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

Tedizolid (Sivextro) for Acute Bacterial Skin and Skin Structure Infections

Tedizolid 200 mg once daily for 6 days is the FDA-approved regimen for treating ABSSSI in patients 12 years and older, offering non-inferior efficacy to linezolid 600 mg twice daily for 10 days with the advantages of shorter treatment duration, once-daily dosing, and fewer gastrointestinal side effects. 1, 2

FDA-Approved Dosing and Administration

The standard dose is 200 mg administered once daily for exactly 6 days, available as either oral tablets or intravenous infusion. 1

• Oral administration: 200 mg once daily with or without food for 6 days 1
• Intravenous administration: 200 mg infused over 1 hour once daily for 6 days 1
• No dose adjustment is required when switching from IV to oral formulation 1
• If a dose is missed: Take as soon as possible if more than 8 hours remain before the next scheduled dose; otherwise, skip and wait for the next scheduled dose 1

Approved Indications

Tedizolid is specifically FDA-approved for ABSSSI caused by susceptible Gram-positive organisms, including MRSA, MSSA, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group, and Enterococcus faecalis. 1

The FDA definition of ABSSSI includes: 3

• Cellulitis/erysipelas with lesion area ≥75 cm² (measured by redness, edema, or induration)
• Major cutaneous abscesses
• Wound infections

Clinical Context for Use

Tedizolid represents an effective treatment option for moderate to severe purulent and nonpurulent SSTIs, particularly when MRSA coverage is required. 4

Specific Clinical Scenarios:

• Purulent SSTIs with systemic signs: Fever, tachycardia, or abnormal white blood cell count where MRSA is suspected or confirmed 4
• 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 4
• Alternative to vancomycin or linezolid: For hospitalized patients requiring IV MRSA coverage, with advantages of once-daily dosing and shorter treatment duration 4

Comparative Efficacy Evidence

Two pivotal Phase III trials (ESTABLISH-1 and ESTABLISH-2) demonstrated that tedizolid 200 mg once daily for 6 days was non-inferior to linezolid 600 mg twice daily for 10 days. 2, 5

Key Trial Results:

• ESTABLISH-2: Early clinical response (≥20% lesion reduction at 48-72 hours) was 85% for tedizolid vs 83% for linezolid (difference 2.6%, 95% CI -3.0 to 8.2) 2
• ESTABLISH-1: Early clinical response was 79.5% for tedizolid vs 79.4% for linezolid (difference 0.1%, 95% CI -6.1% to 6.2%) 5
• Post-therapy evaluation: Investigator-assessed clinical success rates were 85.5% for tedizolid vs 86.0% for linezolid 5
• Lower-extremity infections: Both drugs showed comparable efficacy, with post-therapy response rates of 86.3% for tedizolid vs 87.2% for linezolid 6

Safety Profile and Advantages

Tedizolid demonstrated fewer gastrointestinal adverse events compared to linezolid (16% vs 20%), with less frequent treatment discontinuation. 2

Key Safety Advantages:

• Reduced GI toxicity: Nausea and other gastrointestinal events occur less frequently than with linezolid 2, 7
• Lower thrombocytopenia risk: Fewer low platelet counts observed compared to linezolid 6, 7
• Fewer drug interactions: May have reduced interactions with selective serotonin reuptake inhibitors or monoamine oxidase inhibitors compared to linezolid 7
• Treatment discontinuation: Only 1 patient (<1%) discontinued tedizolid vs 4 patients (1%) with linezolid in ESTABLISH-2 2

IV Preparation and Administration (Critical Details)

For IV administration, tedizolid must be reconstituted with Sterile Water for Injection and diluted only with 0.9% Sodium Chloride Injection. 1

Preparation Steps:

1. Reconstitute: Add 4 mL Sterile Water for Injection to the 200 mg vial; gently swirl (avoid vigorous shaking to minimize foaming) 1
2. Dilute: Extract 4 mL of reconstituted solution and inject into 250 mL bag of 0.9% Sodium Chloride Injection 1
3. Storage: Total time from reconstitution to administration must not exceed 24 hours at room temperature or refrigeration (2°C to 8°C) 1
4. Infusion: Administer over exactly 1 hour; do not give as IV push or bolus 1

Critical Incompatibilities:

• Incompatible with solutions containing divalent cations (Ca²⁺, Mg²⁺): Do not use Lactated Ringer's or Hartmann's Solution 1
• Do not mix with other drugs during administration 1

Common Pitfalls and Caveats

The 6-day treatment duration is fixed and should not be extended unless clinically indicated by treatment failure, as prolonged courses increase resistance risk and adverse effects. 3

• Age restriction: Only approved for patients ≥12 years of age 1
• Not for pneumonia: Like other oxazolidinones, tedizolid should not be used for pulmonary infections 8
• Single-dose vials: Contain no preservatives; discard any unused portion 1
• Resistance monitoring: Should only be used for proven or strongly suspected bacterial infections to reduce development of drug-resistant bacteria 1
• Duration principles: Antibiotics can be discontinued once clinical signs and symptoms resolve; there is no evidence supporting continuation until complete wound healing 3