What is the recommended use and dosage of Oritavancin (oritavancin) for treating acute bacterial skin and skin structure infections?

Oritavancin for Acute Bacterial Skin and Skin Structure Infections

Oritavancin is administered as a single 1,200 mg intravenous infusion over 3 hours for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive pathogens, including MRSA. 1

FDA-Approved Indication and Dosing

• Single-dose regimen: 1,200 mg IV infusion over 3 hours 1, 2
• No dosage adjustment required for patients with mild to moderate hepatic or renal impairment 2
• No therapeutic drug monitoring needed due to predictable pharmacokinetics 2

Clinical Efficacy

Oritavancin demonstrated non-inferiority to vancomycin (1 g or 15 mg/kg every 12 hours for 7-10 days) across multiple endpoints in two large phase 3 trials (SOLO I and SOLO II). 1, 3

Primary Efficacy Outcomes:

• Early clinical response (48-72 hours): 82.3% vs 78.9% (Trial 1) and 80.1% vs 82.9% (Trial 2) for oritavancin vs vancomycin 1
• ≥20% reduction in lesion area (48-72 hours): 86.9% vs 82.9% (Trial 1) and 85.9% vs 85.3% (Trial 2) 1
• Clinical cure at 7-14 days post-treatment: 82.7% vs 80.5% 3

Pathogen Coverage:

• Highly effective against MRSA with clinical response rates similar to vancomycin in 405 patients with confirmed MRSA infection 4
• Potent in vitro activity: MIC90 of 0.12 µg/mL for S. aureus, 0.25 µg/mL for S. pyogenes, and 0.06 µg/mL for E. faecalis 4
• Effective against both methicillin-susceptible and methicillin-resistant S. aureus, including strains with the Panton-Valentine leukocidin gene 4

Clinical Applications

Appropriate Patient Populations:

• Adults with ABSSSI including cellulitis/erysipelas (40%), wound infections (29%), and major cutaneous abscesses (31%) 1
• Outpatient treatment to avoid hospitalization: Real-world data showed only 6.1% all-cause admission rate within 30 days when used in outpatient infusion centers 5
• Early hospital discharge: 6.6% all-cause and 2.6% infection-related 30-day readmission rates when used at hospital discharge 5

Infection Types Treated:

• Cellulitis and erysipelas 1
• Wound infections 1
• Major cutaneous abscesses 1
• Off-label multidose use: Osteomyelitis (54.4% of cases) with 85% clinical cure/improvement, though this requires multiple doses beyond FDA approval 6

Safety Profile

Oritavancin was generally well tolerated with most adverse events being mild in severity. 2

Common Adverse Events:

• Nausea, headache, vomiting (most frequent) 2
• Limb and subcutaneous abscesses 2
• Diarrhea 2
• Infusion-related reactions and hypoglycemia in multidose regimens 6

Important Laboratory Considerations:

• Positive indirect antiglobulin test (IAT): Occurred in 66% of subjects at 15 days post-dose, though no hemolysis was reported 1
• May interfere with blood cross-matching for up to 15 days after administration 1
• Low-level anti-oritavancin antibodies detected in 17% of subjects, but no clinically significant effects on safety or efficacy 1

Clinical Advantages

The single-dose regimen offers substantial practical benefits over traditional multi-day IV therapy. 2

• Eliminates compliance concerns with single administration 2
• Reduces healthcare resource utilization and costs: Mean 30-day healthcare costs of $3,698 in outpatient setting 5
• Shortens or eliminates hospital stays 2, 5
• Long terminal half-life (~393 hours) provides sustained therapeutic levels 6

Positioning in Treatment Guidelines

While oritavancin is not specifically mentioned in the 2018 WSES/SIS-E consensus guidelines, it fits within the category of newer IV agents for MRSA coverage in SSTI alongside dalbavancin and tedizolid. 7 The guidelines recommend 7-14 days of therapy individualized based on clinical response for MRSA SSTI 7, though oritavancin's single-dose regimen represents a departure from this traditional approach with proven non-inferiority 1.

Critical Caveats

• Not approved for diabetic foot infections: FDA guidance specifically excludes lower extremity infections in neurologically compromised patients 7
• Concomitant aztreonam or metronidazole may be needed if Gram-negative or anaerobic coverage is required 1
• Multidose regimens (1,200 mg initial dose followed by 800-1,200 mg subsequent doses) are used off-label for osteomyelitis and other infections requiring prolonged therapy, but lack FDA approval 6