What is the recommended dosage and treatment guidelines for Tedizolid (Sivextro) for acute bacterial skin and skin structure infections (ABSSSI)?

Tedizolid (Sivextro) Dosing and Treatment Guidelines for ABSSSI

Tedizolid is administered at 200 mg once daily for 6 days, either orally (with or without food) or as a 1-hour intravenous infusion, for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in patients 12 years and older. 1

FDA-Approved Indications

Tedizolid is specifically approved for ABSSSI caused by susceptible Gram-positive organisms including: 1

• Staphylococcus aureus (both MRSA and MSSA)
• Streptococcus pyogenes
• Streptococcus agalactiae
• Streptococcus anginosus Group
• Enterococcus faecalis

Clinical Context for Use

Tedizolid represents an effective treatment option for moderate to severe purulent and nonpurulent SSTIs, particularly when MRSA coverage is required. 2

Specific Clinical Scenarios:

• Purulent SSTIs with systemic signs (fever, tachycardia, abnormal WBC count) where MRSA is suspected or confirmed 2
• Severe nonpurulent cellulitis/erysipelas in patients who have failed oral antibiotics, have systemic signs of infection, are immunocompromised, or have clinical signs of deeper infection 2
• Hospitalized patients requiring IV MRSA coverage as an alternative to linezolid or vancomycin, with the advantage of once-daily dosing and shorter treatment duration 2

Dosing Regimen Details

Standard Dosing: 1

• Dose: 200 mg once daily
• Duration: 6 days
• Route: Either oral OR intravenous (no dose adjustment needed when switching between routes)
• Oral administration: Can be taken with or without food
• IV administration: 1-hour infusion time

Missed Dose Instructions: 1

• Take as soon as possible if more than 8 hours remain before the next scheduled dose
• If less than 8 hours remain, skip the missed dose and wait for the next scheduled dose

Comparative Efficacy Evidence

Tedizolid 200 mg once daily for 6 days demonstrated non-inferior efficacy to linezolid 600 mg twice daily for 10 days in two Phase III trials (ESTABLISH-1 and ESTABLISH-2). 2, 3, 4

Key Trial Results:

• Early clinical response (48-72 hours): 79.5% for tedizolid vs 79.4% for linezolid in ESTABLISH-1 4; 85% for tedizolid vs 83% for linezolid in ESTABLISH-2 3
• Post-therapy evaluation success: 85.5% for tedizolid vs 86.0% for linezolid 4
• Lower-extremity ABSSSI: Post-therapy response rates were comparable (87.1% tedizolid vs 86.6% linezolid for lower extremity; 86.3% tedizolid vs 87.2% linezolid for non-lower extremity) 5
• MRSA infections: Similar efficacy demonstrated in patients with documented MRSA 4

Safety Profile Advantages

Tedizolid demonstrated fewer gastrointestinal adverse events compared to linezolid. 3

• Gastrointestinal adverse events: 16% with tedizolid vs 20% with linezolid 3
• Treatment discontinuation due to adverse events: <1% with tedizolid vs 1% with linezolid 3
• May have fewer drug interactions with SSRIs and MAOIs compared to linezolid 6
• May have comparatively delayed onset of thrombocytopenia and nausea compared to linezolid 6

IV Preparation and Administration

Reconstitution: 1

1. Reconstitute 200 mg vial with 4 mL Sterile Water for Injection
2. Gently swirl (avoid vigorous shaking to minimize foaming)
3. Withdraw 4 mL of reconstituted solution
4. Dilute in 250 mL of 0.9% Sodium Chloride Injection, USP

Administration Requirements: 1

• Infusion time: 1 hour
• Route: IV infusion only (NOT IV push or bolus)
• Total time from reconstitution to administration: Maximum 24 hours (at room temperature or refrigerated at 2-8°C)
• Compatible solution: 0.9% Sodium Chloride only
• Incompatible solutions: Any solution containing divalent cations (Ca²⁺, Mg²⁺), including Lactated Ringer's and Hartmann's Solution

Important Clinical Caveats

• Single-dose vials only: Contains no preservatives; discard unused portion 1
• No dose adjustment needed: When switching from IV to oral formulation 1
• High oral bioavailability: Allows for easy oral step-down therapy 6
• Use only for proven or strongly suspected bacterial infections: To reduce development of drug-resistant bacteria 1
• Consider culture and susceptibility data: When available, use to guide or modify therapy 1