12/983)
Fatigue	1% (10/976)	0.6% (6/983)
Urticaria	0.7% (7/976)	1.5% (15/983)
Alanine aminotransferase elevation	2.8% (27/976)	1.5% (15/983)
Aspartate aminotransferase elevation	1.1% (11/976)	1.1% (11/983)

Notes: Data from Corey et al³¹ and Corey et al.³²

Table 6 Some intravenous antibiotics for acute bacterial skin and skin structure infections in adults

Drug	Usual adult dose	Cost of 7-day therapya
Vancomycin	15–20 mg/kg (max 2 g) q 12 hours ×7–14 daysb	$115.50
Dalbavancin	1,000 mg ×1, then 500 mg 1 week later	$2,980.00c
Oritavancin	1,200 mg once	$2,900.00d
Televancin	10 mg/kg q 24 hours ×7–14 daysb	$2,166.50
Linezolid	600 mg q 12 hours ×10–14 days	$1,952.30
Tedizolid	200 mg q 24 hours ×6 days	$1,410.00
Ceftaroline	600 mg q 12 hours ×5–14 daysb	$1,768.90
Daptomycin	4 mg/kg q 24 hours ×7–14 daysb	$2,482.90e

Notes:

a Approximate wholesale acquisition cost for 7-day treatment of a 70 kg patient with the lowest usual dosage;

b dosage adjustment may be needed for renal or hepatic impairment;

c cost for two 500 mg vials;

d cost for three 400 mg vials;

e cost for one 500 mg vial. Data from The Medical Letter, Inc..²

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