What is the recommended use and dosage of Tedizolid (Sivextro) for treating acute bacterial skin and skin structure infections (ABSSSI)?

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

Tedizolid is administered as 200 mg once daily for 6 days, available in both oral and intravenous formulations, and represents a highly effective first-line option for treating ABSSSI caused by Gram-positive organisms including MRSA. 1

Approved Indications and Dosing

Standard Dosing Regimen:

• 200 mg once daily for exactly 6 days for patients 12 years and older 1
• Available as both oral tablets (taken with or without food) and IV infusion 1
• IV formulation requires 1-hour infusion time 1
• No dose adjustment needed when switching between IV and oral routes 1

Approved Pathogens:

• Staphylococcus aureus (both MRSA and MSSA) 1
• Streptococcus pyogenes, S. agalactiae, and Streptococcus anginosus Group 1
• Enterococcus faecalis 1

Clinical Context and Positioning

Tedizolid receives the highest level recommendation (1A) from international guidelines for both oral and IV treatment of MRSA skin and soft tissue infections. 2 This places it on equal footing with linezolid and daptomycin as a preferred agent.

When to Use Tedizolid:

• Moderate to severe purulent or nonpurulent SSTIs requiring MRSA coverage 3
• Purulent SSTIs with systemic signs (fever, tachycardia, elevated WBC) where MRSA is suspected or confirmed 3
• Severe nonpurulent cellulitis/erysipelas in patients who failed oral antibiotics, have systemic signs, are immunocompromised, or show signs of deeper infection 3
• As an alternative to vancomycin or linezolid for hospitalized patients, with advantages of once-daily dosing and shorter treatment duration 3

Comparative Efficacy

Tedizolid demonstrates non-inferior efficacy to linezolid but with a shorter treatment course (6 days vs 10 days) and once-daily dosing (vs twice-daily). 3, 4

Key Clinical Trial Results:

• Early clinical response rates at 48-72 hours: 79.5% for tedizolid vs 79.4% for linezolid 4
• Post-therapy success rates: 85.5% for tedizolid vs 86.0% for linezolid 4
• Similar efficacy across infection types: cellulitis/erysipelas, major cutaneous abscess, and wound infections 5
• Comparable outcomes for lower-extremity vs non-lower-extremity infections 6
• MRSA microbiological response: 95.2% for tedizolid vs 94% for linezolid 5

Safety and Tolerability Advantages

Tedizolid demonstrates a superior safety profile compared to linezolid, particularly regarding gastrointestinal effects and hematologic toxicity. 5, 7

Specific Advantages:

• Lower incidence of nausea and vomiting compared to linezolid 5
• Reduced risk of thrombocytopenia and neutropenia due to shorter treatment duration and less bone marrow suppression 5, 7
• Weaker MAO inhibitor activity than linezolid, suggesting fewer drug-drug interactions with SSRIs and MAOIs 8, 7
• No dosage adjustment required for any degree of renal or hepatic dysfunction 7

Practical Administration Details

IV Preparation (Critical Steps):

• Reconstitute 200 mg vial with 4 mL Sterile Water for Injection 1
• Gently swirl to dissolve; avoid vigorous shaking to minimize foaming 1
• Further dilute in 250 mL of 0.9% Sodium Chloride Injection only 1
• Do NOT use solutions containing divalent cations (Ca²⁺, Mg²⁺) such as Lactated Ringer's or Hartmann's Solution 1
• Total time from reconstitution to administration must not exceed 24 hours 1
• Administer as IV infusion only—never as IV push or bolus 1

Missed Dose Management:

• Take missed dose if more than 8 hours remain before next scheduled dose 1
• If less than 8 hours remain, skip and wait for next scheduled dose 1

Treatment Duration Considerations

The standard 6-day course of tedizolid is sufficient for most ABSSSI cases, though guidelines suggest 7-14 days for MRSA SSTIs should be individualized based on clinical response. 2 The discrepancy reflects that tedizolid's FDA approval is specifically for 6 days 1, while broader SSTI guidelines account for various agents and infection severities. For tedizolid specifically, the 6-day regimen has proven non-inferior to 10 days of linezolid 4.

Key Clinical Advantages

Four-to-eightfold greater in vitro potency against staphylococci, enterococci, and streptococci compared to linezolid, including drug-resistant phenotypes 7

High oral bioavailability (approximately 90%) enables seamless transition from IV to oral therapy without dose adjustment 7

Activity against certain linezolid-resistant strains harboring the cfr gene (in absence of specific ribosomal mutations) 7